Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide

ilustraciones, graficas

Autores:: Castillo Perdomo, Diana Marcela

Tipo de recurso:: Doctoral thesis

Fecha de publicación:: 2022

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:: spa

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network_acronym_str	UNACIONAL2
network_name_str	Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
dc.title.translated.eng.fl_str_mv	Presence of RgpA, anti-RgpA antibodies and their association with rheumatoid arthritis
title	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
spellingShingle	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide 610 - Medicina y salud::616 - Enfermedades Cromatografía Artritis Reumatoide Arthritis, Rheumatoid Chromatography Porphyromonas gingivalis RgpA PPAD Gingipaínas Artritis Reumatoidea Periodontitis Gingipains Rheumatoid arthritis
title_short	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
title_full	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
title_fullStr	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
title_full_unstemmed	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
title_sort	Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide
dc.creator.fl_str_mv	Castillo Perdomo, Diana Marcela
dc.contributor.advisor.none.fl_str_mv	Castellanos Parra, Jaime Eduardo Romero Sánchez, María Consuelo
dc.contributor.author.none.fl_str_mv	Castillo Perdomo, Diana Marcela
dc.contributor.researchgroup.spa.fl_str_mv	Unidad de Investigación Básica Oral - UIBO
dc.contributor.subjectmatterexpert.none.fl_str_mv	Lafaurie Villamil Gloria Inés
dc.contributor.orcid.spa.fl_str_mv	Castillo, Diana Marcela [0000-0002-1846-7448]
dc.contributor.cvlac.spa.fl_str_mv	Castillo Perdomo, Diana Marcela [https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000293580]
dc.contributor.scopus.spa.fl_str_mv	Castillo, Diana Marcela [16300829800]
dc.contributor.researchgate.spa.fl_str_mv	Castillo, Diana Marcela [https://www.researchgate.net/profile/Diana-Castillo-4]
dc.contributor.googlescholar.spa.fl_str_mv	Castillo, Diana Marcela [https://scholar.google.com/citations?user=_DyKomkAAAAJ&hl=es]
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud::616 - Enfermedades
topic	610 - Medicina y salud::616 - Enfermedades Cromatografía Artritis Reumatoide Arthritis, Rheumatoid Chromatography Porphyromonas gingivalis RgpA PPAD Gingipaínas Artritis Reumatoidea Periodontitis Gingipains Rheumatoid arthritis
dc.subject.other.spa.fl_str_mv	Cromatografía Artritis Reumatoide
dc.subject.other.eng.fl_str_mv	Arthritis, Rheumatoid Chromatography
dc.subject.proposal.none.fl_str_mv	Porphyromonas gingivalis RgpA PPAD
dc.subject.proposal.spa.fl_str_mv	Gingipaínas Artritis Reumatoidea Periodontitis
dc.subject.proposal.eng.fl_str_mv	Gingipains Rheumatoid arthritis
description	ilustraciones, graficas
publishDate	2022
dc.date.issued.none.fl_str_mv	2022-12-02
dc.date.accessioned.none.fl_str_mv	2023-02-06T16:52:57Z
dc.date.available.none.fl_str_mv	2023-02-06T16:52:57Z
dc.type.spa.fl_str_mv	Trabajo de grado - Doctorado
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/doctoralThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.coar.spa.fl_str_mv	http://purl.org/coar/resource_type/c_db06
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TD
format	http://purl.org/coar/resource_type/c_db06
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/83320
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co
url	https://repositorio.unal.edu.co/handle/unal/83320 https://repositorio.unal.edu.co
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv	spa
language	spa
dc.relation.references.spa.fl_str_mv	Adams, B., Nunes, J. M., Page, M. J., Roberts, T., Carr, J., Nell, T. A., Kell, D. B., & Pretorius, E. (2019). Parkinson's Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens. Frontiers in aging neuroscience, 11, 210. https://doi.org/10.3389/fnagi.2019.00210 Aletaha, D., Neogi, T., Silman, A. J., Funovits, J., Felson, D. T., Bingham, C. O., 3rd, Birnbaum, N. S., Burmester, G. R., Bykerk, V. P., Cohen, M. D., Combe, B., Costenbader, K. H., Dougados, M., Emery, P., Ferraccioli, G., Hazes, J. M., Hobbs, K., Huizinga, T. W., Kavanaugh, A., Kay, J., … Hawker, G. (2010). 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and rheumatism, 62(9), 2569–2581. https://doi.org/10.1002/art.27584 Ambrosio, N., Marín, M. J., Laguna, E., Herrera, D., Sanz, M., & Figuero, E. (2019). Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients. Archives of oral biology, 98, 213–219. https://doi.org/10.1016/j.archoralbio.2018.11.025 Arévalo-Caro, C., Romero-Sánchez, C., & Garavito-Rodríguez, E. (2022). Relation between anti-Porphyromonas gingivalis antibody titers and HLA-DRB1 neutral alleles in individuals with rheumatoid arthritis. Acta odontologica Scandinavica, 80(2), 131–139. https://doi.org/10.1080/00016357.2021.1959053 Azzi, L., Rania, S., Vinci, R., Spadari, F., Croveri, F., Scognamiglio, C., Farronato, D., Tettamanti, L., Tagliabue, A., Silvestre-Rangil, J., & Bellintani, C. (2017). Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. Journal of biological regulators and homeostatic agents, 31(2 Suppl 1), 97–103. Bae, S. C., & Lee, Y. H. (2018). Association between anti-Porphyromonas gingivalis antibody, anti-citrullinated protein antibodies, and rheumatoid arthritis: A meta-analysis. Zeitschrift fur Rheumatologie, 77(6), 522–532. https://doi.org/10.1007/s00393-017-0328-y Bello-Gualtero, J. M., Lafaurie, G. I., Hoyos, L. X., Castillo, D. M., De-Avila, J., Munevar, J. C., Unriza, S., Londoño, J., Valle-Oñate, R., & Romero-Sánchez, C. (2016). Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross-Sectional Study. Journal of periodontology, 87(4), 346–356. https://doi.org/10.1902/jop.2015.150455 Bender, P., Bürgin, W. B., Sculean, A., & Eick, S. (2017). Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis. Clinical oral investigations, 21(1), 33–42. https://doi.org/10.1007/s00784-016-1938-5 Bereta, G., Goulas, T., Madej, M., Bielecka, E., Solà, M., Potempa, J., & Xavier Gomis-Rüth, F. (2019). Structure, function, and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase. Protein science: a publication of the Protein Society, 28(3), 478–486. https://doi.org/10.1002/pro.3571 Bıyıkoğlu, B., Buduneli, N., Aksu, K., Nalbantsoy, A., Lappin, D. F., Evrenosoğlu, E., & Kinane, D. F. (2013). Periodontal therapy in chronic periodontitis lowers gingival crevicular fluid interleukin-1beta and DAS28 in rheumatoid arthritis patients. Rheumatology international, 33(10), 2607–2616. https://doi.org/10.1007/s00296-013-2781-5 Bonfim, M., Mattos, F. F., Ferreira e Ferreira, E., Campos, A. C., & Vargas, A. M. (2013). Social determinants of health and periodontal disease in Brazilian adults: a cross-sectional study. BMC oral health, 13, 22. https://doi.org/10.1186/1472-6831-13-22 Borgnakke W. S. (2015). Does Treatment of Periodontal Disease Influence Systemic Disease?. Dental clinics of North America, 59(4), 885–917. https://doi.org/10.1016/j.cden.2015.06.007 Botero, J. E., Contreras, A., Lafaurie, G., Jaramillo, A., Betancourt, M., & Arce, R. M. (2007). Occurrence of periodontopathic and superinfecting bacteria in chronic and aggressive periodontitis subjects in a Colombian population. Journal of periodontology, 78(4), 696–704. https://doi.org/10.1902/jop.2007.060129 Boutaga, K., van Winkelhoff, A. J., Vandenbroucke-Grauls, C. M., & Savelkoul, P. H. (2003). Comparison of real-time PCR and culture for detection of Porphyromonas gingivalis in subgingival plaque samples. Journal of clinical microbiology, 41(11), 4950–4954. https://doi.org/10.1128/JCM.41.11.4950-4954.2003 Cantley, M. D., Haynes, D. R., Marino, V., & Bartold, P. M. (2011). Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. Journal of clinical periodontology, 38(6), 532–541. https://doi.org/10.1111/j.1600-051X.2011.01714.x Castillo-Cañón, J. C., Trujillo-Cáceres, S. J., Bautista-Molano, W., Valbuena-García, A. M., Fernández-Ávila, D. G., & Acuña-Merchán, L. (2021). Rheumatoid arthritis in Colombia: a clinical profile and prevalence from a national registry. Clinical rheumatology, 40(9), 3565–3573. https://doi.org/10.1007/s10067-021-05710-x Castillo, D. M., Castillo, Y., Delgadillo, N. A., Neuta, Y., Lafaurie, G. I., Romero-Sánchez, C., & Castellanos, J. E. (2022). Purification of RgpA from external outer membrane vesicles of Porphyromonas gingivalis. Anaerobe, 77, 102647. https://doi.org/10.1016/j.anaerobe.2022.102647 Castillo, Y., Castellanos, J. E., Lafaurie, G. I., & Castillo, D. M. (2022). Porphyromonas gingivalis outer membrane vesicles modulate cytokine and chemokine production by gingipain-dependent mechanisms in human macrophages. Archives of oral biology, 140, 105453. https://doi.org/10.1016/j.archoralbio.2022.105453 Ciesielski, O., Biesiekierska, M., Panthu, B., Soszyński, M., Pirola, L., & Balcerczyk, A. (2022). Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives. Cellular and molecular life sciences: CMLS, 79(2), 94. https://doi.org/10.1007/s00018-022-04126-3 Chang, K., Yang, S. M., Kim, S. H., Han, K. H., Park, S. J., & Shin, J. I. (2014). Smoking and rheumatoid arthritis. International journal of molecular sciences, 15(12), 22279–22295. https://doi.org/10.3390/ijms151222279 Chaparro-Sanabria, J. A., Bautista-Molano, W., Bello-Gualtero, J. M., Chila-Moreno, L., Castillo, D. M., Valle-Oñate, R., Chalem, P., & Romero-Sánchez, C. (2019). Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first-degree relatives. International journal of rheumatic diseases, 22(11), 1990–2000. https://doi.org/10.1111/1756-185X.13724 Chapple, I., Mealey, B. L., Van Dyke, T. E., Bartold, P. M., Dommisch, H., Eickholz, P., Geisinger, M. L., Genco, R. J., Glogauer, M., Goldstein, M., Griffin, T. J., Holmstrup, P., Johnson, G. K., Kapila, Y., Lang, N. P., Meyle, J., Murakami, S., Plemons, J., Romito, G. A., Shapira, L., … Yoshie, H. (2018). Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Journal of periodontology, 89 Suppl 1, S74–S84. https://doi.org/10.1002/JPER.17-0719 Chen, Y. W., Nagasawa, T., Wara-Aswapati, N., Ushida, Y., Wang, D., Takeuchi, Y., Kobayashi, H., Umeda, M., Inoue, Y., Iwai, T., Ishikawa, I., & Izumi, Y. (2009). Association between periodontitis and anti-cardiolipin antibodies in Buerger disease. Journal of clinical periodontology, 36(10), 830–835. https://doi.org/10.1111/j.1600-051X.2009.01467.x Chen, Z., Potempa, J., Polanowski, A., Wikstrom, M., & Travis, J. (1992). Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. The Journal of biological chemistry, 267(26), 18896–18901. Chiang, H. I., Li, J. R., Liu, C. C., Liu, P. Y., Chen, H. H., Chen, Y. M., Lan, J. L., & Chen, D. Y. (2019). An Association of Gut Microbiota with Different Phenotypes in Chinese Patients with Rheumatoid Arthritis. Journal of clinical medicine, 8(11), 1770. https://doi.org/10.3390/jcm8111770 Chou, Y. Y., Lai, K. L., Chen, D. Y., Lin, C. H., & Chen, H. H. (2015). Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide, Population-Based Cohort Study. PloS one, 10(10), e0139693. https://doi.org/10.1371/journal.pone.0139693 Crowe, J., Masone, B. S., & Ribbe, J. (1995). One-step purification of recombinant proteins with the 6xHis tag and Ni-NTA resin. Molecular biotechnology, 4(3), 247–258. https://doi.org/10.1007/BF02779018 Cush J. J. (2021). Rheumatoid Arthritis: Early Diagnosis and Treatment. The Medical clinics of North America, 105(2), 355–365. https://doi.org/10.1016/j.mcna.2020.10.006 Curtis, M. A., Kuramitsu, H. K., Lantz, M., Macrina, F. L., Nakayama, K., Potempa, J., Reynolds, E. C., & Aduse-Opoku, J. (1999). Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis. Journal of periodontal research, 34(8), 464–472. https://doi.org/10.1111/j.1600-0765.1999.tb02282.x Darrah, E., & Andrade, F. (2018). Rheumatoid arthritis and citrullination. Current opinion in rheumatology, 30(1), 72–78. https://doi.org/10.1097/BOR.0000000000000452 Dashper, S. G., Mitchell, H. L., Seers, C. A., Gladman, S. L., Seemann, T., Bulach, D. M., Chandry, P. S., Cross, K. J., Cleal, S. M., & Reynolds, E. C. (2017). Porphyromonas gingivalisUses Specific Domain Rearrangements and Allelic Exchange to Generate Diversity in Surface Virulence Factors. Frontiers in microbiology, 8, 48. https://doi.org/10.3389/fmicb.2017.00048 Delgado-Angulo, E. K., Bernabé, E., & Marcenes, W. (2016). Ethnic inequalities in periodontal disease among British adults. Journal of clinical periodontology, 43(11), 926–933. https://doi.org/10.1111/jcpe.12605 Delgado-Vega, A. M., Martín, J., Granados, J., & Anaya, J. M. (2006). Epidemiología genética de la artritis reumatoide: qué esperar de América Latina? Biomedica: revista del Instituto Nacional de Salud, 26(4), 562–584 de Pablo, P., Dietrich, T., & McAlindon, T. E. (2008). Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. The Journal of rheumatology, 35(1), 70–76. de Smit, M., van de Stadt, L. A., Janssen, K. M., Doornbos-van der Meer, B., Vissink, A., van Winkelhoff, A. J., Brouwer, E., Westra, J., & van Schaardenburg, D. (2014). Antibodies against Porphyromonas gingivalis in seropositive arthralgia patients do not predict development of rheumatoid arthritis. Annals of the rheumatic diseases, 73(6), 1277–1279. https://doi.org/10.1136/annrheumdis-2013-204594 de Vries, C., Ruacho, G., Kindstedt, E., Potempa, B. A., Potempa, J., Klinge, B., Lundberg, P., Svenungsson, E., & Lundberg, K. (2022). Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction. Journal of clinical medicine, 11(4), 1008. https://doi.org/10.3390/jcm11041008 Derksen, V., Huizinga, T., & van der Woude, D. (2017). The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Seminars in immunopathology, 39(4), 437–446. https://doi.org/10.1007/s00281-017-0627-z Dominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., Holsinger, L. J., Arastu-Kapur, S., Kaba, S., Lee, A., Ryder, M. I., Potempa, B., Mydel, P., Hellvard, A., Adamowicz, K., Hasturk, H., … Potempa, J. (2019). Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances, 5(1), eaau3333. https://doi.org/10.1126/sciadv.aau3333 Eke, P. I., Page, R. C., Wei, L., Thornton-Evans, G., & Genco, R. J. (2012). Update of the case definitions for population-based surveillance of periodontitis. Journal of periodontology, 83(12), 1449–1454. https://doi.org/10.1902/jop.2012.110664 Eke, P. I., Wei, L., Borgnakke, W. S., Thornton-Evans, G., Zhang, X., Lu, H., McGuire, L. C., & Genco, R. J. (2016). Periodontitis prevalence in adults ≥ 65 years of age, in the USA. Periodontology 2000, 72(1), 76–95. https://doi.org/10.1111/prd.12145 Eke, P. I., Thornton-Evans, G. O., Wei, L., Borgnakke, W. S., Dye, B. A., & Genco, R. J. (2018). Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009-2014. Journal of the American Dental Association (1939), 149(7), 576–588.e6. https://doi.org/10.1016/j.adaj.2018.04.023 Eriksson, K., Fei, G., Lundmark, A., Benchimol, D., Lee, L., Hu, Y., Kats, A., Saevarsdottir, S., Catrina, A. I., Klinge, B., Andersson, A. F., Klareskog, L., Lundberg, K., Jansson, L., & Yucel-Lindberg, T. (2019). Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis. Journal of clinical medicine, 8(5), 630. https://doi.org/10.3390/jcm8050630 Federici, M. M., Venkat, K., Bam, N., Patel, K., Dal Monte, P. R., Fernie, B., Hensley, P., Carr, S., Baldoni, J., Truneh, A., & Erickson, J. (2003). Detection and consequences of recombinant protein isoforms: implications for biological potency. Developments in biologicals, 113, 53–114. Firestein, G. S., Budd, R., Gabriel, S. E., O’Dell, J. R., & McInnes, I. B. Kelley’s Textbook of Rheumatology: Expert Consult Premium Edition. Elsevier Health Sciences; 9th Ed. Páginas 1059-1074; 2013. ISBN 978-1-4377-1738-9. Firestein, G. S., & McInnes, I. B. (2017). Immunopathogenesis of Rheumatoid Arthritis. Immunity, 46(2), 183–196. https://doi.org/10.1016/j.immuni.2017.02.006 Fisher, B. A., Cartwright, A. J., Quirke, A. M., de Pablo, P., Romaguera, D., Panico, S., Mattiello, A., Gavrila, D., Navarro, C., Sacerdote, C., Vineis, P., Tumino, R., Lappin, D. F., Apatzidou, D., Culshaw, S., Potempa, J., Michaud, D. S., Riboli, E., & Venables, P. J. (2015). Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. BMC musculoskeletal disorders, 16, 331. https://doi.org/10.1186/s12891-015-0792-y Fitzpatrick, R. E., Wijeyewickrema, L. C., & Pike, R. N. (2009). The gingipains: scissors and glue of the periodontal pathogen, Porphyromonas gingivalis. Future microbiology, 4(4), 471–487. https://doi.org/10.2217/fmb.09.18 Fransen J., Stucki G., van Riel PLCM. (2003). Rheumatoid arthritis measures: Disease Activity Score (DAS), Disease Activity Score-28 (DAS28), Rapid Assessment of Disease Activity in Rheumatology (RADAR), and Rheumatoid Arthritis Disease Activity Index (RADAI). Arthritis Rheum, 49 (5S), S214–224. https://doi.org/:10.1002/art.11407 Gabriel S. E. (2001). The epidemiology of rheumatoid arthritis. Rheumatic diseases clinics of North America, 27(2), 269–281. https://doi.org/10.1016/s0889-857x(05)70201-5 Gabarrini, G., Chlebowicz, M. A., Vega Quiroz, M. E., Veloo, A., Rossen, J., Harmsen, H., Laine, M. L., van Dijl, J. M., & van Winkelhoff, A. J. (2018). Conserved Citrullinating Exoenzymes in Porphyromonas Species. Journal of dental research, 97(5), 556–562. https://doi.org/10.1177/0022034517747575 García, J., Santana, Z., Zumalacárregui, L., Quintana, M., González, D., Furrazola, G., Cruz, O. (2013). Estrategias de obtención de proteínas recombinantes en Escherichia coli. VacciMonitor, 22(2):30-39. Gawron, K., Bereta, G., Nowakowska, Z., Lazarz-Bartyzel, K., Lazarz, M., Szmigielski, B., Mizgalska, D., Buda, A., Koziel, J., Oruba, Z., Chomyszyn-Gajewska, M., & Potempa, J. (2014). Peptidylarginine deiminase from Porphyromonas gingivalis contributes to infection of gingival fibroblasts and induction of prostaglandin E2 -signaling pathway. Molecular oral microbiology, 29(6), 321–332. https://doi.org/10.1111/omi.12081 Ghayoumi, N., Chen, C., & Slots, J. (2002). Dialister pneumosintes, a new putative periodontal pathogen. Journal of periodontal research, 37(1), 75–78. https://doi.org/10.1034/j.1600-0765.2002.05019.x Giles, J. T., Fert-Bober, J., Park, J. K., Bingham, C. O., 3rd, Andrade, F., Fox-Talbot, K., Pappas, D., Rosen, A., van Eyk, J., Bathon, J. M., & Halushka, M. K. (2012). Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study. Arthritis research & therapy, 14(1), R39. https://doi.org/10.1186/ar3752 Gómez-Bañuelos, E., Mukherjee, A., Darrah, E., & Andrade, F. (2019). Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Journal of clinical medicine, 8(9), 1309. https://doi.org/10.3390/jcm8091309 Gorasia, D. G., Lunar Silva, I., Butler, C. A., Chabalier, M., Doan, T., Cascales, E., Veith, P. D., & Reynolds, E. C. (2022). Protein Interactome Analysis of the Type IX Secretion System Identifies PorW as the Missing Link between the PorK/N Ring Complex and the Sov Translocon. Microbiology spectrum, 10(1), e0160221. https://doi.org/10.1128/spectrum.01602-21 Gorasia, D. G., Veith, P. D., Chen, D., Seers, C. A., Mitchell, H. A., Chen, Y. Y., Glew, M. D., Dashper, S. G., & Reynolds, E. C. (2015). Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism. PLoS pathogens, 11(9), e1005152. https://doi.org/10.1371/journal.ppat.1005152 Goulas, T., Mizgalska, D., Garcia-Ferrer, I., Kantyka, T., Guevara, T., Szmigielski, B., Sroka, A., Millán, C., Usón, I., Veillard, F., Potempa, B., Mydel, P., Solà, M., Potempa, J., & Gomis-Rüth, F. X. (2015). Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. Scientific reports, 5, 11969. https://doi.org/10.1038/srep11969 Graves D. (2008). Cytokines that promote periodontal tissue destruction. Journal of periodontology, 79(8 Suppl), 1585–1591. https://doi.org/10.1902/jop.2008.080183 Guevara, T., Rodríguez-Banqueri, A., Lasica, A. M., Ksiazek, M., Potempa, B. A., Potempa, J., & Gomis-Rüth, F. X. (2019). Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor. Scientific reports, 9(1), 4935. https://doi.org/10.1038/s41598-019-41354-3 Gully, N., Bright, R., Marino, V., Marchant, C., Cantley, M., Haynes, D., Butler, C., Dashper, S., Reynolds, E., & Bartold, M. (2014). Porphyromonas gingivalis peptidylarginine deiminase, a key contributor in the pathogenesis of experimental periodontal disease and experimental arthritis. PloS one, 9(6), e100838. https://doi.org/10.1371/journal.pone.0100838 Hajishengallis G. (2015). Periodontitis: from microbial immune subversion to systemic inflammation. Nature reviews. Immunology, 15(1), 30–44. https://doi.org/10.1038/nri3785 Hajishengallis, G., Darveau, R. P., & Curtis, M. A. (2012). The keystone-pathogen hypothesis. Nature reviews. Microbiology, 10(10), 717–725. https://doi.org/10.1038/nrmicro2873 Hamamoto, Y., Ouhara, K., Munenaga, S., Shoji, M., Ozawa, T., Hisatsune, J., Kado, I., Kajiya, M., Matsuda, S., Kawai, T., Mizuno, N., Fujita, T., Hirata, S., Tanimoto, K., Nakayama, K., Kishi, H., Sugiyama, E., & Kurihara, H. (2020). Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model. Arthritis research & therapy, 22(1), 249. https://doi.org/10.1186/s13075-020-02348-z Hedström, A. K., Stawiarz, L., Klareskog, L., & Alfredsson, L. (2018). Smoking and susceptibility to rheumatoid arthritis in a Swedish population-based case-control study. European journal of epidemiology, 33(4), 415–423. https://doi.org/10.1007/s10654-018-0360-5 Heredia-P, A. M., Lafaurie, G. I., Bautista-Molano, W., Trujillo, T. G., Chalem-Choueka, P., Bello-Gualtero, J. M., Pacheco-Tena, C., Chila-Moreno, L., & Romero-Sánchez, C. (2019). Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: a cohort study. BMC oral health, 19(1), 240. https://doi.org/10.1186/s12903-019-0939-6 Hirai, K., Yamaguchi-Tomikawa, T., Eguchi, T., Maeda, H., & Takashiba, S. (2020). Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis. Frontiers in immunology, 11, 1017. https://doi.org/10.3389/fimmu.2020.01017 Hitchon, C. A., Chandad, F., Ferucci, E. D., Willemze, A., Ioan-Facsinay, A., van der Woude, D., Markland, J., Robinson, D., Elias, B., Newkirk, M., Toes, R. M., Huizinga, T. W., & El-Gabalawy, H. S. (2010). Antibodies to Porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. The Journal of rheumatology, 37(6), 1105–1112. https://doi.org/10.3899/jrheum.091323 Huck, O., You, J., Han, X., Cai, B., Panek, J., & Amar, S. (2018). Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model. Infection and immunity, 86(9), e00356-18. https://doi.org/10.1128/IAI.00356-18 Imamura T. (2003)a. The role of gingipains in the pathogenesis of periodontal disease. Journal of periodontology, 74(1), 111–118. https://doi.org/10.1902/jop.2003.74.1.111 Imamura, T., Travis, J., & Potempa, J. (2003)b. The biphasic virulence activities of gingipains: activation and inactivation of host proteins. Current protein & peptide science, 4(6), 443–450. https://doi.org/10.2174/1389203033487027 Ingalagi, P., Bhat, K. G., Kulkarni, R. D., Kotrashetti, V. S., Kumbar, V., & Kugaji, M. (2022). Detection and comparison of prevalence of Porphyromonas gingivalis through culture and Real Time-polymerase chain reaction in subgingival plaque samples of chronic periodontitis and healthy individuals. Journal of oral and maxillofacial pathology: JOMFP, 26(2), 288. https://doi.org/10.4103/jomfp.jomfp_163_21 Jang, S., Kwon, E. J., & Lee, J. J. (2022). Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells. International journal of molecular sciences, 23(2), 905. https://doi.org/10.3390/ijms23020905 Jasemi, S., Erre, G. L., Cadoni, M. L., Bo, M., & Sechi, L. A. (2021). Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients. Journal of clinical medicine, 10(21), 5153. https://doi.org/10.3390/jcm10215153 Jenning, M., Marklein, B., Ytterberg, J., Zubarev, R. A., Joshua, V., van Schaardenburg, D., van de Stadt, L., Catrina, A. I., Nonhoff, U., Häupl, T., Konthur, Z., Burmester, G. R., & Skriner, K. (2020). Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Annals of the rheumatic diseases, 79(9), 1194–1202. https://doi.org/10.1136/annrheumdis-2019-216919 Jeong, H., Kim, H. J., & Lee, S. J. (2015). Complete Genome Sequence of Escherichia coli Strain BL21. Genome announcements, 3(2), e00134-15. https://doi.org/10.1128/genomeA.00134-15 Jia, L., Han, N., Du, J., Guo, L., Luo, Z., & Liu, Y. (2019). Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors. Frontiers in cellular and infection microbiology, 9, 262. https://doi.org/10.3389/fcimb.2019.00262 Johansson, L., Sherina, N., Kharlamova, N., Potempa, B., Larsson, B., Israelsson, L., Potempa, J., Rantapää-Dahlqvist, S., & Lundberg, K. (2016). Concentration of antibodies against Porphyromonas gingivalis increased before the onset of symptoms of rheumatoid arthritis. Arthritis research & therapy, 18(1), 201. https://doi.org/10.1186/s13075-016-1100-4 Jung, H., Jung, S. M., Rim, Y. A., Park, N., Nam, Y., Lee, J., Park, S. H., & Ju, J. H. (2017). Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice. PloS one, 12(11), e0188698. https://doi.org/10.1371/journal.pone.0188698 Kadowaki, T., Yoneda, M., Okamoto, K., Maeda, K., & Yamamoto, K. (1994). Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis. The Journal of biological chemistry, 269(33), 21371–21378. Kharlamova, N., Jiang, X., Sherina, N., Potempa, B., Israelsson, L., Quirke, A. M., Eriksson, K., Yucel-Lindberg, T., Venables, P. J., Potempa, J., Alfredsson, L., & Lundberg, K. (2016). Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. Arthritis & rheumatology (Hoboken, N.J.), 68(3), 604–613. https://doi.org/10.1002/art.39491 Klareskog, L., Widhe, M., Hermansson, M., & Rönnelid, J. (2008). Antibodies to citrullinated proteins in arthritis: pathology and promise. Current opinion in rheumatology, 20(3), 300–305. https://doi.org/10.1097/BOR.0b013e3282fbd22a Konig, M. F., Paracha, A. S., Moni, M., Bingham, C. O., 3rd, & Andrade, F. (2015). Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology. Annals of the rheumatic diseases, 74(11), 2054–2061. https://doi.org/10.1136/annrheumdis-2014-205385 Kwon, T., Lamster, I. B., & Levin, L. (2021). Current Concepts in the Management of Periodontitis. International dental journal, 71(6), 462–476. https://doi.org/10.1111/idj.12630 Kuramitsu H. K. (1998). Proteases of Porphyromonas gingivalis: what don't they do?. Oral microbiology and immunology, 13(5), 263–270. https://doi.org/10.1111/j.1399-302x.1998.tb00706.x Krutyhołowa, A., Strzelec, K., Dziedzic, A., Bereta, G. P., Łazarz-Bartyzel, K., Potempa, J., & Gawron, K. (2022). Host and bacterial factors linking periodontitis and rheumatoid arthritis. Frontiers in immunology, 13, 980805. https://doi.org/10.3389/fimmu.2022.980805 Lafaurie, G. I., Neuta, Y., Ríos, R., Pacheco-Montealegre, M., Pianeta, R., Castillo, D. M., Herrera, D., Reyes, J., Diaz, L., Castillo, Y., Sanz, M., & Iniesta, M. (2022). Differences in the subgingival microbiome according to stage of periodontitis: A comparison of two geographic regions. PloS one, 17(8), e0273523. https://doi.org/10.1371/journal.pone.0273523 Lafaurie, G.I., Castillo, D.M., Iniesta, M., Sanz, M., Gómez, L. A., Castillo, Y., Pianeta, R., Delgadillo, N.A., Neuta, Y., Diaz-Báez, D., Herrera, D. (2023). Differential analysis of culturable and unculturable subgingival target microorganisms according to the stages of periodontitis. Clinical Oral Investigations (Aceptado para publicación). Lafaurie, G. I., Mayorga-Fayad, I., Torres, M. F., Castillo, D. M., Aya, M. R., Barón, A., & Hurtado, P. A. (2007a). Periodontopathic microorganisms in peripheric blood after scaling and root planing. Journal of clinical periodontology, 34(10), 873–879. https://doi.org/10.1111/j.1600-051X.2007.01125.x Lafaurie, G. I., Contreras, A., Barón, A., Botero, J., Mayorga-Fayad, I., Jaramillo, A., Giraldo, A., González, F., Mantilla, S., Botero, A., Archila, L. H., Díaz, A., Chacón, T., Castillo, D. M., Betancourt, M., Del Rosario Aya, M., & Arce, R. (2007b). Demographic, clinical, and microbial aspects of chronic and aggressive periodontitis in Colombia: a multicenter study. Journal of periodontology, 78(4), 629–639. https://doi.org/10.1902/jop.2007.060187 Laugisch, O., Wong, A., Sroka, A., Kantyka, T., Koziel, J., Neuhaus, K., Sculean, A., Venables, P. J., Potempa, J., Möller, B., & Eick, S. (2016). Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis. Clinical oral investigations, 20(4), 675–683. https://doi.org/10.1007/s00784-015-1556-7 Lee, J. Y., Choi, I. A., Kim, J. H., Kim, K. H., Lee, E. Y., Lee, E. B., Lee, Y. M., & Song, Y. W. (2015). Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA. BMC musculoskeletal disorders, 16, 190. https://doi.org/10.1186/s12891-015-0647-6 Leech, M. T., & Bartold, P. M. (2015). The association between rheumatoid arthritis and periodontitis. Best practice & research. Clinical rheumatology, 29(2), 189–201. https://doi.org/10.1016/j.berh.2015.03.001 Li, Y., Guo, R., Oduro, P. K., Sun, T., Chen, H., Yi, Y., Zeng, W., Wang, Q., Leng, L., Yang, L., & Zhang, J. (2022). The Relationship Between Porphyromonas gingivalis and Rheumatoid Arthritis: A Meta-Analysis. Frontiers in cellular and infection microbiology, 12, 956417. https://doi.org/10.3389/fcimb.2022.956417 Li, N., & Collyer, C. A. (2011). Gingipains from Porphyromonas gingivalis- Complex domain structures confer diverse functions. European journal of microbiology & immunology, 1(1), 41–58. https://doi.org/10.1556/EuJMI.1.2011.1.7 Liu, X., Zou, Q., Zeng, B., Fang, Y., & Wei, H. (2013). Analysis of fecal Lactobacillus community structure in patients with early rheumatoid arthritis. Current microbiology, 67(2), 170–176. https://doi.org/10.1007/s00284-013-0338-1 Loutan, L., Alpizar-Rodriguez, D., Courvoisier, D. S., Finckh, A., Mombelli, A., & Giannopoulou, C. (2019). Periodontal status correlates with anti-citrullinated protein antibodies in first-degree relatives of individuals with rheumatoid arthritis. Journal of clinical periodontology, 46(7), 690–698. https://doi.org/10.1111/jcpe.13117 Lübcke, P. M., Ebbers, M., Volzke, J., Bull, J., Kneitz, S., Engelmann, R., Lang, H., Kreikemeyer, B., & Müller-Hilke, B. (2019). Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss. Scientific reports, 9(1), 8128. https://doi.org/10.1038/s41598-019-44512-9 Ma, K. S., Chiang, C. H., Chen, Y. W., & Wang, L. T. (2021). Correspondence to 'Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production'. Annals of the rheumatic diseases, annrheumdis-2020-219255. Advance online publication. https://doi.org/10.1136/annrheumdis-2020-219255 Mangat, P., Wegner, N., Venables, P. J., & Potempa, J. (2010). Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?. Arthritis research & therapy, 12(3), 209. https://doi.org/10.1186/ar3000 Margetts, M. B., Barr, I. G., & Webb, E. A. (2000). Overexpression, purification, and refolding of a Porphyromonas gingivalis cysteine protease from Escherichia coli. Protein expression and purification, 18(3), 262–268. https://doi.org/10.1006/prep.2000.1193 Mantri, C. K., Chen, C. H., Dong, X., Goodwin, J. S., Pratap, S., Paromov, V., & Xie, H. (2015). Fimbriae-mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis. MicrobiologyOpen, 4(1), 53–65. https://doi.org/10.1002/mbo3.221 Marchesan, J. T., Gerow, E. A., Schaff, R., Taut, A. D., Shin, S. Y., Sugai, J., Brand, D., Burberry, A., Jorns, J., Lundy, S. K., Nuñez, G., Fox, D. A., & Giannobile, W. V. (2013). Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis. Arthritis research & therapy, 15(6), R186. https://doi.org/10.1186/ar4376 Maresz, K. J., Hellvard, A., Sroka, A., Adamowicz, K., Bielecka, E., Koziel, J., Gawron, K., Mizgalska, D., Marcinska, K. A., Benedyk, M., Pyrc, K., Quirke, A. M., Jonsson, R., Alzabin, S., Venables, P. J., Nguyen, K. A., Mydel, P., & Potempa, J. (2013). Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD). PLoS pathogens, 9(9), e1003627. https://doi.org/10.1371/journal.ppat.1003627 Martínez-Rivera, J. I., Xibillé-Friedmann, D. X., González-Christen, J., de la Garza-Ramos, M. A., Carrillo-Vázquez, S. M., & Montiel-Hernández, J. L. (2017). Salivary ammonia levels and Tannerella forsythia are associated with rheumatoid arthritis: A cross sectional study. Clinical and experimental dental research, 3(3), 107–114. https://doi.org/10.1002/cre2.68 Mayorga-Fayad, I., Lafaurie, G. I., Contreras, A., Castillo, D. M., Barón, A., & Aya, M. (2007). Microflora subgingival en periodontitis crónica y agresiva en Bogotá, Colombia: un acercamiento epidemiológico. Biomedica : revista del Instituto Nacional de Salud, 27(1), 21–33. McGraw, W. T., Potempa, J., Farley, D., & Travis, J. (1999). Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infection and immunity, 67(7), 3248–3256. https://doi.org/10.1128/IAI.67.7.3248-3256.1999 Ministerio de salud. Estudio Nacional En Salud Bucal (ENSAB IV). Bogotá, Colombia. 2014;4.Consultado en: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENSAB-IV-Situacion-Bucal-Actual.pdf Mikuls, T. R., Payne, J. B., Yu, F., Thiele, G. M., Reynolds, R. J., Cannon, G. W., Markt, J., McGowan, D., Kerr, G. S., Redman, R. S., Reimold, A., Griffiths, G., Beatty, M., Gonzalez, S. M., Bergman, D. A., Hamilton, B. C., 3rd, Erickson, A. R., Sokolove, J., Robinson, W. H., Walker, C., … O'Dell, J. R. (2014). Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N.J.), 66(5), 1090–1100. https://doi.org/10.1002/art.38348 Montgomery, A. B., Kopec, J., Shrestha, L., Thezenas, M. L., Burgess-Brown, N. A., Fischer, R., Yue, W. W., & Venables, P. J. (2016). Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis. Annals of the rheumatic diseases, 75(6), 1255–1261. https://doi.org/10.1136/annrheumdis-2015-207656 Moen, K., Brun, J. G., Madland, T. M., Tynning, T., & Jonsson, R. (2003). Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients. Clinical and diagnostic laboratory immunology, 10(6), 1043–1050. https://doi.org/10.1128/cdli.10.6.1043-1050.2003 Morales, L., Velandia, M. L., Calderon, M. A., Castellanos, J. E., & Chaparro-Olaya, J. (2017). Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue. Biomedica: revista del Instituto Nacional de Salud, 37(1), 131–140. https://doi.org/10.7705/biomedica.v37i1.3249 Moses, T., & Holland, P. W. (2010). A comparison of statistical selection strategies for univariate and bivariate log-linear models. The British journal of mathematical and statistical psychology, 63(Pt 3), 557–574. https://doi.org/10.1348/000711009X478580 Muñoz-Atienza, E., Flak, M. B., Sirr, J., Paramonov, N. A., Aduse-Opoku, J., Pitzalis, C., & Curtis, M. A. (2020). The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis. Journal of dental research, 99(4), 456–462. https://doi.org/10.1177/0022034519898144 Munenaga, S., Ouhara, K., Hamamoto, Y., Kajiya, M., Takeda, K., Yamasaki, S., Kawai, T., Mizuno, N., Fujita, T., Sugiyama, E., & Kurihara, H. (2018). The involvement of C5a in the progression of experimental arthritis with Porphyromonas gingivalis infection in SKG mice. Arthritis research & therapy, 20(1), 247. https://doi.org/10.1186/s13075-018-1744-3 Nakao, R., Takashiba, S., Kosono, S., Yoshida, M., Watanabe, H., Ohnishi, M., & Senpuku, H. (2014). Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses. Microbes and infection, 16(1), 6–16. https://doi.org/10.1016/j.micinf.2013.10.005 Nakayama, K., Kadowaki, T., Okamoto, K., & Yamamoto, K. (1995). Construction and characterization of arginine-specific cysteine proteinase (Arg-gingipain)-deficient mutants of Porphyromonas gingivalis. Evidence for significant contribution of Arg-gingipain to virulence. The Journal of biological chemistry, 270(40), 23619–23626. https://doi.org/10.1074/jbc.270.40.23619 Nemoto, T. K., & Ohara-Nemoto, Y. (2016). Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism. The Japanese dental science review, 52(1), 22–29. https://doi.org/10.1016/j.jdsr.2015.08.002 Nunes, J. M., Fillis, T., Page, M. J., Venter, C., Lancry, O., Kell, D. B., Windberger, U., & Pretorius, E. (2020). Gingipain R1 and Lipopolysaccharide From Porphyromonas gingivalis Have Major Effects on Blood Clot Morphology and Mechanics. Frontiers in immunology, 11, 1551. https://doi.org/10.3389/fimmu.2020.01551 Okada, M., Kobayashi, T., Ito, S., Yokoyama, T., Abe, A., Murasawa, A., & Yoshie, H. (2013). Periodontal treatment decreases levels of antibodies to Porphyromonas gingivalis and citrulline in patients with rheumatoid arthritis and periodontitis. Journal of periodontology, 84(12), e74–e84. https://doi.org/10.1902/jop.2013.130079 Okada, M., Kobayashi, T., Ito, S., Yokoyama, T., Komatsu, Y., Abe, A., Murasawa, A., & Yoshie, H. (2011). Antibody responses to periodontopathic bacteria in relation to rheumatoid arthritis in Japanese adults. Journal of periodontology, 82(10), 1433–1441. https://doi.org/10.1902/jop.2011.110020 Olsen, I., Singhrao, S. K., & Potempa, J. (2018). Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer's disease. Journal of oral microbiology, 10(1), 1487742. https://doi.org/10.1080/20002297.2018.1487742 Owczarek, B., Gerszberg, A., & Hnatuszko-Konka, K. (2019). A Brief Reminder of Systems of Production and Chromatography-Based Recovery of Recombinant Protein Biopharmaceuticals. BioMed research international, 2019, 4216060. https://doi.org/10.1155/2019/4216060 Padyukov L. (2022). Genetics of rheumatoid arthritis. Seminars in immunopathology, 44(1), 47–62. https://doi.org/10.1007/s00281-022-00912-0 Page, R. C., & Eke, P. I. (2007). Case definitions for use in population-based surveillance of periodontitis. Journal of periodontology, 78(7 Suppl), 1387–1399. https://doi.org/10.1902/jop.2007.060264 Pathirana, R. D., O'Brien-Simpson, N. M., Veith, P. D., Riley, P. F., & Reynolds, E. C. (2006). Characterization of proteinase-adhesin complexes of Porphyromonas gingivalis. Microbiology (Reading, England), 152(Pt 8), 2381–2394. https://doi.org/10.1099/mic.0.28787-0 Pathirana, R. D., O'Brien-Simpson, N. M., Brammar, G. C., Slakeski, N., & Reynolds, E. C. (2007). Kgp and RgpB, but not RgpA, are important for Porphyromonas gingivalis virulence in the murine periodontitis model. Infection and immunity, 75(3), 1436–1442. https://doi.org/10.1128/IAI.01627-06 Pianta, A., Arvikar, S., Strle, K., Drouin, E. E., Wang, Q., Costello, C. E., & Steere, A. C. (2017). Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.), 69(5), 964–975. https://doi.org/10.1002/art.40003 Posada-López, A., Botero, J. E., Pineda-Tamayo, R. A., & Agudelo-Suárez, A. A. (2022). The Effect of Periodontal Treatment on Clinical and Biological Indicators, Quality of Life, and Oral Health in Rheumatoid Arthritis Patients: A Quasi-Experimental Study. International journal of environmental research and public health, 19(3), 1789. https://doi.org/10.3390/ijerph19031789 Potempa, J., Mydel, P., & Koziel, J. (2017). The case for periodontitis in the pathogenesis of rheumatoid arthritis. Nature reviews. Rheumatology, 13(10), 606–620. https://doi.org/10.1038/nrrheum.2017.132 Potempa J, Nguyen KA (2007). Purification and characterization of gingipains. Curr Protoc Protein Sci. Chapter 21. Potempa, J., Sroka, A., Imamura, T., & Travis, J. (2003). Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes. Current protein & peptide science, 4(6), 397–407. https://doi.org/10.2174/1389203033487036 Potempa, J., Pavloff, N., & Travis, J. (1995)a. Porphyromonas gingivalis: a proteinase/gene accounting audit. Trends in microbiology, 3(11), 430–434. https://doi.org/10.1016/s0966-842x(00)88996-9 Potempa, J., Pike, R., & Travis, J. (1995)b. The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain. Infection and immunity, 63(4), 1176–1182. https://doi.org/10.1128/iai.63.4.1176-1182.1995 Puszczewicz, M., & Iwaszkiewicz, C. (2011). Role of anti-citrullinated protein antibodies in diagnosis and prognosis of rheumatoid arthritis. Archives of medical science: AMS, 7(2), 189–194. https://doi.org/10.5114/aoms.2011.22067 Qiao, Y., Wang, Z., Li, Y., Han, Y., Zhou, Y., & Cao, X. (2020). Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis. Joint bone spine, 87(6), 556–564. https://doi.org/10.1016/j.jbspin.2020.04.024 Qin, B., Yang, M., Fu, H., Ma, N., Wei, T., Tang, Q., Hu, Z., Liang, Y., Yang, Z., & Zhong, R. (2015). Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis research & therapy, 17(1), 86. https://doi.org/10.1186/s13075-015-0601-x Quirke, A. M., Lugli, E. B., Wegner, N., Hamilton, B. C., Charles, P., Chowdhury, M., Ytterberg, A. J., Zubarev, R. A., Potempa, J., Culshaw, S., Guo, Y., Fisher, B. A., Thiele, G., Mikuls, T. R., & Venables, P. J. (2014). Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis. Annals of the rheumatic diseases, 73(1), 263–269. https://doi.org/10.1136/annrheumdis-2012-202726 Rahajoe, P. S., de Smit, M., Schuurmans, G., Raveling-Eelsing, E., Kertia, N., Vissink, A., & Westra, J. (2020). Increased IgA anti-citrullinated protein antibodies in the periodontal inflammatory exudate of healthy individuals compared to rheumatoid arthritis patients. Journal of clinical periodontology, 47(5), 552–560. https://doi.org/10.1111/jcpe.13277 Repeke, C. E., Cardoso, C. R., Claudino, M., Silveira, E. M., Trombone, A. P., Campanelli, A. P., Silva, J. S., Martins, W., Jr, & Garlet, G. P. (2012). Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation. Journal of applied oral science : revista FOB, 20(1), 113–121. https://doi.org/10.1590/s1678-77572012000100020 Richards D. (2014). Review finds that severe periodontitis affects 11% of the world population. Evidence-based dentistry, 15(3), 70–71. https://doi.org/10.1038/sj.ebd.6401037 Rodríguez, J., Lafaurie, G. I., Bautista-Molano, W., Chila-Moreno, L., Bello-Gualtero, J. M., & Romero-Sánchez, C. (2021). Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study. Clinical oral investigations, 25(4), 1685–1695. https://doi.org/10.1007/s00784-020-03469-0 Rodríguez, S. B., Stitt, B. L., & Ash, D. E. (2009). Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization. Archives of biochemistry and biophysics, 488(1), 14–22. https://doi.org/10.1016/j.abb.2009.06.010 Röhner, E., Detert, J., Kolar, P., Hocke, A., N'Guessan, P., Matziolis, G., Kanitz, V., Bernimoulin, J. P., Kielbassa, A., Burmester, G. R., Buttgereit, F., & Pischon, N. (2010). Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis. Calcified tissue international, 87(4), 333–340. https://doi.org/10.1007/s00223-010-9389-5 Romero-Sánchez, C., Rodríguez, C., Santos-Moreno, P., Mesa, A. M., Lafaurie, G. I., Giraldo-Q, S., De-Avila, J., Castillo, D. M., Duran, M., Chalem, P. C., Bello Gualtero, J. M., & Valle-Oñate, R. (2017). Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?. Current rheumatology reviews, 13(2), 139–151. https://doi.org/10.2174/1573397113666170407161520 Rovas, A., Puriene, A., Punceviciene, E., Butrimiene, I., Stuopelyte, K., & Jarmalaite, S. (2021). Associations of periodontal status in periodontitis and rheumatoid arthritis patients. Journal of periodontal & implant science, 51(2), 124–134. https://doi.org/10.5051/jpis.2006060303 Sato, K., Takahashi, N., Kato, T., Matsuda, Y., Yokoji, M., Yamada, M., Nakajima, T., Kondo, N., Endo, N., Yamamoto, R., Noiri, Y., Ohno, H., & Yamazaki, K. (2017). Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Scientific reports, 7(1), 6955. https://doi.org/10.1038/s41598-017-07196-7 Schenkein, H. A., Bradley, J. L., & Purkall, D. B. (2013). Anticardiolipin in Porphyromonas gingivalis antisera causes fetal loss in mice. Journal of dental research, 92(9), 814–818. https://doi.org/10.1177/0022034513497959 Schmalz, G., Noack, S., Patschan, S., Patschan, D., Müller, G. A., Rupprecht, A., Schmickler, J., Haak, R., & Ziebolz, D. (2020). Disease activity, morning stiffness and missing teeth are associated with oral health-related quality of life in individuals with rheumatoid arthritis. Clinical oral investigations, 24(10), 3559–3566. https://doi.org/10.1007/s00784-020-03226-3 Schmickler, J., Rupprecht, A., Patschan, S., Patschan, D., Müller, G. A., Haak, R., Mausberg, R. F., Schmalz, G., Kottmann, T., & Ziebolz, D. (2017). Cross-Sectional Evaluation of Periodontal Status and Microbiologic and Rheumatoid Parameters in a Large Cohort of Patients With Rheumatoid Arthritis. Journal of periodontology, 88(4), 368–379. https://doi.org/10.1902/jop.2016.160355 Seers, C. A., Mahmud, A., Huq, N. L., Cross, K. J., & Reynolds, E. C. (2020). Porphyromonas gingivalis laboratory strains and clinical isolates exhibit different distribution of cell surface and secreted gingipains. Journal of oral microbiology, 13(1), 1858001. https://doi.org/10.1080/20002297.2020.1858001 Serrano, C., & Suarez, E. (2019). Prevalence of Severe Periodontitis in a Colombian Adult Population. Journal of the International Academy of Periodontology, 21(2), 53–62. Shimada, A., Kobayashi, T., Ito, S., Okada, M., Murasawa, A., Nakazono, K., & Yoshie, H. (2016). Expression of anti-Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase-4 in patients with rheumatoid arthritis and periodontitis. Journal of periodontal research, 51(1), 103–111. https://doi.org/10.1111/jre.12288 Sippert, E. Â., de Oliveira e Silva, C., Ayo, C. M., Marques, S. B., Visentainer, J. E., & Sell, A. M. (2015). HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients. Mediators of inflammation, 2015, 481656. https://doi.org/10.1155/2015/481656 Slots J. (1987). Detection of colonies of Bacteroides gingivalis by a rapid fluorescence assay for trypsin-like activity. Oral microbiology and immunology, 2(3), 139–141. https://doi.org/10.1111/j.1399-302x.1987.tb00279.x Slots, J., Bragd, L., Wikström, M., & Dahlén, G. (1986). The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. Journal of clinical periodontology, 13(6), 570–577. https://doi.org/10.1111/j.1600-051x.1986.tb00849.x Smalley, J. W., & Olczak, T. (2017). Heme acquisition mechanisms of Porphyromonas gingivalis strategies used in a polymicrobial community in a heme-limited host environment. Molecular oral microbiology, 32(1), 1–23. https://doi.org/10.1111/omi.12149 Smolen, J. S., Aletaha, D., & McInnes, I. B. (2016). Rheumatoid arthritis. Lancet (London, England), 388(10055), 2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8 Stobernack, T., Glasner, C., Junker, S., Gabarrini, G., de Smit, M., de Jong, A., Otto, A., Becher, D., van Winkelhoff, A. J., & van Dijl, J. M. (2016). Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis. Journal of proteome research, 15(12), 4532–4543. https://doi.org/10.1021/acs.jproteome.6b00634 Structural Genomics Consortium, China Structural Genomics Consortium, Northeast Structural Genomics Consortium, Gräslund, S., Nordlund, P., Weigelt, J., Hallberg, B. M., Bray, J., Gileadi, O., Knapp, S., Oppermann, U., Arrowsmith, C., Hui, R., Ming, J., dhe-Paganon, S., Park, H. W., Savchenko, A., Yee, A., Edwards, A., Vincentelli, R., … Gunsalus, K. C. (2008). Protein production and purification. Nature methods, 5(2), 135–146. https://doi.org/10.1038/nmeth.f.202 Sun, J., Zheng, Y., Bian, X., Ge, H., Wang, J., & Zhang, Z. (2021). Non-surgical periodontal treatment improves rheumatoid arthritis disease activity: a meta-analysis. Clinical oral investigations, 25(8), 4975–4985. https://doi.org/10.1007/s00784-021-03807-w Thermofisher. (2020). One Shot™ TOP10 Chemically Competent E. coli. [online] Available at: https://www.thermofisher.com/order/catalog/product/C404003?SID=srch-srp-C404003#/C404003?SID=srch-srp-C404003 [Accessed 7 Mar. 2020]. Theilade, E., Wright, W. H., Jensen, S. B., & Löe, H. (1966). Experimental gingivitis in man. II. A longitudinal clinical and bacteriological investigation. Journal of periodontal research, 1, 1–13. https://doi.org/10.1111/j.1600-0765.1966.tb01842.x Unriza-Puin, S., Bautista-Molano, W., Lafaurie, G. I., Valle-Oñate, R., Chalem, P., Chila-Moreno, L., Bello-Gualtero, J. M., & Romero-Sánchez, C. (2017). Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives?. Clinical rheumatology, 36(4), 799–806. https://doi.org/10.1007/s10067-016-3519-z Uhlig, T., Hagen, K. B., & Kvien, T. K. (1999). Current tobacco smoking, formal education, and the risk of rheumatoid arthritis. The Journal of rheumatology, 26(1), 47–54. Usui, M., Onizuka, S., Sato, T., Kokabu, S., Ariyoshi, W., & Nakashima, K. (2021). Mechanism of alveolar bone destruction in periodontitis - Periodontal bacteria and inflammation. The Japanese dental science review, 57, 201–208. https://doi.org/10.1016/j.jdsr.2021.09.005 Veillard, F., Potempa, B., Guo, Y., Ksiazek, M., Sztukowska, M. N., Houston, J. A., Koneru, L., Nguyen, K. A., & Potempa, J. (2015). Purification and characterisation of recombinant His-tagged RgpB gingipain from Porphyromonas gingivalis. Biological chemistry, 396(4), 377–384. https://doi.org/10.1515/hsz-2014-0304 Vermilyea, D. M., Moradali, M. F., Kim, H. M., & Davey, M. E. (2021). PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis. Journal of bacteriology, 203(4), e00343-20. https://doi.org/10.1128/JB.00343-20 Vermilyea, D. M., Ottenberg, G. K., & Davey, M. E. (2019). Citrullination mediated by PPAD constrains biofilm formation in P. gingivalis strain 381. NPJ biofilms and microbiomes, 5(1), 7. https://doi.org/10.1038/s41522-019-0081-x Vidal, J., Canizález-Román, A., Gutiérrez-Jiménez, J., Navarro-García, F. (2007) Patogénesis molecular, epidemiología y diagnóstico de Escherichia coli enteropatógena. Salud Pública de México. 2007;49(5), 376-386. Vossenaar, E. R., Radstake, T. R., van der Heijden, A., van Mansum, M. A., Dieteren, C., de Rooij, D. J., Barrera, P., Zendman, A. J., & van Venrooij, W. J. (2004). Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Annals of the rheumatic diseases, 63(4), 373–381. https://doi.org/10.1136/ard.2003.012211 Wegner, N., Wait, R., Sroka, A., Eick, S., Nguyen, K. A., Lundberg, K., Kinloch, A., Culshaw, S., Potempa, J., & Venables, P. J. (2010). Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis and rheumatism, 62(9), 2662–2672. https://doi.org/10.1002/art.27552 Wilensky, A., Polak, D., Houri-Haddad, Y., & Shapira, L. (2013). The role of RgpA in the pathogenicity of Porphyromonas gingivalis in the murine periodontitis model. Journal of Clinical Periodontology, 40(10), 924–932. https://doi.org/10.1111/jcpe.12139 Wingrove, J. A., DiScipio, R. G., Chen, Z., Potempa, J., Travis, J., & Hugli, T. E. (1992). Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. The Journal of biological chemistry, 267(26), 18902–18907. Witalison, E. E., Thompson, P. R., & Hofseth, L. J. (2015). Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation. Current drug targets, 16(7), 700–710. https://doi.org/10.2174/1389450116666150202160954 Wirth, R., Pap, B., Maróti, G., Vályi, P., Komlósi, L., Barta, N., Strang, O., Minárovits, J., & Kovács, K. L. (2021). Toward Personalized Oral Diagnosis: Distinct Microbiome Clusters in Periodontitis Biofilms. Frontiers in cellular and infection microbiology, 11, 747814. https://doi.org/10.3389/fcimb.2021.747814 Xiao, L., Zhang, Q., Peng, Y., Wang, D., & Liu, Y. (2020). The effect of periodontal bacteria infection on incidence and prognosis of cancer: A systematic review and meta-analysis. Medicine, 99(15), e19698. https://doi.org/10.1097/MD.0000000000019698 Xie H. (2015). Biogenesis and function of Porphyromonas gingivalis outer membrane vesicles. Future microbiology, 10(9), 1517–1527. https://doi.org/10.2217/fmb.15.63 Xu, H., Zhao, H., Fan, D., Liu, M., Cao, J., Xia, Y., Ju, D., Xiao, C., & Guan, Q. (2020). Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis. Mediators of inflammation, 2020, 1430605. https://doi.org/10.1155/2020/1430605 Yamakawa, M., Ouhara, K., Kajiya, M., Munenaga, S., Kittaka, M., Yamasaki, S., Takeda, K., Takeshita, K., Mizuno, N., Fujita, T., Sugiyama, E., & Kurihara, H. (2016). Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice. Clinical and experimental immunology, 186(2), 177–189. https://doi.org/10.1111/cei.12847 Yuzhalin A. E. (2019). Citrullination in Cancer. Cancer research, 79(7), 1274–1284. https://doi.org/10.1158/0008-5472.CAN-18-2797 Zhou, N., Zou, F., Cheng, X., Huang, Y., Zou, H., Niu, Q., Qiu, Y., Shan, F., Luo, A., Teng, W., & Sun, J. (2021). Porphyromonas gingivalis induces periodontitis, causes immune imbalance, and promotes rheumatoid arthritis. Journal of leukocyte biology, 110(3), 461–473. https://doi.org/10.1002/JLB.3MA0121-045R Zhou, X. Y., Gao, J. L., Hunter, N., Potempa, J., & Nguyen, K. A. (2013). Sequence-independent processing site of the C-terminal domain (CTD) influences maturation of the RgpB protease from Porphyromonas gingivalis. Molecular microbiology, 89(5), 903–917. https://doi.org/10.1111/mmi.12319
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dc.rights.license.spa.fl_str_mv	Atribución-NoComercial-SinDerivadas 4.0 Internacional
dc.rights.uri.spa.fl_str_mv	http://creativecommons.org/licenses/by-nc-nd/4.0/
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dc.format.extent.spa.fl_str_mv	xxi, 96 páginas
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Bogotá - Ciencias - Doctorado en Biotecnología
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv	Bogotá, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Bogotá
institution	Universidad Nacional de Colombia
bitstream.url.fl_str_mv	https://repositorio.unal.edu.co/bitstream/unal/83320/2/52882038.2022.pdf https://repositorio.unal.edu.co/bitstream/unal/83320/1/license.txt
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spelling	Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Castellanos Parra, Jaime Eduardod005422b5147ff1af3f046ffaf4328e6Romero Sánchez, María Consueloadef63ccda8465428682bb4b85aab02bCastillo Perdomo, Diana Marcela290a242638aa37c84584c196fdce5fc0Unidad de Investigación Básica Oral - UIBOLafaurie Villamil Gloria InésCastillo, Diana Marcela [0000-0002-1846-7448]Castillo Perdomo, Diana Marcela [https://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000293580]Castillo, Diana Marcela [16300829800]Castillo, Diana Marcela [https://www.researchgate.net/profile/Diana-Castillo-4]Castillo, Diana Marcela [https://scholar.google.com/citations?user=_DyKomkAAAAJ&hl=es]2023-02-06T16:52:57Z2023-02-06T16:52:57Z2022-12-02https://repositorio.unal.edu.co/handle/unal/83320Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.coilustraciones, graficasEstudios clínicos y epidemiológicos han corroborado la asociación bidireccional entre la artritis reumatoide (AR) y la periodontitis. Esta asociación es atribuida a Porphyromonas gingivalis, por la presencia de la enzima peptidil arginina deiminasa (PPAD) y con la actividad de las Arg-gingipaínas en la citrulinación, vinculadas con el quiebre de la tolerancia inmunológica en la AR. Se ha confirmado que los anticuerpos anti-P. gingivalis acompañan el desarrollo de la AR. Sin embargo, pocos estudios indagan la asociación de factores de virulencia específicos de esta bacteria con la AR. En este estudio hemos producido la PPAD de manera recombinante y purificado la gingipaína RgpA nativa a partir de vesículas de membrana externa de P. gingivalis ATCC33277, la actividad enzimática se evaluó con sustratos fluorogénicos. La presencia de las proteínas se confirmó por SDS-PAGE y Western Blot y fueron usadas como antígenos en la detección de los anticuerpos contra estos factores de virulencia mediante ELISA en 143 pacientes con AR y 112 individuos sin AR. Se encontraron diferencias significativas en los títulos de anti-RgpA entre los dos grupos y se determinó asociación con el diagnóstico de AR (OR 4.09; IC 95% 1.2-13.9), mientras que los anti-PPAD no presentan diferencias. La interacción anti-RgpA/anti-PPAD se asoció con diagnósticos de AR (OR 6.63; IC 95% 1.61-27). Además, se purificaron con éxito los dos factores de virulencia de P. gingivalis y se desarrolló el ELISA, permitiendo la detección de los anticuerpos frente a estas proteínas. Los anticuerpos anti-RgpA y la doble positividad de los anticuerpos anti-RgpA/anti-PPAD pueden ser marcadores diagnósticos de la AR. (Texto tomado de la fuente)Clinical and epidemiological studies have confirmed the bidirectional association between rheumatoid arthritis (RA) and periodontitis. This association is attributed to Porphyromonas gingivalis, due to the presence of peptidyl arginine deiminase (PPAD) together with the action of Arg-gingipains in citrullination, linked to the alteration of immunological tolerance in RA. It has been confirmed that anti-P. gingivalis accompany the development of RA. Nevertheless. Few studies investigate the association of specific virulence factors of this bacterium with RA. In this study we have recombinantly produced PPAD and purified native RgpA gingipain from outer membrane vesicles of P. gingivalis ATCC33277, the enzymatic activity was evaluated with fluorogenic substrates. The presence of the proteins was confirmed by SDS-PAGE and Western Blot and they were used as antigens in the detection of antibodies against these virulence factors by ELISA in 143 patients with RA and 112 individuals without RA. Significant differences were found in anti-RgpA titers between the two groups and an association with RA was determined (OR 4.09; 95% CI 1.2-13.9), while anti-PPAD did not present differences. The anti-RgpA/anti-PPAD interaction was associated with RA diagnoses (OR 6.63; 95% CI 1.61-27). In addition, the two virulence factors of P. gingivalis were successfully purified and the ELISA was developed, allowing the detection of antibodies against these proteins. Anti-RgpA antibodies and the double positivity of anti-RgpA/anti-PPAD antibodies can be diagnostic markers of RA.Minciencias- Ministerio de Ciencia Tecnología e Innovación. Contrato: 642-2017 Código: 130874455642DoctoradoDoctor en BiotecnologíaMicrobiología Oralxxi, 96 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Doctorado en BiotecnologíaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y salud::616 - EnfermedadesCromatografíaArtritis ReumatoideArthritis, RheumatoidChromatographyPorphyromonas gingivalisRgpAPPADGingipaínasArtritis ReumatoideaPeriodontitisGingipainsRheumatoid arthritisPresencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoidePresence of RgpA, anti-RgpA antibodies and their association with rheumatoid arthritisTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttp://purl.org/redcol/resource_type/TDAdams, B., Nunes, J. M., Page, M. J., Roberts, T., Carr, J., Nell, T. A., Kell, D. B., & Pretorius, E. (2019). Parkinson's Disease: A Systemic Inflammatory Disease Accompanied by Bacterial Inflammagens. Frontiers in aging neuroscience, 11, 210. https://doi.org/10.3389/fnagi.2019.00210Aletaha, D., Neogi, T., Silman, A. J., Funovits, J., Felson, D. T., Bingham, C. O., 3rd, Birnbaum, N. S., Burmester, G. R., Bykerk, V. P., Cohen, M. D., Combe, B., Costenbader, K. H., Dougados, M., Emery, P., Ferraccioli, G., Hazes, J. M., Hobbs, K., Huizinga, T. W., Kavanaugh, A., Kay, J., … Hawker, G. (2010). 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis and rheumatism, 62(9), 2569–2581. https://doi.org/10.1002/art.27584Ambrosio, N., Marín, M. J., Laguna, E., Herrera, D., Sanz, M., & Figuero, E. (2019). Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients. Archives of oral biology, 98, 213–219. https://doi.org/10.1016/j.archoralbio.2018.11.025Arévalo-Caro, C., Romero-Sánchez, C., & Garavito-Rodríguez, E. (2022). Relation between anti-Porphyromonas gingivalis antibody titers and HLA-DRB1 neutral alleles in individuals with rheumatoid arthritis. Acta odontologica Scandinavica, 80(2), 131–139. https://doi.org/10.1080/00016357.2021.1959053Azzi, L., Rania, S., Vinci, R., Spadari, F., Croveri, F., Scognamiglio, C., Farronato, D., Tettamanti, L., Tagliabue, A., Silvestre-Rangil, J., & Bellintani, C. (2017). Periodontal microbioma and rheumatoid arthritis: The role of Porhyromonas gingivalis. Journal of biological regulators and homeostatic agents, 31(2 Suppl 1), 97–103.Bae, S. C., & Lee, Y. H. (2018). Association between anti-Porphyromonas gingivalis antibody, anti-citrullinated protein antibodies, and rheumatoid arthritis: A meta-analysis. Zeitschrift fur Rheumatologie, 77(6), 522–532. https://doi.org/10.1007/s00393-017-0328-yBello-Gualtero, J. M., Lafaurie, G. I., Hoyos, L. X., Castillo, D. M., De-Avila, J., Munevar, J. C., Unriza, S., Londoño, J., Valle-Oñate, R., & Romero-Sánchez, C. (2016). Periodontal Disease in Individuals With a Genetic Risk of Developing Arthritis and Early Rheumatoid Arthritis: A Cross-Sectional Study. Journal of periodontology, 87(4), 346–356. https://doi.org/10.1902/jop.2015.150455Bender, P., Bürgin, W. B., Sculean, A., & Eick, S. (2017). Serum antibody levels against Porphyromonas gingivalis in patients with and without rheumatoid arthritis - a systematic review and meta-analysis. Clinical oral investigations, 21(1), 33–42. https://doi.org/10.1007/s00784-016-1938-5Bereta, G., Goulas, T., Madej, M., Bielecka, E., Solà, M., Potempa, J., & Xavier Gomis-Rüth, F. (2019). Structure, function, and inhibition of a genomic/clinical variant of Porphyromonas gingivalis peptidylarginine deiminase. Protein science: a publication of the Protein Society, 28(3), 478–486. https://doi.org/10.1002/pro.3571Bıyıkoğlu, B., Buduneli, N., Aksu, K., Nalbantsoy, A., Lappin, D. F., Evrenosoğlu, E., & Kinane, D. F. (2013). Periodontal therapy in chronic periodontitis lowers gingival crevicular fluid interleukin-1beta and DAS28 in rheumatoid arthritis patients. Rheumatology international, 33(10), 2607–2616. https://doi.org/10.1007/s00296-013-2781-5Bonfim, M., Mattos, F. F., Ferreira e Ferreira, E., Campos, A. C., & Vargas, A. M. (2013). Social determinants of health and periodontal disease in Brazilian adults: a cross-sectional study. BMC oral health, 13, 22. https://doi.org/10.1186/1472-6831-13-22Borgnakke W. S. (2015). Does Treatment of Periodontal Disease Influence Systemic Disease?. Dental clinics of North America, 59(4), 885–917. https://doi.org/10.1016/j.cden.2015.06.007Botero, J. E., Contreras, A., Lafaurie, G., Jaramillo, A., Betancourt, M., & Arce, R. M. (2007). Occurrence of periodontopathic and superinfecting bacteria in chronic and aggressive periodontitis subjects in a Colombian population. Journal of periodontology, 78(4), 696–704. https://doi.org/10.1902/jop.2007.060129Boutaga, K., van Winkelhoff, A. J., Vandenbroucke-Grauls, C. M., & Savelkoul, P. H. (2003). Comparison of real-time PCR and culture for detection of Porphyromonas gingivalis in subgingival plaque samples. Journal of clinical microbiology, 41(11), 4950–4954. https://doi.org/10.1128/JCM.41.11.4950-4954.2003Cantley, M. D., Haynes, D. R., Marino, V., & Bartold, P. M. (2011). Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. Journal of clinical periodontology, 38(6), 532–541. https://doi.org/10.1111/j.1600-051X.2011.01714.xCastillo-Cañón, J. C., Trujillo-Cáceres, S. J., Bautista-Molano, W., Valbuena-García, A. M., Fernández-Ávila, D. G., & Acuña-Merchán, L. (2021). Rheumatoid arthritis in Colombia: a clinical profile and prevalence from a national registry. Clinical rheumatology, 40(9), 3565–3573. https://doi.org/10.1007/s10067-021-05710-xCastillo, D. M., Castillo, Y., Delgadillo, N. A., Neuta, Y., Lafaurie, G. I., Romero-Sánchez, C., & Castellanos, J. E. (2022). Purification of RgpA from external outer membrane vesicles of Porphyromonas gingivalis. Anaerobe, 77, 102647. https://doi.org/10.1016/j.anaerobe.2022.102647Castillo, Y., Castellanos, J. E., Lafaurie, G. I., & Castillo, D. M. (2022). Porphyromonas gingivalis outer membrane vesicles modulate cytokine and chemokine production by gingipain-dependent mechanisms in human macrophages. Archives of oral biology, 140, 105453. https://doi.org/10.1016/j.archoralbio.2022.105453Ciesielski, O., Biesiekierska, M., Panthu, B., Soszyński, M., Pirola, L., & Balcerczyk, A. (2022). Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives. Cellular and molecular life sciences: CMLS, 79(2), 94. https://doi.org/10.1007/s00018-022-04126-3Chang, K., Yang, S. M., Kim, S. H., Han, K. H., Park, S. J., & Shin, J. I. (2014). Smoking and rheumatoid arthritis. International journal of molecular sciences, 15(12), 22279–22295. https://doi.org/10.3390/ijms151222279Chaparro-Sanabria, J. A., Bautista-Molano, W., Bello-Gualtero, J. M., Chila-Moreno, L., Castillo, D. M., Valle-Oñate, R., Chalem, P., & Romero-Sánchez, C. (2019). Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and their first-degree relatives. International journal of rheumatic diseases, 22(11), 1990–2000. https://doi.org/10.1111/1756-185X.13724Chapple, I., Mealey, B. L., Van Dyke, T. E., Bartold, P. M., Dommisch, H., Eickholz, P., Geisinger, M. L., Genco, R. J., Glogauer, M., Goldstein, M., Griffin, T. J., Holmstrup, P., Johnson, G. K., Kapila, Y., Lang, N. P., Meyle, J., Murakami, S., Plemons, J., Romito, G. A., Shapira, L., … Yoshie, H. (2018). Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. Journal of periodontology, 89 Suppl 1, S74–S84. https://doi.org/10.1002/JPER.17-0719Chen, Y. W., Nagasawa, T., Wara-Aswapati, N., Ushida, Y., Wang, D., Takeuchi, Y., Kobayashi, H., Umeda, M., Inoue, Y., Iwai, T., Ishikawa, I., & Izumi, Y. (2009). Association between periodontitis and anti-cardiolipin antibodies in Buerger disease. Journal of clinical periodontology, 36(10), 830–835. https://doi.org/10.1111/j.1600-051X.2009.01467.xChen, Z., Potempa, J., Polanowski, A., Wikstrom, M., & Travis, J. (1992). Purification and characterization of a 50-kDa cysteine proteinase (gingipain) from Porphyromonas gingivalis. The Journal of biological chemistry, 267(26), 18896–18901.Chiang, H. I., Li, J. R., Liu, C. C., Liu, P. Y., Chen, H. H., Chen, Y. M., Lan, J. L., & Chen, D. Y. (2019). An Association of Gut Microbiota with Different Phenotypes in Chinese Patients with Rheumatoid Arthritis. Journal of clinical medicine, 8(11), 1770. https://doi.org/10.3390/jcm8111770Chou, Y. Y., Lai, K. L., Chen, D. Y., Lin, C. H., & Chen, H. H. (2015). Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide, Population-Based Cohort Study. PloS one, 10(10), e0139693. https://doi.org/10.1371/journal.pone.0139693Crowe, J., Masone, B. S., & Ribbe, J. (1995). One-step purification of recombinant proteins with the 6xHis tag and Ni-NTA resin. Molecular biotechnology, 4(3), 247–258. https://doi.org/10.1007/BF02779018Cush J. J. (2021). Rheumatoid Arthritis: Early Diagnosis and Treatment. The Medical clinics of North America, 105(2), 355–365. https://doi.org/10.1016/j.mcna.2020.10.006Curtis, M. A., Kuramitsu, H. K., Lantz, M., Macrina, F. L., Nakayama, K., Potempa, J., Reynolds, E. C., & Aduse-Opoku, J. (1999). Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis. Journal of periodontal research, 34(8), 464–472. https://doi.org/10.1111/j.1600-0765.1999.tb02282.xDarrah, E., & Andrade, F. (2018). Rheumatoid arthritis and citrullination. Current opinion in rheumatology, 30(1), 72–78. https://doi.org/10.1097/BOR.0000000000000452Dashper, S. G., Mitchell, H. L., Seers, C. A., Gladman, S. L., Seemann, T., Bulach, D. M., Chandry, P. S., Cross, K. J., Cleal, S. M., & Reynolds, E. C. (2017). Porphyromonas gingivalisUses Specific Domain Rearrangements and Allelic Exchange to Generate Diversity in Surface Virulence Factors. Frontiers in microbiology, 8, 48. https://doi.org/10.3389/fmicb.2017.00048Delgado-Angulo, E. K., Bernabé, E., & Marcenes, W. (2016). Ethnic inequalities in periodontal disease among British adults. Journal of clinical periodontology, 43(11), 926–933. https://doi.org/10.1111/jcpe.12605Delgado-Vega, A. M., Martín, J., Granados, J., & Anaya, J. M. (2006). Epidemiología genética de la artritis reumatoide: qué esperar de América Latina? Biomedica: revista del Instituto Nacional de Salud, 26(4), 562–584de Pablo, P., Dietrich, T., & McAlindon, T. E. (2008). Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. The Journal of rheumatology, 35(1), 70–76.de Smit, M., van de Stadt, L. A., Janssen, K. M., Doornbos-van der Meer, B., Vissink, A., van Winkelhoff, A. J., Brouwer, E., Westra, J., & van Schaardenburg, D. (2014). Antibodies against Porphyromonas gingivalis in seropositive arthralgia patients do not predict development of rheumatoid arthritis. Annals of the rheumatic diseases, 73(6), 1277–1279. https://doi.org/10.1136/annrheumdis-2013-204594de Vries, C., Ruacho, G., Kindstedt, E., Potempa, B. A., Potempa, J., Klinge, B., Lundberg, P., Svenungsson, E., & Lundberg, K. (2022). Antibodies to Porphyromonas gingivalis Are Increased in Patients with Severe Periodontitis, and Associate with Presence of Specific Autoantibodies and Myocardial Infarction. Journal of clinical medicine, 11(4), 1008. https://doi.org/10.3390/jcm11041008Derksen, V., Huizinga, T., & van der Woude, D. (2017). The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Seminars in immunopathology, 39(4), 437–446. https://doi.org/10.1007/s00281-017-0627-zDominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., Holsinger, L. J., Arastu-Kapur, S., Kaba, S., Lee, A., Ryder, M. I., Potempa, B., Mydel, P., Hellvard, A., Adamowicz, K., Hasturk, H., … Potempa, J. (2019). Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Science advances, 5(1), eaau3333. https://doi.org/10.1126/sciadv.aau3333Eke, P. I., Page, R. C., Wei, L., Thornton-Evans, G., & Genco, R. J. (2012). Update of the case definitions for population-based surveillance of periodontitis. Journal of periodontology, 83(12), 1449–1454. https://doi.org/10.1902/jop.2012.110664Eke, P. I., Wei, L., Borgnakke, W. S., Thornton-Evans, G., Zhang, X., Lu, H., McGuire, L. C., & Genco, R. J. (2016). Periodontitis prevalence in adults ≥ 65 years of age, in the USA. Periodontology 2000, 72(1), 76–95. https://doi.org/10.1111/prd.12145Eke, P. I., Thornton-Evans, G. O., Wei, L., Borgnakke, W. S., Dye, B. A., & Genco, R. J. (2018). Periodontitis in US Adults: National Health and Nutrition Examination Survey 2009-2014. Journal of the American Dental Association (1939), 149(7), 576–588.e6. https://doi.org/10.1016/j.adaj.2018.04.023Eriksson, K., Fei, G., Lundmark, A., Benchimol, D., Lee, L., Hu, Y., Kats, A., Saevarsdottir, S., Catrina, A. I., Klinge, B., Andersson, A. F., Klareskog, L., Lundberg, K., Jansson, L., & Yucel-Lindberg, T. (2019). Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis. Journal of clinical medicine, 8(5), 630. https://doi.org/10.3390/jcm8050630Federici, M. M., Venkat, K., Bam, N., Patel, K., Dal Monte, P. R., Fernie, B., Hensley, P., Carr, S., Baldoni, J., Truneh, A., & Erickson, J. (2003). Detection and consequences of recombinant protein isoforms: implications for biological potency. Developments in biologicals, 113, 53–114.Firestein, G. S., Budd, R., Gabriel, S. E., O’Dell, J. R., & McInnes, I. B. Kelley’s Textbook of Rheumatology: Expert Consult Premium Edition. Elsevier Health Sciences; 9th Ed. Páginas 1059-1074; 2013. ISBN 978-1-4377-1738-9.Firestein, G. S., & McInnes, I. B. (2017). Immunopathogenesis of Rheumatoid Arthritis. Immunity, 46(2), 183–196. https://doi.org/10.1016/j.immuni.2017.02.006Fisher, B. A., Cartwright, A. J., Quirke, A. M., de Pablo, P., Romaguera, D., Panico, S., Mattiello, A., Gavrila, D., Navarro, C., Sacerdote, C., Vineis, P., Tumino, R., Lappin, D. F., Apatzidou, D., Culshaw, S., Potempa, J., Michaud, D. S., Riboli, E., & Venables, P. J. (2015). Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. BMC musculoskeletal disorders, 16, 331. https://doi.org/10.1186/s12891-015-0792-yFitzpatrick, R. E., Wijeyewickrema, L. C., & Pike, R. N. (2009). The gingipains: scissors and glue of the periodontal pathogen, Porphyromonas gingivalis. Future microbiology, 4(4), 471–487. https://doi.org/10.2217/fmb.09.18Fransen J., Stucki G., van Riel PLCM. (2003). Rheumatoid arthritis measures: Disease Activity Score (DAS), Disease Activity Score-28 (DAS28), Rapid Assessment of Disease Activity in Rheumatology (RADAR), and Rheumatoid Arthritis Disease Activity Index (RADAI). Arthritis Rheum, 49 (5S), S214–224. https://doi.org/:10.1002/art.11407Gabriel S. E. (2001). The epidemiology of rheumatoid arthritis. Rheumatic diseases clinics of North America, 27(2), 269–281. https://doi.org/10.1016/s0889-857x(05)70201-5Gabarrini, G., Chlebowicz, M. A., Vega Quiroz, M. E., Veloo, A., Rossen, J., Harmsen, H., Laine, M. L., van Dijl, J. M., & van Winkelhoff, A. J. (2018). Conserved Citrullinating Exoenzymes in Porphyromonas Species. Journal of dental research, 97(5), 556–562. https://doi.org/10.1177/0022034517747575García, J., Santana, Z., Zumalacárregui, L., Quintana, M., González, D., Furrazola, G., Cruz, O. (2013). Estrategias de obtención de proteínas recombinantes en Escherichia coli. VacciMonitor, 22(2):30-39.Gawron, K., Bereta, G., Nowakowska, Z., Lazarz-Bartyzel, K., Lazarz, M., Szmigielski, B., Mizgalska, D., Buda, A., Koziel, J., Oruba, Z., Chomyszyn-Gajewska, M., & Potempa, J. (2014). Peptidylarginine deiminase from Porphyromonas gingivalis contributes to infection of gingival fibroblasts and induction of prostaglandin E2 -signaling pathway. Molecular oral microbiology, 29(6), 321–332. https://doi.org/10.1111/omi.12081Ghayoumi, N., Chen, C., & Slots, J. (2002). Dialister pneumosintes, a new putative periodontal pathogen. Journal of periodontal research, 37(1), 75–78. https://doi.org/10.1034/j.1600-0765.2002.05019.xGiles, J. T., Fert-Bober, J., Park, J. K., Bingham, C. O., 3rd, Andrade, F., Fox-Talbot, K., Pappas, D., Rosen, A., van Eyk, J., Bathon, J. M., & Halushka, M. K. (2012). Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study. Arthritis research & therapy, 14(1), R39. https://doi.org/10.1186/ar3752Gómez-Bañuelos, E., Mukherjee, A., Darrah, E., & Andrade, F. (2019). Rheumatoid Arthritis-Associated Mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Journal of clinical medicine, 8(9), 1309. https://doi.org/10.3390/jcm8091309Gorasia, D. G., Lunar Silva, I., Butler, C. A., Chabalier, M., Doan, T., Cascales, E., Veith, P. D., & Reynolds, E. C. (2022). Protein Interactome Analysis of the Type IX Secretion System Identifies PorW as the Missing Link between the PorK/N Ring Complex and the Sov Translocon. Microbiology spectrum, 10(1), e0160221. https://doi.org/10.1128/spectrum.01602-21Gorasia, D. G., Veith, P. D., Chen, D., Seers, C. A., Mitchell, H. A., Chen, Y. Y., Glew, M. D., Dashper, S. G., & Reynolds, E. C. (2015). Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism. PLoS pathogens, 11(9), e1005152. https://doi.org/10.1371/journal.ppat.1005152Goulas, T., Mizgalska, D., Garcia-Ferrer, I., Kantyka, T., Guevara, T., Szmigielski, B., Sroka, A., Millán, C., Usón, I., Veillard, F., Potempa, B., Mydel, P., Solà, M., Potempa, J., & Gomis-Rüth, F. X. (2015). Structure and mechanism of a bacterial host-protein citrullinating virulence factor, Porphyromonas gingivalis peptidylarginine deiminase. Scientific reports, 5, 11969. https://doi.org/10.1038/srep11969Graves D. (2008). Cytokines that promote periodontal tissue destruction. Journal of periodontology, 79(8 Suppl), 1585–1591. https://doi.org/10.1902/jop.2008.080183Guevara, T., Rodríguez-Banqueri, A., Lasica, A. M., Ksiazek, M., Potempa, B. A., Potempa, J., & Gomis-Rüth, F. X. (2019). Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor. Scientific reports, 9(1), 4935. https://doi.org/10.1038/s41598-019-41354-3Gully, N., Bright, R., Marino, V., Marchant, C., Cantley, M., Haynes, D., Butler, C., Dashper, S., Reynolds, E., & Bartold, M. (2014). Porphyromonas gingivalis peptidylarginine deiminase, a key contributor in the pathogenesis of experimental periodontal disease and experimental arthritis. PloS one, 9(6), e100838. https://doi.org/10.1371/journal.pone.0100838Hajishengallis G. (2015). Periodontitis: from microbial immune subversion to systemic inflammation. Nature reviews. Immunology, 15(1), 30–44. https://doi.org/10.1038/nri3785Hajishengallis, G., Darveau, R. P., & Curtis, M. A. (2012). The keystone-pathogen hypothesis. Nature reviews. Microbiology, 10(10), 717–725. https://doi.org/10.1038/nrmicro2873Hamamoto, Y., Ouhara, K., Munenaga, S., Shoji, M., Ozawa, T., Hisatsune, J., Kado, I., Kajiya, M., Matsuda, S., Kawai, T., Mizuno, N., Fujita, T., Hirata, S., Tanimoto, K., Nakayama, K., Kishi, H., Sugiyama, E., & Kurihara, H. (2020). Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model. Arthritis research & therapy, 22(1), 249. https://doi.org/10.1186/s13075-020-02348-zHedström, A. K., Stawiarz, L., Klareskog, L., & Alfredsson, L. (2018). Smoking and susceptibility to rheumatoid arthritis in a Swedish population-based case-control study. European journal of epidemiology, 33(4), 415–423. https://doi.org/10.1007/s10654-018-0360-5Heredia-P, A. M., Lafaurie, G. I., Bautista-Molano, W., Trujillo, T. G., Chalem-Choueka, P., Bello-Gualtero, J. M., Pacheco-Tena, C., Chila-Moreno, L., & Romero-Sánchez, C. (2019). Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: a cohort study. BMC oral health, 19(1), 240. https://doi.org/10.1186/s12903-019-0939-6Hirai, K., Yamaguchi-Tomikawa, T., Eguchi, T., Maeda, H., & Takashiba, S. (2020). Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis. Frontiers in immunology, 11, 1017. https://doi.org/10.3389/fimmu.2020.01017Hitchon, C. A., Chandad, F., Ferucci, E. D., Willemze, A., Ioan-Facsinay, A., van der Woude, D., Markland, J., Robinson, D., Elias, B., Newkirk, M., Toes, R. M., Huizinga, T. W., & El-Gabalawy, H. S. (2010). Antibodies to Porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. The Journal of rheumatology, 37(6), 1105–1112. https://doi.org/10.3899/jrheum.091323Huck, O., You, J., Han, X., Cai, B., Panek, J., & Amar, S. (2018). Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model. Infection and immunity, 86(9), e00356-18. https://doi.org/10.1128/IAI.00356-18Imamura T. (2003)a. The role of gingipains in the pathogenesis of periodontal disease. Journal of periodontology, 74(1), 111–118. https://doi.org/10.1902/jop.2003.74.1.111Imamura, T., Travis, J., & Potempa, J. (2003)b. The biphasic virulence activities of gingipains: activation and inactivation of host proteins. Current protein & peptide science, 4(6), 443–450. https://doi.org/10.2174/1389203033487027Ingalagi, P., Bhat, K. G., Kulkarni, R. D., Kotrashetti, V. S., Kumbar, V., & Kugaji, M. (2022). Detection and comparison of prevalence of Porphyromonas gingivalis through culture and Real Time-polymerase chain reaction in subgingival plaque samples of chronic periodontitis and healthy individuals. Journal of oral and maxillofacial pathology: JOMFP, 26(2), 288. https://doi.org/10.4103/jomfp.jomfp_163_21Jang, S., Kwon, E. J., & Lee, J. J. (2022). Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells. International journal of molecular sciences, 23(2), 905. https://doi.org/10.3390/ijms23020905Jasemi, S., Erre, G. L., Cadoni, M. L., Bo, M., & Sechi, L. A. (2021). Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients. Journal of clinical medicine, 10(21), 5153. https://doi.org/10.3390/jcm10215153Jenning, M., Marklein, B., Ytterberg, J., Zubarev, R. A., Joshua, V., van Schaardenburg, D., van de Stadt, L., Catrina, A. I., Nonhoff, U., Häupl, T., Konthur, Z., Burmester, G. R., & Skriner, K. (2020). Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Annals of the rheumatic diseases, 79(9), 1194–1202. https://doi.org/10.1136/annrheumdis-2019-216919Jeong, H., Kim, H. J., & Lee, S. J. (2015). Complete Genome Sequence of Escherichia coli Strain BL21. Genome announcements, 3(2), e00134-15. https://doi.org/10.1128/genomeA.00134-15Jia, L., Han, N., Du, J., Guo, L., Luo, Z., & Liu, Y. (2019). Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors. Frontiers in cellular and infection microbiology, 9, 262. https://doi.org/10.3389/fcimb.2019.00262Johansson, L., Sherina, N., Kharlamova, N., Potempa, B., Larsson, B., Israelsson, L., Potempa, J., Rantapää-Dahlqvist, S., & Lundberg, K. (2016). Concentration of antibodies against Porphyromonas gingivalis increased before the onset of symptoms of rheumatoid arthritis. Arthritis research & therapy, 18(1), 201. https://doi.org/10.1186/s13075-016-1100-4Jung, H., Jung, S. M., Rim, Y. A., Park, N., Nam, Y., Lee, J., Park, S. H., & Ju, J. H. (2017). Arthritic role of Porphyromonas gingivalis in collagen-induced arthritis mice. PloS one, 12(11), e0188698. https://doi.org/10.1371/journal.pone.0188698Kadowaki, T., Yoneda, M., Okamoto, K., Maeda, K., & Yamamoto, K. (1994). Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis. The Journal of biological chemistry, 269(33), 21371–21378.Kharlamova, N., Jiang, X., Sherina, N., Potempa, B., Israelsson, L., Quirke, A. M., Eriksson, K., Yucel-Lindberg, T., Venables, P. J., Potempa, J., Alfredsson, L., & Lundberg, K. (2016). Antibodies to Porphyromonas gingivalis Indicate Interaction Between Oral Infection, Smoking, and Risk Genes in Rheumatoid Arthritis Etiology. Arthritis & rheumatology (Hoboken, N.J.), 68(3), 604–613. https://doi.org/10.1002/art.39491Klareskog, L., Widhe, M., Hermansson, M., & Rönnelid, J. (2008). Antibodies to citrullinated proteins in arthritis: pathology and promise. Current opinion in rheumatology, 20(3), 300–305. https://doi.org/10.1097/BOR.0b013e3282fbd22aKonig, M. F., Paracha, A. S., Moni, M., Bingham, C. O., 3rd, & Andrade, F. (2015). Defining the role of Porphyromonas gingivalis peptidylarginine deiminase (PPAD) in rheumatoid arthritis through the study of PPAD biology. Annals of the rheumatic diseases, 74(11), 2054–2061. https://doi.org/10.1136/annrheumdis-2014-205385Kwon, T., Lamster, I. B., & Levin, L. (2021). Current Concepts in the Management of Periodontitis. International dental journal, 71(6), 462–476. https://doi.org/10.1111/idj.12630Kuramitsu H. K. (1998). Proteases of Porphyromonas gingivalis: what don't they do?. Oral microbiology and immunology, 13(5), 263–270. https://doi.org/10.1111/j.1399-302x.1998.tb00706.xKrutyhołowa, A., Strzelec, K., Dziedzic, A., Bereta, G. P., Łazarz-Bartyzel, K., Potempa, J., & Gawron, K. (2022). Host and bacterial factors linking periodontitis and rheumatoid arthritis. Frontiers in immunology, 13, 980805. https://doi.org/10.3389/fimmu.2022.980805Lafaurie, G. I., Neuta, Y., Ríos, R., Pacheco-Montealegre, M., Pianeta, R., Castillo, D. M., Herrera, D., Reyes, J., Diaz, L., Castillo, Y., Sanz, M., & Iniesta, M. (2022). Differences in the subgingival microbiome according to stage of periodontitis: A comparison of two geographic regions. PloS one, 17(8), e0273523. https://doi.org/10.1371/journal.pone.0273523Lafaurie, G.I., Castillo, D.M., Iniesta, M., Sanz, M., Gómez, L. A., Castillo, Y., Pianeta, R., Delgadillo, N.A., Neuta, Y., Diaz-Báez, D., Herrera, D. (2023). Differential analysis of culturable and unculturable subgingival target microorganisms according to the stages of periodontitis. Clinical Oral Investigations (Aceptado para publicación).Lafaurie, G. I., Mayorga-Fayad, I., Torres, M. F., Castillo, D. M., Aya, M. R., Barón, A., & Hurtado, P. A. (2007a). Periodontopathic microorganisms in peripheric blood after scaling and root planing. Journal of clinical periodontology, 34(10), 873–879. https://doi.org/10.1111/j.1600-051X.2007.01125.xLafaurie, G. I., Contreras, A., Barón, A., Botero, J., Mayorga-Fayad, I., Jaramillo, A., Giraldo, A., González, F., Mantilla, S., Botero, A., Archila, L. H., Díaz, A., Chacón, T., Castillo, D. M., Betancourt, M., Del Rosario Aya, M., & Arce, R. (2007b). Demographic, clinical, and microbial aspects of chronic and aggressive periodontitis in Colombia: a multicenter study. Journal of periodontology, 78(4), 629–639. https://doi.org/10.1902/jop.2007.060187Laugisch, O., Wong, A., Sroka, A., Kantyka, T., Koziel, J., Neuhaus, K., Sculean, A., Venables, P. J., Potempa, J., Möller, B., & Eick, S. (2016). Citrullination in the periodontium--a possible link between periodontitis and rheumatoid arthritis. Clinical oral investigations, 20(4), 675–683. https://doi.org/10.1007/s00784-015-1556-7Lee, J. Y., Choi, I. A., Kim, J. H., Kim, K. H., Lee, E. Y., Lee, E. B., Lee, Y. M., & Song, Y. W. (2015). Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA. BMC musculoskeletal disorders, 16, 190. https://doi.org/10.1186/s12891-015-0647-6Leech, M. T., & Bartold, P. M. (2015). The association between rheumatoid arthritis and periodontitis. Best practice & research. Clinical rheumatology, 29(2), 189–201. https://doi.org/10.1016/j.berh.2015.03.001Li, Y., Guo, R., Oduro, P. K., Sun, T., Chen, H., Yi, Y., Zeng, W., Wang, Q., Leng, L., Yang, L., & Zhang, J. (2022). The Relationship Between Porphyromonas gingivalis and Rheumatoid Arthritis: A Meta-Analysis. Frontiers in cellular and infection microbiology, 12, 956417. https://doi.org/10.3389/fcimb.2022.956417Li, N., & Collyer, C. A. (2011). Gingipains from Porphyromonas gingivalis- Complex domain structures confer diverse functions. European journal of microbiology & immunology, 1(1), 41–58. https://doi.org/10.1556/EuJMI.1.2011.1.7Liu, X., Zou, Q., Zeng, B., Fang, Y., & Wei, H. (2013). Analysis of fecal Lactobacillus community structure in patients with early rheumatoid arthritis. Current microbiology, 67(2), 170–176. https://doi.org/10.1007/s00284-013-0338-1Loutan, L., Alpizar-Rodriguez, D., Courvoisier, D. S., Finckh, A., Mombelli, A., & Giannopoulou, C. (2019). Periodontal status correlates with anti-citrullinated protein antibodies in first-degree relatives of individuals with rheumatoid arthritis. Journal of clinical periodontology, 46(7), 690–698. https://doi.org/10.1111/jcpe.13117Lübcke, P. M., Ebbers, M., Volzke, J., Bull, J., Kneitz, S., Engelmann, R., Lang, H., Kreikemeyer, B., & Müller-Hilke, B. (2019). Periodontal treatment prevents arthritis in mice and methotrexate ameliorates periodontal bone loss. Scientific reports, 9(1), 8128. https://doi.org/10.1038/s41598-019-44512-9Ma, K. S., Chiang, C. H., Chen, Y. W., & Wang, L. T. (2021). Correspondence to 'Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production'. Annals of the rheumatic diseases, annrheumdis-2020-219255. Advance online publication. https://doi.org/10.1136/annrheumdis-2020-219255Mangat, P., Wegner, N., Venables, P. J., & Potempa, J. (2010). Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?. Arthritis research & therapy, 12(3), 209. https://doi.org/10.1186/ar3000Margetts, M. B., Barr, I. G., & Webb, E. A. (2000). Overexpression, purification, and refolding of a Porphyromonas gingivalis cysteine protease from Escherichia coli. Protein expression and purification, 18(3), 262–268. https://doi.org/10.1006/prep.2000.1193Mantri, C. K., Chen, C. H., Dong, X., Goodwin, J. S., Pratap, S., Paromov, V., & Xie, H. (2015). Fimbriae-mediated outer membrane vesicle production and invasion of Porphyromonas gingivalis. MicrobiologyOpen, 4(1), 53–65. https://doi.org/10.1002/mbo3.221Marchesan, J. T., Gerow, E. A., Schaff, R., Taut, A. D., Shin, S. Y., Sugai, J., Brand, D., Burberry, A., Jorns, J., Lundy, S. K., Nuñez, G., Fox, D. A., & Giannobile, W. V. (2013). Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis. Arthritis research & therapy, 15(6), R186. https://doi.org/10.1186/ar4376Maresz, K. J., Hellvard, A., Sroka, A., Adamowicz, K., Bielecka, E., Koziel, J., Gawron, K., Mizgalska, D., Marcinska, K. A., Benedyk, M., Pyrc, K., Quirke, A. M., Jonsson, R., Alzabin, S., Venables, P. J., Nguyen, K. A., Mydel, P., & Potempa, J. (2013). Porphyromonas gingivalis facilitates the development and progression of destructive arthritis through its unique bacterial peptidylarginine deiminase (PAD). PLoS pathogens, 9(9), e1003627. https://doi.org/10.1371/journal.ppat.1003627Martínez-Rivera, J. I., Xibillé-Friedmann, D. X., González-Christen, J., de la Garza-Ramos, M. A., Carrillo-Vázquez, S. M., & Montiel-Hernández, J. L. (2017). Salivary ammonia levels and Tannerella forsythia are associated with rheumatoid arthritis: A cross sectional study. Clinical and experimental dental research, 3(3), 107–114. https://doi.org/10.1002/cre2.68Mayorga-Fayad, I., Lafaurie, G. I., Contreras, A., Castillo, D. M., Barón, A., & Aya, M. (2007). Microflora subgingival en periodontitis crónica y agresiva en Bogotá, Colombia: un acercamiento epidemiológico. Biomedica : revista del Instituto Nacional de Salud, 27(1), 21–33.McGraw, W. T., Potempa, J., Farley, D., & Travis, J. (1999). Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infection and immunity, 67(7), 3248–3256. https://doi.org/10.1128/IAI.67.7.3248-3256.1999Ministerio de salud. Estudio Nacional En Salud Bucal (ENSAB IV). Bogotá, Colombia. 2014;4.Consultado en: https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/VS/PP/ENSAB-IV-Situacion-Bucal-Actual.pdfMikuls, T. R., Payne, J. B., Yu, F., Thiele, G. M., Reynolds, R. J., Cannon, G. W., Markt, J., McGowan, D., Kerr, G. S., Redman, R. S., Reimold, A., Griffiths, G., Beatty, M., Gonzalez, S. M., Bergman, D. A., Hamilton, B. C., 3rd, Erickson, A. R., Sokolove, J., Robinson, W. H., Walker, C., … O'Dell, J. R. (2014). Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N.J.), 66(5), 1090–1100. https://doi.org/10.1002/art.38348Montgomery, A. B., Kopec, J., Shrestha, L., Thezenas, M. L., Burgess-Brown, N. A., Fischer, R., Yue, W. W., & Venables, P. J. (2016). Crystal structure of Porphyromonas gingivalis peptidylarginine deiminase: implications for autoimmunity in rheumatoid arthritis. Annals of the rheumatic diseases, 75(6), 1255–1261. https://doi.org/10.1136/annrheumdis-2015-207656Moen, K., Brun, J. G., Madland, T. M., Tynning, T., & Jonsson, R. (2003). Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients. Clinical and diagnostic laboratory immunology, 10(6), 1043–1050. https://doi.org/10.1128/cdli.10.6.1043-1050.2003Morales, L., Velandia, M. L., Calderon, M. A., Castellanos, J. E., & Chaparro-Olaya, J. (2017). Anticuerpos policlonales contra la proteína recombinante NS3 del virus del dengue. Biomedica: revista del Instituto Nacional de Salud, 37(1), 131–140. https://doi.org/10.7705/biomedica.v37i1.3249Moses, T., & Holland, P. W. (2010). A comparison of statistical selection strategies for univariate and bivariate log-linear models. The British journal of mathematical and statistical psychology, 63(Pt 3), 557–574. https://doi.org/10.1348/000711009X478580Muñoz-Atienza, E., Flak, M. B., Sirr, J., Paramonov, N. A., Aduse-Opoku, J., Pitzalis, C., & Curtis, M. A. (2020). The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis. Journal of dental research, 99(4), 456–462. https://doi.org/10.1177/0022034519898144Munenaga, S., Ouhara, K., Hamamoto, Y., Kajiya, M., Takeda, K., Yamasaki, S., Kawai, T., Mizuno, N., Fujita, T., Sugiyama, E., & Kurihara, H. (2018). The involvement of C5a in the progression of experimental arthritis with Porphyromonas gingivalis infection in SKG mice. Arthritis research & therapy, 20(1), 247. https://doi.org/10.1186/s13075-018-1744-3Nakao, R., Takashiba, S., Kosono, S., Yoshida, M., Watanabe, H., Ohnishi, M., & Senpuku, H. (2014). Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses. Microbes and infection, 16(1), 6–16. https://doi.org/10.1016/j.micinf.2013.10.005Nakayama, K., Kadowaki, T., Okamoto, K., & Yamamoto, K. (1995). Construction and characterization of arginine-specific cysteine proteinase (Arg-gingipain)-deficient mutants of Porphyromonas gingivalis. Evidence for significant contribution of Arg-gingipain to virulence. The Journal of biological chemistry, 270(40), 23619–23626. https://doi.org/10.1074/jbc.270.40.23619Nemoto, T. K., & Ohara-Nemoto, Y. (2016). Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism. The Japanese dental science review, 52(1), 22–29. https://doi.org/10.1016/j.jdsr.2015.08.002Nunes, J. M., Fillis, T., Page, M. J., Venter, C., Lancry, O., Kell, D. B., Windberger, U., & Pretorius, E. (2020). Gingipain R1 and Lipopolysaccharide From Porphyromonas gingivalis Have Major Effects on Blood Clot Morphology and Mechanics. Frontiers in immunology, 11, 1551. https://doi.org/10.3389/fimmu.2020.01551Okada, M., Kobayashi, T., Ito, S., Yokoyama, T., Abe, A., Murasawa, A., & Yoshie, H. (2013). Periodontal treatment decreases levels of antibodies to Porphyromonas gingivalis and citrulline in patients with rheumatoid arthritis and periodontitis. Journal of periodontology, 84(12), e74–e84. https://doi.org/10.1902/jop.2013.130079Okada, M., Kobayashi, T., Ito, S., Yokoyama, T., Komatsu, Y., Abe, A., Murasawa, A., & Yoshie, H. (2011). Antibody responses to periodontopathic bacteria in relation to rheumatoid arthritis in Japanese adults. Journal of periodontology, 82(10), 1433–1441. https://doi.org/10.1902/jop.2011.110020Olsen, I., Singhrao, S. K., & Potempa, J. (2018). Citrullination as a plausible link to periodontitis, rheumatoid arthritis, atherosclerosis and Alzheimer's disease. Journal of oral microbiology, 10(1), 1487742. https://doi.org/10.1080/20002297.2018.1487742Owczarek, B., Gerszberg, A., & Hnatuszko-Konka, K. (2019). A Brief Reminder of Systems of Production and Chromatography-Based Recovery of Recombinant Protein Biopharmaceuticals. BioMed research international, 2019, 4216060. https://doi.org/10.1155/2019/4216060Padyukov L. (2022). Genetics of rheumatoid arthritis. Seminars in immunopathology, 44(1), 47–62. https://doi.org/10.1007/s00281-022-00912-0Page, R. C., & Eke, P. I. (2007). Case definitions for use in population-based surveillance of periodontitis. Journal of periodontology, 78(7 Suppl), 1387–1399. https://doi.org/10.1902/jop.2007.060264Pathirana, R. D., O'Brien-Simpson, N. M., Veith, P. D., Riley, P. F., & Reynolds, E. C. (2006). Characterization of proteinase-adhesin complexes of Porphyromonas gingivalis. Microbiology (Reading, England), 152(Pt 8), 2381–2394. https://doi.org/10.1099/mic.0.28787-0Pathirana, R. D., O'Brien-Simpson, N. M., Brammar, G. C., Slakeski, N., & Reynolds, E. C. (2007). Kgp and RgpB, but not RgpA, are important for Porphyromonas gingivalis virulence in the murine periodontitis model. Infection and immunity, 75(3), 1436–1442. https://doi.org/10.1128/IAI.01627-06Pianta, A., Arvikar, S., Strle, K., Drouin, E. E., Wang, Q., Costello, C. E., & Steere, A. C. (2017). Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.), 69(5), 964–975. https://doi.org/10.1002/art.40003Posada-López, A., Botero, J. E., Pineda-Tamayo, R. A., & Agudelo-Suárez, A. A. (2022). The Effect of Periodontal Treatment on Clinical and Biological Indicators, Quality of Life, and Oral Health in Rheumatoid Arthritis Patients: A Quasi-Experimental Study. International journal of environmental research and public health, 19(3), 1789. https://doi.org/10.3390/ijerph19031789Potempa, J., Mydel, P., & Koziel, J. (2017). The case for periodontitis in the pathogenesis of rheumatoid arthritis. Nature reviews. Rheumatology, 13(10), 606–620. https://doi.org/10.1038/nrrheum.2017.132Potempa J, Nguyen KA (2007). Purification and characterization of gingipains. Curr Protoc Protein Sci. Chapter 21.Potempa, J., Sroka, A., Imamura, T., & Travis, J. (2003). Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes. Current protein & peptide science, 4(6), 397–407. https://doi.org/10.2174/1389203033487036Potempa, J., Pavloff, N., & Travis, J. (1995)a. Porphyromonas gingivalis: a proteinase/gene accounting audit. Trends in microbiology, 3(11), 430–434. https://doi.org/10.1016/s0966-842x(00)88996-9Potempa, J., Pike, R., & Travis, J. (1995)b. The multiple forms of trypsin-like activity present in various strains of Porphyromonas gingivalis are due to the presence of either Arg-gingipain or Lys-gingipain. Infection and immunity, 63(4), 1176–1182. https://doi.org/10.1128/iai.63.4.1176-1182.1995Puszczewicz, M., & Iwaszkiewicz, C. (2011). Role of anti-citrullinated protein antibodies in diagnosis and prognosis of rheumatoid arthritis. Archives of medical science: AMS, 7(2), 189–194. https://doi.org/10.5114/aoms.2011.22067Qiao, Y., Wang, Z., Li, Y., Han, Y., Zhou, Y., & Cao, X. (2020). Rheumatoid arthritis risk in periodontitis patients: A systematic review and meta-analysis. Joint bone spine, 87(6), 556–564. https://doi.org/10.1016/j.jbspin.2020.04.024Qin, B., Yang, M., Fu, H., Ma, N., Wei, T., Tang, Q., Hu, Z., Liang, Y., Yang, Z., & Zhong, R. (2015). Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis. Arthritis research & therapy, 17(1), 86. https://doi.org/10.1186/s13075-015-0601-xQuirke, A. M., Lugli, E. B., Wegner, N., Hamilton, B. C., Charles, P., Chowdhury, M., Ytterberg, A. J., Zubarev, R. A., Potempa, J., Culshaw, S., Guo, Y., Fisher, B. A., Thiele, G., Mikuls, T. R., & Venables, P. J. (2014). Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis. Annals of the rheumatic diseases, 73(1), 263–269. https://doi.org/10.1136/annrheumdis-2012-202726Rahajoe, P. S., de Smit, M., Schuurmans, G., Raveling-Eelsing, E., Kertia, N., Vissink, A., & Westra, J. (2020). Increased IgA anti-citrullinated protein antibodies in the periodontal inflammatory exudate of healthy individuals compared to rheumatoid arthritis patients. Journal of clinical periodontology, 47(5), 552–560. https://doi.org/10.1111/jcpe.13277Repeke, C. E., Cardoso, C. R., Claudino, M., Silveira, E. M., Trombone, A. P., Campanelli, A. P., Silva, J. S., Martins, W., Jr, & Garlet, G. P. (2012). Non-inflammatory destructive periodontal disease: a clinical, microbiological, immunological and genetic investigation. Journal of applied oral science : revista FOB, 20(1), 113–121. https://doi.org/10.1590/s1678-77572012000100020Richards D. (2014). Review finds that severe periodontitis affects 11% of the world population. Evidence-based dentistry, 15(3), 70–71. https://doi.org/10.1038/sj.ebd.6401037Rodríguez, J., Lafaurie, G. I., Bautista-Molano, W., Chila-Moreno, L., Bello-Gualtero, J. M., & Romero-Sánchez, C. (2021). Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study. Clinical oral investigations, 25(4), 1685–1695. https://doi.org/10.1007/s00784-020-03469-0Rodríguez, S. B., Stitt, B. L., & Ash, D. E. (2009). Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization. Archives of biochemistry and biophysics, 488(1), 14–22. https://doi.org/10.1016/j.abb.2009.06.010Röhner, E., Detert, J., Kolar, P., Hocke, A., N'Guessan, P., Matziolis, G., Kanitz, V., Bernimoulin, J. P., Kielbassa, A., Burmester, G. R., Buttgereit, F., & Pischon, N. (2010). Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis. Calcified tissue international, 87(4), 333–340. https://doi.org/10.1007/s00223-010-9389-5Romero-Sánchez, C., Rodríguez, C., Santos-Moreno, P., Mesa, A. M., Lafaurie, G. I., Giraldo-Q, S., De-Avila, J., Castillo, D. M., Duran, M., Chalem, P. C., Bello Gualtero, J. M., & Valle-Oñate, R. (2017). Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?. Current rheumatology reviews, 13(2), 139–151. https://doi.org/10.2174/1573397113666170407161520Rovas, A., Puriene, A., Punceviciene, E., Butrimiene, I., Stuopelyte, K., & Jarmalaite, S. (2021). Associations of periodontal status in periodontitis and rheumatoid arthritis patients. Journal of periodontal & implant science, 51(2), 124–134. https://doi.org/10.5051/jpis.2006060303Sato, K., Takahashi, N., Kato, T., Matsuda, Y., Yokoji, M., Yamada, M., Nakajima, T., Kondo, N., Endo, N., Yamamoto, R., Noiri, Y., Ohno, H., & Yamazaki, K. (2017). Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system. Scientific reports, 7(1), 6955. https://doi.org/10.1038/s41598-017-07196-7Schenkein, H. A., Bradley, J. L., & Purkall, D. B. (2013). Anticardiolipin in Porphyromonas gingivalis antisera causes fetal loss in mice. Journal of dental research, 92(9), 814–818. https://doi.org/10.1177/0022034513497959Schmalz, G., Noack, S., Patschan, S., Patschan, D., Müller, G. A., Rupprecht, A., Schmickler, J., Haak, R., & Ziebolz, D. (2020). Disease activity, morning stiffness and missing teeth are associated with oral health-related quality of life in individuals with rheumatoid arthritis. Clinical oral investigations, 24(10), 3559–3566. https://doi.org/10.1007/s00784-020-03226-3Schmickler, J., Rupprecht, A., Patschan, S., Patschan, D., Müller, G. A., Haak, R., Mausberg, R. F., Schmalz, G., Kottmann, T., & Ziebolz, D. (2017). Cross-Sectional Evaluation of Periodontal Status and Microbiologic and Rheumatoid Parameters in a Large Cohort of Patients With Rheumatoid Arthritis. Journal of periodontology, 88(4), 368–379. https://doi.org/10.1902/jop.2016.160355Seers, C. A., Mahmud, A., Huq, N. L., Cross, K. J., & Reynolds, E. C. (2020). Porphyromonas gingivalis laboratory strains and clinical isolates exhibit different distribution of cell surface and secreted gingipains. Journal of oral microbiology, 13(1), 1858001. https://doi.org/10.1080/20002297.2020.1858001Serrano, C., & Suarez, E. (2019). Prevalence of Severe Periodontitis in a Colombian Adult Population. Journal of the International Academy of Periodontology, 21(2), 53–62.Shimada, A., Kobayashi, T., Ito, S., Okada, M., Murasawa, A., Nakazono, K., & Yoshie, H. (2016). Expression of anti-Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase-4 in patients with rheumatoid arthritis and periodontitis. Journal of periodontal research, 51(1), 103–111. https://doi.org/10.1111/jre.12288Sippert, E. Â., de Oliveira e Silva, C., Ayo, C. M., Marques, S. B., Visentainer, J. E., & Sell, A. M. (2015). HLA Haplotypes and Genotypes Frequencies in Brazilian Chronic Periodontitis Patients. Mediators of inflammation, 2015, 481656. https://doi.org/10.1155/2015/481656Slots J. (1987). Detection of colonies of Bacteroides gingivalis by a rapid fluorescence assay for trypsin-like activity. Oral microbiology and immunology, 2(3), 139–141. https://doi.org/10.1111/j.1399-302x.1987.tb00279.xSlots, J., Bragd, L., Wikström, M., & Dahlén, G. (1986). The occurrence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Bacteroides intermedius in destructive periodontal disease in adults. Journal of clinical periodontology, 13(6), 570–577. https://doi.org/10.1111/j.1600-051x.1986.tb00849.xSmalley, J. W., & Olczak, T. (2017). Heme acquisition mechanisms of Porphyromonas gingivalis strategies used in a polymicrobial community in a heme-limited host environment. Molecular oral microbiology, 32(1), 1–23. https://doi.org/10.1111/omi.12149Smolen, J. S., Aletaha, D., & McInnes, I. B. (2016). Rheumatoid arthritis. Lancet (London, England), 388(10055), 2023–2038. https://doi.org/10.1016/S0140-6736(16)30173-8Stobernack, T., Glasner, C., Junker, S., Gabarrini, G., de Smit, M., de Jong, A., Otto, A., Becher, D., van Winkelhoff, A. J., & van Dijl, J. M. (2016). Extracellular Proteome and Citrullinome of the Oral Pathogen Porphyromonas gingivalis. Journal of proteome research, 15(12), 4532–4543. https://doi.org/10.1021/acs.jproteome.6b00634Structural Genomics Consortium, China Structural Genomics Consortium, Northeast Structural Genomics Consortium, Gräslund, S., Nordlund, P., Weigelt, J., Hallberg, B. M., Bray, J., Gileadi, O., Knapp, S., Oppermann, U., Arrowsmith, C., Hui, R., Ming, J., dhe-Paganon, S., Park, H. W., Savchenko, A., Yee, A., Edwards, A., Vincentelli, R., … Gunsalus, K. C. (2008). Protein production and purification. Nature methods, 5(2), 135–146. https://doi.org/10.1038/nmeth.f.202Sun, J., Zheng, Y., Bian, X., Ge, H., Wang, J., & Zhang, Z. (2021). Non-surgical periodontal treatment improves rheumatoid arthritis disease activity: a meta-analysis. Clinical oral investigations, 25(8), 4975–4985. https://doi.org/10.1007/s00784-021-03807-wThermofisher. (2020). One Shot™ TOP10 Chemically Competent E. coli. [online] Available at: https://www.thermofisher.com/order/catalog/product/C404003?SID=srch-srp-C404003#/C404003?SID=srch-srp-C404003 [Accessed 7 Mar. 2020].Theilade, E., Wright, W. H., Jensen, S. B., & Löe, H. (1966). Experimental gingivitis in man. II. A longitudinal clinical and bacteriological investigation. Journal of periodontal research, 1, 1–13. https://doi.org/10.1111/j.1600-0765.1966.tb01842.xUnriza-Puin, S., Bautista-Molano, W., Lafaurie, G. I., Valle-Oñate, R., Chalem, P., Chila-Moreno, L., Bello-Gualtero, J. M., & Romero-Sánchez, C. (2017). Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives?. Clinical rheumatology, 36(4), 799–806. https://doi.org/10.1007/s10067-016-3519-zUhlig, T., Hagen, K. B., & Kvien, T. K. (1999). Current tobacco smoking, formal education, and the risk of rheumatoid arthritis. The Journal of rheumatology, 26(1), 47–54.Usui, M., Onizuka, S., Sato, T., Kokabu, S., Ariyoshi, W., & Nakashima, K. (2021). Mechanism of alveolar bone destruction in periodontitis - Periodontal bacteria and inflammation. The Japanese dental science review, 57, 201–208. https://doi.org/10.1016/j.jdsr.2021.09.005Veillard, F., Potempa, B., Guo, Y., Ksiazek, M., Sztukowska, M. N., Houston, J. A., Koneru, L., Nguyen, K. A., & Potempa, J. (2015). Purification and characterisation of recombinant His-tagged RgpB gingipain from Porphyromonas gingivalis. Biological chemistry, 396(4), 377–384. https://doi.org/10.1515/hsz-2014-0304Vermilyea, D. M., Moradali, M. F., Kim, H. M., & Davey, M. E. (2021). PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis. Journal of bacteriology, 203(4), e00343-20. https://doi.org/10.1128/JB.00343-20Vermilyea, D. M., Ottenberg, G. K., & Davey, M. E. (2019). Citrullination mediated by PPAD constrains biofilm formation in P. gingivalis strain 381. NPJ biofilms and microbiomes, 5(1), 7. https://doi.org/10.1038/s41522-019-0081-xVidal, J., Canizález-Román, A., Gutiérrez-Jiménez, J., Navarro-García, F. (2007) Patogénesis molecular, epidemiología y diagnóstico de Escherichia coli enteropatógena. Salud Pública de México. 2007;49(5), 376-386.Vossenaar, E. R., Radstake, T. R., van der Heijden, A., van Mansum, M. A., Dieteren, C., de Rooij, D. J., Barrera, P., Zendman, A. J., & van Venrooij, W. J. (2004). Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Annals of the rheumatic diseases, 63(4), 373–381. https://doi.org/10.1136/ard.2003.012211Wegner, N., Wait, R., Sroka, A., Eick, S., Nguyen, K. A., Lundberg, K., Kinloch, A., Culshaw, S., Potempa, J., & Venables, P. J. (2010). Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis and rheumatism, 62(9), 2662–2672. https://doi.org/10.1002/art.27552Wilensky, A., Polak, D., Houri-Haddad, Y., & Shapira, L. (2013). The role of RgpA in the pathogenicity of Porphyromonas gingivalis in the murine periodontitis model. Journal of Clinical Periodontology, 40(10), 924–932. https://doi.org/10.1111/jcpe.12139Wingrove, J. A., DiScipio, R. G., Chen, Z., Potempa, J., Travis, J., & Hugli, T. E. (1992). Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. The Journal of biological chemistry, 267(26), 18902–18907.Witalison, E. E., Thompson, P. R., & Hofseth, L. J. (2015). Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation. Current drug targets, 16(7), 700–710. https://doi.org/10.2174/1389450116666150202160954Wirth, R., Pap, B., Maróti, G., Vályi, P., Komlósi, L., Barta, N., Strang, O., Minárovits, J., & Kovács, K. L. (2021). Toward Personalized Oral Diagnosis: Distinct Microbiome Clusters in Periodontitis Biofilms. Frontiers in cellular and infection microbiology, 11, 747814. https://doi.org/10.3389/fcimb.2021.747814Xiao, L., Zhang, Q., Peng, Y., Wang, D., & Liu, Y. (2020). The effect of periodontal bacteria infection on incidence and prognosis of cancer: A systematic review and meta-analysis. Medicine, 99(15), e19698. https://doi.org/10.1097/MD.0000000000019698Xie H. (2015). Biogenesis and function of Porphyromonas gingivalis outer membrane vesicles. Future microbiology, 10(9), 1517–1527. https://doi.org/10.2217/fmb.15.63Xu, H., Zhao, H., Fan, D., Liu, M., Cao, J., Xia, Y., Ju, D., Xiao, C., & Guan, Q. (2020). Interactions between Gut Microbiota and Immunomodulatory Cells in Rheumatoid Arthritis. Mediators of inflammation, 2020, 1430605. https://doi.org/10.1155/2020/1430605Yamakawa, M., Ouhara, K., Kajiya, M., Munenaga, S., Kittaka, M., Yamasaki, S., Takeda, K., Takeshita, K., Mizuno, N., Fujita, T., Sugiyama, E., & Kurihara, H. (2016). Porphyromonas gingivalis infection exacerbates the onset of rheumatoid arthritis in SKG mice. Clinical and experimental immunology, 186(2), 177–189. https://doi.org/10.1111/cei.12847Yuzhalin A. E. (2019). Citrullination in Cancer. Cancer research, 79(7), 1274–1284. https://doi.org/10.1158/0008-5472.CAN-18-2797Zhou, N., Zou, F., Cheng, X., Huang, Y., Zou, H., Niu, Q., Qiu, Y., Shan, F., Luo, A., Teng, W., & Sun, J. (2021). Porphyromonas gingivalis induces periodontitis, causes immune imbalance, and promotes rheumatoid arthritis. Journal of leukocyte biology, 110(3), 461–473. https://doi.org/10.1002/JLB.3MA0121-045RZhou, X. Y., Gao, J. L., Hunter, N., Potempa, J., & Nguyen, K. A. (2013). Sequence-independent processing site of the C-terminal domain (CTD) influences maturation of the RgpB protease from Porphyromonas gingivalis. Molecular microbiology, 89(5), 903–917. https://doi.org/10.1111/mmi.12319Minciencias- Ministerio de Ciencia Tecnología e Innovación.InvestigadoresORIGINAL52882038.2022.pdf52882038.2022.pdfTesis Doctorado en Biotecnologíaapplication/pdf3282943https://repositorio.unal.edu.co/bitstream/unal/83320/2/52882038.2022.pdf41c0e5a5703d2a928fbb2f6db41ff54cMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83320/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51unal/83320oai:repositorio.unal.edu.co:unal/833202023-02-06 11:54:22.475Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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

Presencia de RgpA, anticuerpos anti-RgpA y su asociación con artritis reumatoide

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