Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea

Porphyromonas gingivalis es un anaerobio facultativo, Gram negativo con forma cocobacilar, no posee flagelos por lo que es inmóvil, es uno de los microorganismos que con mayor frecuencia se encuentra implicado en la formación de biofilm dental subgingival, por lo que se asocia principalmente con pat...

Full description

Autores:
Pinilla Torres, Laura Lizeth
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2022
Institución:
Colegio Mayor de Cundinamarca
Repositorio:
Repositorio Colegio Mayor de Cundinamarca
Idioma:
spa
OAI Identifier:
oai:repositorio.unicolmayor.edu.co:unicolmayor/5674
Acceso en línea:
https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5674
Palabra clave:
Inflamación
Bacteria
Enzima
Anticuerpos
Periodontitis
Autoinmunidad
Rights
closedAccess
License
Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2022
id UCOLMAYOR2_1346e2d5a25a0de6306e2e616debfe4b
oai_identifier_str oai:repositorio.unicolmayor.edu.co:unicolmayor/5674
network_acronym_str UCOLMAYOR2
network_name_str Repositorio Colegio Mayor de Cundinamarca
repository_id_str
dc.title.spa.fl_str_mv Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
title Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
spellingShingle Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
Inflamación
Bacteria
Enzima
Anticuerpos
Periodontitis
Autoinmunidad
title_short Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
title_full Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
title_fullStr Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
title_full_unstemmed Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
title_sort Revisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis Reumatoidea
dc.creator.fl_str_mv Pinilla Torres, Laura Lizeth
dc.contributor.advisor.none.fl_str_mv Castro Molina, Susan Lorena
dc.contributor.author.none.fl_str_mv Pinilla Torres, Laura Lizeth
dc.subject.lemb.none.fl_str_mv Inflamación
Bacteria
Enzima
topic Inflamación
Bacteria
Enzima
Anticuerpos
Periodontitis
Autoinmunidad
dc.subject.proposal.spa.fl_str_mv Anticuerpos
Periodontitis
Autoinmunidad
description Porphyromonas gingivalis es un anaerobio facultativo, Gram negativo con forma cocobacilar, no posee flagelos por lo que es inmóvil, es uno de los microorganismos que con mayor frecuencia se encuentra implicado en la formación de biofilm dental subgingival, por lo que se asocia principalmente con patologías orales como la periodontitis, esta se caracteriza por producir inflamación gingival, produciendo en los casos más graves, degradación de las encías y pérdida ósea. Uno de los factores de virulencia que se encuentran implicados en el desarrollo crónico de la periodontitis es la presencia de la enzima peptidil arginina deaminasa (PPDA), la cual se considera como homóloga a la peptidil arginina deaminasa humana (PAD), implicada en el desarrollo de anticuerpos anti péptido citrulinado cíclico ( Anti - CCP), estos se desarrollan gracias a la catálisis de la arginina en citrulina por medio de esta enzima lo que conlleva a un cambio postransduccional dando como resultado dicha modificación, esto se produce gracias a la activación de la enzima al haber altos niveles de calcio intracelular cuando hay apoptosis o daño celular como en el caso de la artritis reumatoide (AR) por lo que estos anticuerpos se han usado como diagnóstico y pronóstico de esta enfermedad. En la presente revisión se explicarán las posibles formas en las que la enzima PPDA y P. gingivalis son capaces de producir Anti CCP y relacionarse con la AR.
publishDate 2022
dc.date.accessioned.none.fl_str_mv 2022-10-03T16:36:46Z
dc.date.available.none.fl_str_mv 2022-10-03T16:36:46Z
dc.date.issued.none.fl_str_mv 2022
dc.type.spa.fl_str_mv Trabajo de grado - Pregrado
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.content.spa.fl_str_mv Text
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/bachelorThesis
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/TP
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_7a1f
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5674
url https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5674
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv 1. Ramos D, Moromi H, Martínez E. Porphyromonas gingivalis: patógeno predominante en la periodontitis crónica. Odontol. Sanmarquina [Internet] 2011 [Citado 2021 23 Sep]; 14(1): 34- 38 Disponible en: https://sisbib.unmsm.edu.pe/bvrevistas/odontologia/2011_n1/pdf/a11.pdf
Reyes L. Porphyromonas gingivalis. Trends in Micriobiology. [Internet] 2021 Apr [Cited 2021 23 Sep]; 29(4): 376-377
Jia L, Han N, Du J, Guo L, Luo Z, Liu Y. Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors. Front Biosci. [Internet] 2019 Jul [Cited 2022 20 Feb]; 9:262 Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657652/
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature [Internet]. 2003 May 15 [cited 2019 Apr 9];423(6937):356–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12748655
Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L. Immunity to Citrullinated Proteins in Rheumatoid Arthritis. Annu Rev Immunol [Internet]. 2008 Apr [cited 2019 Apr 10];26(1):651–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18173373
Wegner N, Lundberg K, Kinloch A, Fisher B, Malmström V, Feldmann M, et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. [Internet]. 2010 [cited 2019 Apr 10]; 233(1):34–54. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0105- 2896.2009.00850.x
Feng L, Zubing L, Yining W, Bin S, Zhongcheng G, Xiangrong C. Porphyromonas gingivalis may play an important role on the pathogenesis of periodontitis-associated rheumatoid arthritis. Medical Hypotheses [Internet] 2009 [Citado 2021 Sep 15]; 72 (6): 732- 735 Available in: https://www.sciencedirect.com/science/article/abs/pii/S0306987709000504?via%3Dihubscien cedir%20ect.com/science/article/abs/pii/S0306987709000504?via%3Dihub
Facultad de odontología sede Bogotá. Guía de Atención en Periodoncia. Universidad Nacional. [Internet] 2013 [Citado 2020 Sep 21]. Disponible en: http://www.odontologia.unal.edu.co/docs/habilitacion/guia_atencion_periodoncia_abril _2013.pdf
Diaz, A. Efecto de Porphyromonas gingivalis en la Activación y Adhesión de Plaquetas Humanas en Co-cultivo con Células Endoteliales de Arteria Coronaria Humana. Universidad del Bosque [Internet] 2018 Nov [Cited 2022 20 Mar]; 333 (1): 1-9 Avilable in: https://repositorio.unbosque.edu.co/bitstream/handle/20.500.12495/2202/Díaz_Real_María_Al ejandra_2018.pdf?sequence=1&isAllowed=y
Mikuls TR, Payne JB, Yu F, Thiele GM, Reynolds RJ, Cannon GW, et al. Periodontitis and Porphyromonas gingivalis in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2014 May;66(5):1090–100. https://pubmed.ncbi.nlm.nih.gov/24782175/
Shaun M, Antonette G, Rachelle M, Carlos A, Hansel M, Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis. Front Biosci. [Internet] 2008 May [Cited 2022 10 Feb]; 13 (32): 15-38. Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403687/
Lunar I, Cascales E. Molecular Strategies Underlying Porphyromonas gingivalis Virulence. JMB. [Internet] 2021 Apr [Cited 2021 23 Sep]; 433(7)
Mercado F, Marshall RI, Klestov AC, Bartold PM. Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol. 2000 Apr;27(4):267–72. https://pubmed.ncbi.nlm.nih.gov/10783841/
Carvajal Paola. Enfermedades periodontales como un problema de salud pública: el desafío del nivel primario de atención en salud. Rev. Clin. Periodoncia Implantol. Rehabil. Oral [Internet]. 2016 Ago [citado 2022 Mar 15] ; 9( 2 ): 177-183. Disponible en: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0719-01072016000200016&lng=es
Botoreo J, Bedoya E. Determinantes del Diagnóstico Periodontal. Rev. Clin. Periodoncia Implantol. Rehabil. Oral. [Internet] 2010 [Citado 2020 Sep 18]; 3(2); 94- 99. Disponible en: https://scielo.conicyt.cl/pdf/piro/v3n2/art07.pdf
Nagpal R, Yamashiro Y, Izumi Y. The Two-Way Association of Periodontal Infection with Systemic Disorders: An Overview. Mediators Inflamm. 2015;2015:1–9. https://pubmed.ncbi.nlm.nih.gov/26339142/
Burska AN, Hunt L, Boissinot M, Strollo R, Ryan BJ, Vital E, et al. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis. Mediators Inflamm. [Internet] 2014 [cited 2019 May 28]; 2014:1–19. Available from: https://pubmed.ncbi.nlm.nih.gov/24782594/
Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, et al. The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol. [Internet] 1999 Jan [cited 2020 Jul 30];162(1):585–94. Available from: https://pubmed.ncbi.nlm.nih.gov/9886436/
Anderton SM. Post-translational modifications of self antigens: implications for autoimmunity. Curr Opin Immunol. [Internet] 2004 Dec [cited 2019 29 May];16(6):753– 8. Available from: https://pubmed.ncbi.nlm.nih.gov/15511669/
Quirke A-M, Fisher BAC, Kinloch AJ, Venables PJ. Citrullination of autoantigens: Upstream of TNFα in the pathogenesis of rheumatoid arthritis. FEBS Lett. [Internet] 2011 Dec [cited 2020 Aug 18];585(23):3681–8. Available from: https://pubmed.ncbi.nlm.nih.gov/21704035/
Sebbag M, Moinard N, Auger I, Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins. Eur J Immunol. [Internet] 2006 Aug [cited 2020 Aug 13];36(8):2250–63. Available from: https://pubmed.ncbi.nlm.nih.gov/16838278/
Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. [Internet] 2012 Dec [cited 2019 Mar 25];18(13 Suppl):S295-302. Available from: https://pubmed.ncbi.nlm.nih.gov/23327517/
Nissim A, Winyard PG, Corrigall V, Fatah R, Perrett D, Panayi G, et al. Generation of neoantigenic epitopes after posttranslational modification of type II collagen by factors present within the inflamed joint. Arthritis Rheum. [Internet] 2005 Dec [cited 2019 May 3];52(12):3829–38. Available from: https://pubmed.ncbi.nlm.nih.gov/16329077/
Bright R, Proudman SM, Rosenstein ED, Bartold PM. Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis? Med Hypotheses [Internet]. 2015 Jun [cited 2020 Jul 27];84(6):570–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0306987715001115
Aggarwal R, Liao K, Nair R, Ringold S, Costenbander KH. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Arthritis Care Res (Hoboken). [Internet] 2009 Nov [cited 2020 Jul 25];61(11):1472–83. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859449/pdf/nihms 178426.pdf
Sebbag M, Chapuy-Regaud S, Auger I, Petit-Texeira E, Clavel C, Nogueira L, et al. Clinical and pathophysiological significance of the autoimmune response to citrullinated proteins in rheumatoid arthritis. Jt Bone Spine. [Internet] 2004 Nov [cited 2020 Aug 5];71(6):493–502. Available from: https://www.sciencedirect.com/science/article/pii/S1297319X04001460
Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Méchin M C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD 3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. [Internet] 2007 Nov [cited 2020 Aug 10];56(11):3541–53. Available from: https://pubmed.ncbi.nlm.nih.gov/17968929/
Correa P, Tobón G, Citera G, Cadena J, Schneeberger E, Camargo J, Et al. Anticuerpos anti-CCP en artritis reumatoidea: relación con características clínicas, citocinas Th1/Th2 y HLA-DRB1. Biomédica [Internet] 2004 [Consultado 9 de septiembre de 2020]; 24:140-152 Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/1260 68.
Casillas F, Bonilla D, Murillo J, Corona E, Contreras M, Saucedo M, Et al. Anticuerpos antipéptido citrulinado cíclico (anti-CCP) en artritis reumatoide. El Residente [Internet] 2015 [Consultado 9 de septiembre de 2020]; 10(1): 12-17. Disponible en: https://www.medigraphic.com/pdfs/residente/rr-2015/rr151c.pdf
Balsa A, Pascual D, Martín J. Anticuerpos anticitrulina en la artritis reumatoide. Med Clin [Internet] 2007 [Consultado 9 de septiembre de 2020]; 128(17):668-673. Disponible en: https://www.elsevier.es/es-revista-medicina-clinica-2-articulo anticuerpos-anticitrulina- artritis-reumatoide-13102061
Liao F, Li Z, Wang Y, Shi B, Gong Z, Cheng X. Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated rheumatoid arthritis. Med Hypotheses.[Internet] 2009 Jun [cited 2020 Aug 25];72(6):732–5. Available from: https://www.researchgate.net/publication/24043414_Porphyromonas_gingivalis_may_ play_an_important_role_in_the_pathogenesis_of_periodontitis associated_rheumatoid_arthritis
Del Río P. ACTIVIDAD BIOCIDA DE UN PROPOLIS CHILENO FRENTE A Porphyromonas gingivalis: ESTUDIO in vitro. Universdad de Chile [Internet] 2006 [Citado 2021 23 Sep]; 20-26 Disponible en: http://www.tesis.uchile.cl/tesis/uchile/2006/delrio_p/sources/delrio_p.pdf
Baka Z, György B, Géher P, Buzás EI, Falus A, Nagy G. Citrullination under physiological and pathological conditions. Jt Bone Spine. [Internet] 2012 Oct [cited 2019 Jun 20];79(5):431–6. Available from: https://pubmed.ncbi.nlm.nih.gov/22366145/(7)
Xu W, Zhou W, Wang H, Liang S. Chapter Two - Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Advances in Protein Chemistry and Structural Biology. [Internet] 2020 [Cited 2021 23 Sep]; 120: 45-84
Bascones A, Figuero E. Las enfermedades periodontales como infecciones bacterianas. Med Oral Patol Oral Cir Bucal. [Internet] 2005 [citado 2020 Sep 20]; 17(3): 92-107. Disponible en: http://scielo.isciii.es/pdf/peri/v17n3/147enfermedades.pdf
Gómez A. Anticuerpos anti-PCC. Rev. Española de Reumatología. [Internet] 2005 [Consultado 9 de septiembre de 2020]. 32(3): 85-87. Disponible en: https://www.elsevier.es/es-revista-revista-espanola-reumatologia-29-articulo anticuerpos-anti- pcc-13073663
Gutiérrez E, Martínez M,Zapata M, Sánchez S. Artritis Reumatoide: Prevalencia, inmunopatogenia y antígenos relevantes para su diagnóstico. MedPub [Internet] 2012 [Consultado 9 de septiembre de 2020]; 8(1):3. Disponible en: https://www.archivosdemedicina.com/medicina-de-familia/artritis- reumatoideprevalencia-inmunopatogenia-y-antgenos-relevantes-para-su- diagnstio.pdf
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. [Internet] 2010 [cited 2020 Aug 3];62(9):2569–81. Available from: https://pubmed.ncbi.nlm.nih.gov/20872595/
Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, et al. The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the - and -Chains of Fibrin. J Immunol. 2001 Mar;166(6):4177–84.
Bang H, Egerer K, Gauliard A, Lüthke K, Rudolph PE, Fredenhagen G, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007 Aug;56(8):2503–11.
Kinloch A, Tatzer V, Wait R, Peston D, Lundberg K, Donatien P, et al. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res Ther. 2005;7(6):R1421-9.
Jones V, Taylor PC, Jacoby RK, Wallington TB. Synovial synthesis of rheumatoid factors and immune complex constituents in early arthritis. Ann Rheum Dis. 1984 Apr;43(2):235–9
Quirke A-M, Fisher BAC, Kinloch AJ, Venables PJ. Citrullination of autoantigens: Upstream of TNFα in the pathogenesis of rheumatoid arthritis. FEBS Lett. [Internet] 2011 Dec [cited 2020 Aug 18];585(23):3681–8. Available from: https://pubmed.ncbi.nlm.nih.gov/21704035/
Vander Cruyssen B, Cantaert T, Nogueira L, Clavel C, De Rycke L, Dendoven A, et al. Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays. Arthritis Res Ther. [Internet] 2006 [cited 2020 Aug 20];8(4):R122. Available form: https://pubmed.ncbi.nlm.nih.gov/16859515/
Chapuy-Regaud S, Nogueira L, Clavel C, Sebbag M, Vincent C, Serre G. IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin. Clin Exp Immunol. [Internet] 2005 Mar[cited 2020 Aug 23];139(3):542–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18093
McInnes IB, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med [Internet]. 2011 Dec 8 [cited 2019 Mar 15];365(23):2205–19. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMra1004965
Marcinkiewicz J, Biedroń R, Maresz K, Kwaśny-Krochin B, Bobek M, Kontny E, et al. Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis. Arch Immunol Ther Exp (Warsz). 52(4):284– 91. https://pubmed.ncbi.nlm.nih.gov/15467493/
Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GMC, van Veelen P a., et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci. [Internet] 2011 [cited 2019 Jun 8];108(42):17372–7. Available from: https://pubmed.ncbi.nlm.nih.gov/21987802/
Eggleton P, Nissim A, Ryan BJ, Whiteman M, Winyard PG. Detection and isolation of human serum autoantibodies that recognize oxidatively modified autoantigens. Free Radic Biol Med. [internet] 2013 Apr [cited 2019 Jun 10];57:79–91. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0891584912018060
Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK. Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine. J Lipid Res. 1984 Oct;25(10):1109–16.
Valesini G, Gerardi MC, Iannuccelli C, Pacucci VA, Pendolino M, Shoenfeld Y. Citrullination and autoimmunity. Autoimmun Rev. [Internet] 2015 Jun [cited 2019 Jun 15];14(6):490–7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1568997215000282
Bax M, van Heemst J, Huizinga TWJ, Toes REM. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics. 2011 Aug;63(8):459–66. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132380/
O’Dell J. Rheumatoid arthritis. In: Goldman L, Schafer AI E, editor. Goldman’s Cecil Medicine. 25th ed. Philadelphia: Elsevier Saunders; 2016.
Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum [Internet]. 1987 Nov [cited 2019 Apr 9];30(11):1205–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2446635
Nell VPK. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005 Dec;64(12):1731
Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis. 2001 Mar;60(3):223–7. Available from: https://pubmed.ncbi.nlm.nih.gov/11171682/
Källberg H, Ding B, Padyukov L, Bengtsson C, Rönnelid J, Klareskog L, et al. Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis. 2011 Mar;70(3):508–11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033966/pdf/nihms 263734.pdf
Karlson EW, Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum. 1999 May;42(5):910–7. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1002/1529- 0131%28199905%2942%3A5%3C910%3A%3AAID-ANR9%3E3.0.CO%3B2-D
Klareskog L, Malmström V, Lundberg K, Padyukov L, Alfredsson L. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Semin Immunol. 2011 Apr;23(2):92–8.
Klareskog L, Stolt P, Lundberg K, Källberg H, Bengtsson C, Grunewald J, et al. A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006 Jan;54(1):38–46.
Makrygiannakis D, Hermansson M, Ulfgren A-K, Nicholas AP, Zendman AJW, Eklund A, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis. 2008 Oct;67(10):1488–92.
Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004 Oct;50(10):3085–92.
Linn-Rasker SP. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006 Mar;65(3):366–71.
Pedersen M, Jacobsen S, Garred P, Madsen HO, Klarlund M, Svejgaard A, et al. Strong combined gene–environment effects in anti–cyclic citrullinated peptide– positive rheumatoid arthritis: A nationwide case–control study in Denmark. Arthritis Rheum. 2007 May;56(5):1446–53.
Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L. Gene environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: All alleles are important. Arthritis Rheum. 2009 Jun;60(6):1597–603.
Wernick RM, Lipsky PE, Marban-Arcos E, Maliakkal JJ, Edelbaum D, Ziff M. IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures. Arthritis Rheum. 1985 Jul;28(7):742–52.
Mysak J, Podzimek S, Sommerova P, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. [Internet] 2014 Mar [Cited 2022 25 Feb]; 2014 (47) 60-68. Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984870/#
Bostanci N, Belibasakis G. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiology Letters [Internet] 2012 Aug [Cited 2022 20 Mar]; 333 (1): 1-9 Avilable in: https://academic.oup.com/femsle/article/333/1/1/586464?login=false
Koziel J, Mydel P, Potempa J. The Link Between Periodontal Disease and Rheumatoid Arthritis: An Updated Review. Curr Rheumatol Rep. [Internet] 2014 Jan [Cited 2022 26 Mar]; 16(3): 408 Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930831/
Lamont RJ, Jenkinson HF. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev. 1998 Dec;62(4):1244–63.
Manga P, Wegner N, Venables PJ, Potempa J. Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis? Arthritis Res Ther. 2010;12(3):209.
Koziel J, Mydel P, Potempa J. The link between periodontal disease and rheumatoid arthritis: an updated review. Curr Rheumatol Rep. 2014 Mar;16(3):408.
Socransky SS, Haffajee AD. Effect of Therapy on Periodontal Infections. J Periodontol. 1993 Aug;64(8s):754–9.
Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonas gingivalis. Periodontol 2000. 1999 Jun;20:168–238.
Kesavalu L, Holt SC, Ebersole JL. Trypsin-like protease activity of Porphyromonas gingivalis as a potential virulence factor in a murine lesion model. Microb Pathog. 1996 Jan;20(1):1–10.
Birkedal-Hansen H, Taylor RE, Zambon JJ, Barwa PK, Neiders ME. Characterization of collagenolytic activity from strains of Bacteroides gingivalis. J Periodontal Res. 1988 Jul;23(4):258–64.
McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun. 1999 Jul;67(7):3248–56.
Wegner N, Wait R, Sroka A, Eick S, Nguyen K-A, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: Implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum [Internet]. 2010 Sep [cited 2019 Jul 29];62(9):2662–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20506214
Batool H, Afzal N, Shahzad F, Kashif M. Relationship between rheumatoid arthritis and chronic periodontitis. J Med Radiol Pathol Surg. 2016;2(6):11–4.
Rodríguez SB, Stitt BL, Ash DE. Cysteine 351 is an essential nucleophile in catalysis by Porphyromonas gingivalis peptidylarginine deiminase. Arch Biochem Biophys. 2010 Dec;504(2):190–6.
Farquharson D, Butcher JP, Culshaw S. Periodontitis, Porphyromonas, and the pathogenesis of rheumatoid arthritis. Mucosal Immunol [Internet]. 2012;5(2):112– 20. Available from: http://dx.doi.org/10.1038/mi.2011.66
Brinkmann V. Neutrophil Extracellular Traps Kill Bacteria. Science (80- ). 2004 Mar;303(5663):1532–5.
Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol. 2007 Aug;5(8):577–82.
Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008 Feb;180(3):1895–902.
Liubomorova I. State of periodontium in patients affected with rheumatism. Stomatologiia (Mosk). 1964;33 – 37.
Mercado FB, Marshall RI, Klestov AC, Bartold PM. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001 Jun;72(6):779–87.
Arkema E V., Karlson EW, Costenbader KH. A Prospective Study of Periodontal Disease and Risk of Rheumatoid Arthritis. J Rheumatol. 2010 Sep;37(9):1800–4.
Abdelsalam SK, Hashim NT, Elsalamabi EM, Gismalla BG. Periodontal status of rheumatoid arthritis patients in khartoum state. BMC Res Notes. 2011;4(1):460.
89. Gleissner C, Willershausen B, Kaesser U, Bolten WW. The role of risk factors for periodontal disease in patients with rheumatoid arthritis. Eur J Med Res. 1998 Aug;3(8):387–92.
90. Kässer UR, Gleissner C, Dehne F, Michel A, Willershausen-Zönnchen B, Bolten WW. Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum. 1997 Dec;40(12):2248–51.
91. Cooles FAH, Isaacs JD. Pathophysiology of rheumatoid arthritis. Curr Opin Rheumatol. 2011 May;23(3):233–40.
dc.rights.eng.fl_str_mv Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2022
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/closedAccess
dc.rights.creativecommons.spa.fl_str_mv Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_14cb
rights_invalid_str_mv Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2022
https://creativecommons.org/licenses/by-nc-sa/4.0/
Atribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)
http://purl.org/coar/access_right/c_14cb
eu_rights_str_mv closedAccess
dc.format.extent.spa.fl_str_mv 57p.
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias de la Salud
dc.publisher.place.spa.fl_str_mv Bogotá
dc.publisher.program.spa.fl_str_mv Bacteriología y Laboratorio Clínico
institution Colegio Mayor de Cundinamarca
bitstream.url.fl_str_mv https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/1/Pinilla%20Torres%20Laura%20Lizeth.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/2/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/3/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/4/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdf
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/5/license.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/6/Pinilla%20Torres%20Laura%20Lizeth.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/8/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/10/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/12/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdf.txt
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/7/Pinilla%20Torres%20Laura%20Lizeth.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/9/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/11/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf.jpg
https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/13/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdf.jpg
bitstream.checksum.fl_str_mv 41d1af1b8f6ab5fa93919f573d160295
16dcb80aa80672da00c9794b435ec286
2353f0e3f87651c3086cebcdd1ded829
e24a90df09b81a51c81795fadd4b6a85
2f9959eaf5b71fae44bbf9ec84150c7a
e9b2325950e37c260e781b914cabedb0
c82b8b4119f274a4d8ceae29472e5222
74f16f331746e8c35008f5d57de37c04
aeaad6a1c45cbdba719b87bbd40e9c32
f1a0710d4dfcb45d5a2f3a7239411bbd
a80819607e4c73b2842ddcd9d4db0095
79ade22e04f4e186a5c1a3c42d94dcbd
64054b136184a739c9f8e3d06149b2ea
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital Unicolmayor
repository.mail.fl_str_mv repositorio@unicolmayor.edu.co
_version_ 1812210070437494784
spelling Castro Molina, Susan Lorena0538d7d5bb55e1323777cf3c55bf6d1a600Pinilla Torres, Laura Lizeth2e8f7fc4b7f6a905cd6cacd21033c5d56002022-10-03T16:36:46Z2022-10-03T16:36:46Z2022https://repositorio.unicolmayor.edu.co/handle/unicolmayor/5674Porphyromonas gingivalis es un anaerobio facultativo, Gram negativo con forma cocobacilar, no posee flagelos por lo que es inmóvil, es uno de los microorganismos que con mayor frecuencia se encuentra implicado en la formación de biofilm dental subgingival, por lo que se asocia principalmente con patologías orales como la periodontitis, esta se caracteriza por producir inflamación gingival, produciendo en los casos más graves, degradación de las encías y pérdida ósea. Uno de los factores de virulencia que se encuentran implicados en el desarrollo crónico de la periodontitis es la presencia de la enzima peptidil arginina deaminasa (PPDA), la cual se considera como homóloga a la peptidil arginina deaminasa humana (PAD), implicada en el desarrollo de anticuerpos anti péptido citrulinado cíclico ( Anti - CCP), estos se desarrollan gracias a la catálisis de la arginina en citrulina por medio de esta enzima lo que conlleva a un cambio postransduccional dando como resultado dicha modificación, esto se produce gracias a la activación de la enzima al haber altos niveles de calcio intracelular cuando hay apoptosis o daño celular como en el caso de la artritis reumatoide (AR) por lo que estos anticuerpos se han usado como diagnóstico y pronóstico de esta enfermedad. En la presente revisión se explicarán las posibles formas en las que la enzima PPDA y P. gingivalis son capaces de producir Anti CCP y relacionarse con la AR.TABLA DE CONTENIDO RESUMEN.7 INTRODUCCIÓN..8 1. Planteamiento del problema...9 2. Objetivos ....10 2.1 Objetivo General 10 2.3 Objetivos Específicos10 3. Justificación ......11 4. Antecedentes.....11 5. Marco Teórico ..22 5.1 Porhyromonas gingivalis:...22 5.1.1 Factores de Virulencia .23 5.2 Enfermedad periodontal: ...24 5.3 Anticuerpos Anti-Proteínas Citrulinadas (ANTI-CCP). 25 5.4 Artritis Reumatoide .27 5.4.1 Factores de Riesgo.29 6. Diseño metodológico...31 6.1 Tipo de investigación: .....31 6.2 Alcance de la investigación.31 6.3 Población..32 6.4 Muestra ....32 6.5 Variables ..32 6.5.1 Variable dependiente ...32 6.5.2 Variable independiente 32 7. Metodología ......33 7.1 Revisión bibliográfica .....33 7.2 Selección de material bibliográfico.33 8. Resultados..34 9. Discusión ....41 10. Conclusiones ...45 11. Referencias.....46PregradoBacteriólogo(a) y Laboratorista Clínico57p.application/pdfspaDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2022https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbRevisión documental de la relación de porphyromonas GINGIVALIS y los Anticuerpos anti-péptido citrulinado cíclico en la artritis ReumatoideaTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionFacultad de Ciencias de la SaludBogotáBacteriología y Laboratorio Clínico1. Ramos D, Moromi H, Martínez E. Porphyromonas gingivalis: patógeno predominante en la periodontitis crónica. Odontol. Sanmarquina [Internet] 2011 [Citado 2021 23 Sep]; 14(1): 34- 38 Disponible en: https://sisbib.unmsm.edu.pe/bvrevistas/odontologia/2011_n1/pdf/a11.pdfReyes L. Porphyromonas gingivalis. Trends in Micriobiology. [Internet] 2021 Apr [Cited 2021 23 Sep]; 29(4): 376-377Jia L, Han N, Du J, Guo L, Luo Z, Liu Y. Pathogenesis of Important Virulence Factors of Porphyromonas gingivalis via Toll-Like Receptors. Front Biosci. [Internet] 2019 Jul [Cited 2022 20 Feb]; 9:262 Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657652/Firestein GS. Evolving concepts of rheumatoid arthritis. Nature [Internet]. 2003 May 15 [cited 2019 Apr 9];423(6937):356–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12748655Klareskog L, Rönnelid J, Lundberg K, Padyukov L, Alfredsson L. Immunity to Citrullinated Proteins in Rheumatoid Arthritis. Annu Rev Immunol [Internet]. 2008 Apr [cited 2019 Apr 10];26(1):651–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18173373Wegner N, Lundberg K, Kinloch A, Fisher B, Malmström V, Feldmann M, et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. [Internet]. 2010 [cited 2019 Apr 10]; 233(1):34–54. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0105- 2896.2009.00850.xFeng L, Zubing L, Yining W, Bin S, Zhongcheng G, Xiangrong C. Porphyromonas gingivalis may play an important role on the pathogenesis of periodontitis-associated rheumatoid arthritis. Medical Hypotheses [Internet] 2009 [Citado 2021 Sep 15]; 72 (6): 732- 735 Available in: https://www.sciencedirect.com/science/article/abs/pii/S0306987709000504?via%3Dihubscien cedir%20ect.com/science/article/abs/pii/S0306987709000504?via%3DihubFacultad de odontología sede Bogotá. Guía de Atención en Periodoncia. Universidad Nacional. [Internet] 2013 [Citado 2020 Sep 21]. Disponible en: http://www.odontologia.unal.edu.co/docs/habilitacion/guia_atencion_periodoncia_abril _2013.pdfDiaz, A. Efecto de Porphyromonas gingivalis en la Activación y Adhesión de Plaquetas Humanas en Co-cultivo con Células Endoteliales de Arteria Coronaria Humana. Universidad del Bosque [Internet] 2018 Nov [Cited 2022 20 Mar]; 333 (1): 1-9 Avilable in: https://repositorio.unbosque.edu.co/bitstream/handle/20.500.12495/2202/Díaz_Real_María_Al ejandra_2018.pdf?sequence=1&isAllowed=yMikuls TR, Payne JB, Yu F, Thiele GM, Reynolds RJ, Cannon GW, et al. Periodontitis and Porphyromonas gingivalis in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2014 May;66(5):1090–100. https://pubmed.ncbi.nlm.nih.gov/24782175/Shaun M, Antonette G, Rachelle M, Carlos A, Hansel M, Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis. Front Biosci. [Internet] 2008 May [Cited 2022 10 Feb]; 13 (32): 15-38. Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3403687/Lunar I, Cascales E. Molecular Strategies Underlying Porphyromonas gingivalis Virulence. JMB. [Internet] 2021 Apr [Cited 2021 23 Sep]; 433(7)Mercado F, Marshall RI, Klestov AC, Bartold PM. Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol. 2000 Apr;27(4):267–72. https://pubmed.ncbi.nlm.nih.gov/10783841/Carvajal Paola. Enfermedades periodontales como un problema de salud pública: el desafío del nivel primario de atención en salud. Rev. Clin. Periodoncia Implantol. Rehabil. Oral [Internet]. 2016 Ago [citado 2022 Mar 15] ; 9( 2 ): 177-183. Disponible en: http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0719-01072016000200016&lng=esBotoreo J, Bedoya E. Determinantes del Diagnóstico Periodontal. Rev. Clin. Periodoncia Implantol. Rehabil. Oral. [Internet] 2010 [Citado 2020 Sep 18]; 3(2); 94- 99. Disponible en: https://scielo.conicyt.cl/pdf/piro/v3n2/art07.pdfNagpal R, Yamashiro Y, Izumi Y. The Two-Way Association of Periodontal Infection with Systemic Disorders: An Overview. Mediators Inflamm. 2015;2015:1–9. https://pubmed.ncbi.nlm.nih.gov/26339142/Burska AN, Hunt L, Boissinot M, Strollo R, Ryan BJ, Vital E, et al. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis. Mediators Inflamm. [Internet] 2014 [cited 2019 May 28]; 2014:1–19. Available from: https://pubmed.ncbi.nlm.nih.gov/24782594/Girbal-Neuhauser E, Durieux JJ, Arnaud M, Dalbon P, Sebbag M, Vincent C, et al. The epitopes targeted by the rheumatoid arthritis-associated antifilaggrin autoantibodies are posttranslationally generated on various sites of (pro)filaggrin by deimination of arginine residues. J Immunol. [Internet] 1999 Jan [cited 2020 Jul 30];162(1):585–94. Available from: https://pubmed.ncbi.nlm.nih.gov/9886436/Anderton SM. Post-translational modifications of self antigens: implications for autoimmunity. Curr Opin Immunol. [Internet] 2004 Dec [cited 2019 29 May];16(6):753– 8. Available from: https://pubmed.ncbi.nlm.nih.gov/15511669/Quirke A-M, Fisher BAC, Kinloch AJ, Venables PJ. Citrullination of autoantigens: Upstream of TNFα in the pathogenesis of rheumatoid arthritis. FEBS Lett. [Internet] 2011 Dec [cited 2020 Aug 18];585(23):3681–8. Available from: https://pubmed.ncbi.nlm.nih.gov/21704035/Sebbag M, Moinard N, Auger I, Clavel C, Arnaud J, Nogueira L, et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins. Eur J Immunol. [Internet] 2006 Aug [cited 2020 Aug 13];36(8):2250–63. Available from: https://pubmed.ncbi.nlm.nih.gov/16838278/Gibofsky A. Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. Am J Manag Care. [Internet] 2012 Dec [cited 2019 Mar 25];18(13 Suppl):S295-302. Available from: https://pubmed.ncbi.nlm.nih.gov/23327517/Nissim A, Winyard PG, Corrigall V, Fatah R, Perrett D, Panayi G, et al. Generation of neoantigenic epitopes after posttranslational modification of type II collagen by factors present within the inflamed joint. Arthritis Rheum. [Internet] 2005 Dec [cited 2019 May 3];52(12):3829–38. Available from: https://pubmed.ncbi.nlm.nih.gov/16329077/Bright R, Proudman SM, Rosenstein ED, Bartold PM. Is there a link between carbamylation and citrullination in periodontal disease and rheumatoid arthritis? Med Hypotheses [Internet]. 2015 Jun [cited 2020 Jul 27];84(6):570–6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0306987715001115Aggarwal R, Liao K, Nair R, Ringold S, Costenbander KH. Anti-citrullinated peptide antibody assays and their role in the diagnosis of rheumatoid arthritis. Arthritis Care Res (Hoboken). [Internet] 2009 Nov [cited 2020 Jul 25];61(11):1472–83. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2859449/pdf/nihms 178426.pdfSebbag M, Chapuy-Regaud S, Auger I, Petit-Texeira E, Clavel C, Nogueira L, et al. Clinical and pathophysiological significance of the autoimmune response to citrullinated proteins in rheumatoid arthritis. Jt Bone Spine. [Internet] 2004 Nov [cited 2020 Aug 5];71(6):493–502. Available from: https://www.sciencedirect.com/science/article/pii/S1297319X04001460Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Méchin M C, et al. Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD 3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. [Internet] 2007 Nov [cited 2020 Aug 10];56(11):3541–53. Available from: https://pubmed.ncbi.nlm.nih.gov/17968929/Correa P, Tobón G, Citera G, Cadena J, Schneeberger E, Camargo J, Et al. Anticuerpos anti-CCP en artritis reumatoidea: relación con características clínicas, citocinas Th1/Th2 y HLA-DRB1. Biomédica [Internet] 2004 [Consultado 9 de septiembre de 2020]; 24:140-152 Disponible en: https://revistabiomedica.org/index.php/biomedica/article/view/1260 68.Casillas F, Bonilla D, Murillo J, Corona E, Contreras M, Saucedo M, Et al. Anticuerpos antipéptido citrulinado cíclico (anti-CCP) en artritis reumatoide. El Residente [Internet] 2015 [Consultado 9 de septiembre de 2020]; 10(1): 12-17. Disponible en: https://www.medigraphic.com/pdfs/residente/rr-2015/rr151c.pdfBalsa A, Pascual D, Martín J. Anticuerpos anticitrulina en la artritis reumatoide. Med Clin [Internet] 2007 [Consultado 9 de septiembre de 2020]; 128(17):668-673. Disponible en: https://www.elsevier.es/es-revista-medicina-clinica-2-articulo anticuerpos-anticitrulina- artritis-reumatoide-13102061Liao F, Li Z, Wang Y, Shi B, Gong Z, Cheng X. Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated rheumatoid arthritis. Med Hypotheses.[Internet] 2009 Jun [cited 2020 Aug 25];72(6):732–5. Available from: https://www.researchgate.net/publication/24043414_Porphyromonas_gingivalis_may_ play_an_important_role_in_the_pathogenesis_of_periodontitis associated_rheumatoid_arthritisDel Río P. ACTIVIDAD BIOCIDA DE UN PROPOLIS CHILENO FRENTE A Porphyromonas gingivalis: ESTUDIO in vitro. Universdad de Chile [Internet] 2006 [Citado 2021 23 Sep]; 20-26 Disponible en: http://www.tesis.uchile.cl/tesis/uchile/2006/delrio_p/sources/delrio_p.pdfBaka Z, György B, Géher P, Buzás EI, Falus A, Nagy G. Citrullination under physiological and pathological conditions. Jt Bone Spine. [Internet] 2012 Oct [cited 2019 Jun 20];79(5):431–6. Available from: https://pubmed.ncbi.nlm.nih.gov/22366145/(7)Xu W, Zhou W, Wang H, Liang S. Chapter Two - Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Advances in Protein Chemistry and Structural Biology. [Internet] 2020 [Cited 2021 23 Sep]; 120: 45-84Bascones A, Figuero E. Las enfermedades periodontales como infecciones bacterianas. Med Oral Patol Oral Cir Bucal. [Internet] 2005 [citado 2020 Sep 20]; 17(3): 92-107. Disponible en: http://scielo.isciii.es/pdf/peri/v17n3/147enfermedades.pdfGómez A. Anticuerpos anti-PCC. Rev. Española de Reumatología. [Internet] 2005 [Consultado 9 de septiembre de 2020]. 32(3): 85-87. Disponible en: https://www.elsevier.es/es-revista-revista-espanola-reumatologia-29-articulo anticuerpos-anti- pcc-13073663Gutiérrez E, Martínez M,Zapata M, Sánchez S. Artritis Reumatoide: Prevalencia, inmunopatogenia y antígenos relevantes para su diagnóstico. MedPub [Internet] 2012 [Consultado 9 de septiembre de 2020]; 8(1):3. Disponible en: https://www.archivosdemedicina.com/medicina-de-familia/artritis- reumatoideprevalencia-inmunopatogenia-y-antgenos-relevantes-para-su- diagnstio.pdfAletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. [Internet] 2010 [cited 2020 Aug 3];62(9):2569–81. Available from: https://pubmed.ncbi.nlm.nih.gov/20872595/Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, et al. The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the - and -Chains of Fibrin. J Immunol. 2001 Mar;166(6):4177–84.Bang H, Egerer K, Gauliard A, Lüthke K, Rudolph PE, Fredenhagen G, et al. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007 Aug;56(8):2503–11.Kinloch A, Tatzer V, Wait R, Peston D, Lundberg K, Donatien P, et al. Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis. Arthritis Res Ther. 2005;7(6):R1421-9.Jones V, Taylor PC, Jacoby RK, Wallington TB. Synovial synthesis of rheumatoid factors and immune complex constituents in early arthritis. Ann Rheum Dis. 1984 Apr;43(2):235–9Quirke A-M, Fisher BAC, Kinloch AJ, Venables PJ. Citrullination of autoantigens: Upstream of TNFα in the pathogenesis of rheumatoid arthritis. FEBS Lett. [Internet] 2011 Dec [cited 2020 Aug 18];585(23):3681–8. Available from: https://pubmed.ncbi.nlm.nih.gov/21704035/Vander Cruyssen B, Cantaert T, Nogueira L, Clavel C, De Rycke L, Dendoven A, et al. Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays. Arthritis Res Ther. [Internet] 2006 [cited 2020 Aug 20];8(4):R122. Available form: https://pubmed.ncbi.nlm.nih.gov/16859515/Chapuy-Regaud S, Nogueira L, Clavel C, Sebbag M, Vincent C, Serre G. IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin. Clin Exp Immunol. [Internet] 2005 Mar[cited 2020 Aug 23];139(3):542–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18093McInnes IB, Schett G. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med [Internet]. 2011 Dec 8 [cited 2019 Mar 15];365(23):2205–19. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMra1004965Marcinkiewicz J, Biedroń R, Maresz K, Kwaśny-Krochin B, Bobek M, Kontny E, et al. Oxidative modification of type II collagen differentially affects its arthritogenic and tolerogenic capacity in experimental arthritis. Arch Immunol Ther Exp (Warsz). 52(4):284– 91. https://pubmed.ncbi.nlm.nih.gov/15467493/Shi J, Knevel R, Suwannalai P, van der Linden MP, Janssen GMC, van Veelen P a., et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc Natl Acad Sci. [Internet] 2011 [cited 2019 Jun 8];108(42):17372–7. Available from: https://pubmed.ncbi.nlm.nih.gov/21987802/Eggleton P, Nissim A, Ryan BJ, Whiteman M, Winyard PG. Detection and isolation of human serum autoantibodies that recognize oxidatively modified autoantigens. Free Radic Biol Med. [internet] 2013 Apr [cited 2019 Jun 10];57:79–91. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0891584912018060Steinbrecher UP, Fisher M, Witztum JL, Curtiss LK. Immunogenicity of homologous low density lipoprotein after methylation, ethylation, acetylation, or carbamylation: generation of antibodies specific for derivatized lysine. J Lipid Res. 1984 Oct;25(10):1109–16.Valesini G, Gerardi MC, Iannuccelli C, Pacucci VA, Pendolino M, Shoenfeld Y. Citrullination and autoimmunity. Autoimmun Rev. [Internet] 2015 Jun [cited 2019 Jun 15];14(6):490–7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1568997215000282Bax M, van Heemst J, Huizinga TWJ, Toes REM. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics. 2011 Aug;63(8):459–66. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132380/O’Dell J. Rheumatoid arthritis. In: Goldman L, Schafer AI E, editor. Goldman’s Cecil Medicine. 25th ed. Philadelphia: Elsevier Saunders; 2016.Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum [Internet]. 1987 Nov [cited 2019 Apr 9];30(11):1205–13. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2446635Nell VPK. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005 Dec;64(12):1731Hutchinson D, Shepstone L, Moots R, Lear JT, Lynch MP. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis. 2001 Mar;60(3):223–7. Available from: https://pubmed.ncbi.nlm.nih.gov/11171682/Källberg H, Ding B, Padyukov L, Bengtsson C, Rönnelid J, Klareskog L, et al. Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks after various exposures to cigarette smoke. Ann Rheum Dis. 2011 Mar;70(3):508–11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033966/pdf/nihms 263734.pdfKarlson EW, Lee IM, Cook NR, Manson JE, Buring JE, Hennekens CH. A retrospective cohort study of cigarette smoking and risk of rheumatoid arthritis in female health professionals. Arthritis Rheum. 1999 May;42(5):910–7. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1002/1529- 0131%28199905%2942%3A5%3C910%3A%3AAID-ANR9%3E3.0.CO%3B2-DKlareskog L, Malmström V, Lundberg K, Padyukov L, Alfredsson L. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Semin Immunol. 2011 Apr;23(2):92–8.Klareskog L, Stolt P, Lundberg K, Källberg H, Bengtsson C, Grunewald J, et al. A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum. 2006 Jan;54(1):38–46.Makrygiannakis D, Hermansson M, Ulfgren A-K, Nicholas AP, Zendman AJW, Eklund A, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis. 2008 Oct;67(10):1488–92.Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004 Oct;50(10):3085–92.Linn-Rasker SP. Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis. 2006 Mar;65(3):366–71.Pedersen M, Jacobsen S, Garred P, Madsen HO, Klarlund M, Svejgaard A, et al. Strong combined gene–environment effects in anti–cyclic citrullinated peptide– positive rheumatoid arthritis: A nationwide case–control study in Denmark. Arthritis Rheum. 2007 May;56(5):1446–53.Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L. Gene environment interaction between the DRB1 shared epitope and smoking in the risk of anti-citrullinated protein antibody-positive rheumatoid arthritis: All alleles are important. Arthritis Rheum. 2009 Jun;60(6):1597–603.Wernick RM, Lipsky PE, Marban-Arcos E, Maliakkal JJ, Edelbaum D, Ziff M. IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures. Arthritis Rheum. 1985 Jul;28(7):742–52.Mysak J, Podzimek S, Sommerova P, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. [Internet] 2014 Mar [Cited 2022 25 Feb]; 2014 (47) 60-68. Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984870/#Bostanci N, Belibasakis G. Porphyromonas gingivalis: an invasive and evasive opportunistic oral pathogen. FEMS Microbiology Letters [Internet] 2012 Aug [Cited 2022 20 Mar]; 333 (1): 1-9 Avilable in: https://academic.oup.com/femsle/article/333/1/1/586464?login=falseKoziel J, Mydel P, Potempa J. The Link Between Periodontal Disease and Rheumatoid Arthritis: An Updated Review. Curr Rheumatol Rep. [Internet] 2014 Jan [Cited 2022 26 Mar]; 16(3): 408 Avilable in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930831/Lamont RJ, Jenkinson HF. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev. 1998 Dec;62(4):1244–63.Manga P, Wegner N, Venables PJ, Potempa J. Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis? Arthritis Res Ther. 2010;12(3):209.Koziel J, Mydel P, Potempa J. The link between periodontal disease and rheumatoid arthritis: an updated review. Curr Rheumatol Rep. 2014 Mar;16(3):408.Socransky SS, Haffajee AD. Effect of Therapy on Periodontal Infections. J Periodontol. 1993 Aug;64(8s):754–9.Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonas gingivalis. Periodontol 2000. 1999 Jun;20:168–238.Kesavalu L, Holt SC, Ebersole JL. Trypsin-like protease activity of Porphyromonas gingivalis as a potential virulence factor in a murine lesion model. Microb Pathog. 1996 Jan;20(1):1–10.Birkedal-Hansen H, Taylor RE, Zambon JJ, Barwa PK, Neiders ME. Characterization of collagenolytic activity from strains of Bacteroides gingivalis. J Periodontal Res. 1988 Jul;23(4):258–64.McGraw WT, Potempa J, Farley D, Travis J. Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun. 1999 Jul;67(7):3248–56.Wegner N, Wait R, Sroka A, Eick S, Nguyen K-A, Lundberg K, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: Implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum [Internet]. 2010 Sep [cited 2019 Jul 29];62(9):2662–72. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20506214Batool H, Afzal N, Shahzad F, Kashif M. Relationship between rheumatoid arthritis and chronic periodontitis. J Med Radiol Pathol Surg. 2016;2(6):11–4.Rodríguez SB, Stitt BL, Ash DE. Cysteine 351 is an essential nucleophile in catalysis by Porphyromonas gingivalis peptidylarginine deiminase. Arch Biochem Biophys. 2010 Dec;504(2):190–6.Farquharson D, Butcher JP, Culshaw S. Periodontitis, Porphyromonas, and the pathogenesis of rheumatoid arthritis. Mucosal Immunol [Internet]. 2012;5(2):112– 20. Available from: http://dx.doi.org/10.1038/mi.2011.66Brinkmann V. Neutrophil Extracellular Traps Kill Bacteria. Science (80- ). 2004 Mar;303(5663):1532–5.Brinkmann V, Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat Rev Microbiol. 2007 Aug;5(8):577–82.Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008 Feb;180(3):1895–902.Liubomorova I. State of periodontium in patients affected with rheumatism. Stomatologiia (Mosk). 1964;33 – 37.Mercado FB, Marshall RI, Klestov AC, Bartold PM. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001 Jun;72(6):779–87.Arkema E V., Karlson EW, Costenbader KH. A Prospective Study of Periodontal Disease and Risk of Rheumatoid Arthritis. J Rheumatol. 2010 Sep;37(9):1800–4.Abdelsalam SK, Hashim NT, Elsalamabi EM, Gismalla BG. Periodontal status of rheumatoid arthritis patients in khartoum state. BMC Res Notes. 2011;4(1):460.89. Gleissner C, Willershausen B, Kaesser U, Bolten WW. The role of risk factors for periodontal disease in patients with rheumatoid arthritis. Eur J Med Res. 1998 Aug;3(8):387–92.90. Kässer UR, Gleissner C, Dehne F, Michel A, Willershausen-Zönnchen B, Bolten WW. Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum. 1997 Dec;40(12):2248–51.91. Cooles FAH, Isaacs JD. Pathophysiology of rheumatoid arthritis. Curr Opin Rheumatol. 2011 May;23(3):233–40.InflamaciónBacteriaEnzimaAnticuerposPeriodontitisAutoinmunidadORIGINALPinilla Torres Laura Lizeth.pdfPinilla Torres Laura Lizeth.pdfapplication/pdf835582https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/1/Pinilla%20Torres%20Laura%20Lizeth.pdf41d1af1b8f6ab5fa93919f573d160295MD51open accessPinilla Torres Laura Lizeth.pptx.pdfPinilla Torres Laura Lizeth.pptx.pdfapplication/pdf1588078https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/2/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf16dcb80aa80672da00c9794b435ec286MD52open accessCARTA DERECHOS DE AUTOR Pinilla.pdfCARTA DERECHOS DE AUTOR Pinilla.pdfapplication/pdf188027https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/3/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf2353f0e3f87651c3086cebcdd1ded829MD53metadata only access1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdf1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdfapplication/pdf735205https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/4/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdfe24a90df09b81a51c81795fadd4b6a85MD54metadata only accessLICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/5/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD55open accessTEXTPinilla Torres Laura Lizeth.pdf.txtPinilla Torres Laura Lizeth.pdf.txtExtracted texttext/plain116508https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/6/Pinilla%20Torres%20Laura%20Lizeth.pdf.txte9b2325950e37c260e781b914cabedb0MD56open accessPinilla Torres Laura Lizeth.pptx.pdf.txtPinilla Torres Laura Lizeth.pptx.pdf.txtExtracted texttext/plain12279https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/8/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf.txtc82b8b4119f274a4d8ceae29472e5222MD58open accessCARTA DERECHOS DE AUTOR Pinilla.pdf.txtCARTA DERECHOS DE AUTOR Pinilla.pdf.txtExtracted texttext/plain1142https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/10/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf.txt74f16f331746e8c35008f5d57de37c04MD510metadata only access1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdf.txt1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdf.txtExtracted texttext/plain3034https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/12/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdf.txtaeaad6a1c45cbdba719b87bbd40e9c32MD512metadata only accessTHUMBNAILPinilla Torres Laura Lizeth.pdf.jpgPinilla Torres Laura Lizeth.pdf.jpgGenerated Thumbnailimage/jpeg6405https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/7/Pinilla%20Torres%20Laura%20Lizeth.pdf.jpgf1a0710d4dfcb45d5a2f3a7239411bbdMD57open accessPinilla Torres Laura Lizeth.pptx.pdf.jpgPinilla Torres Laura Lizeth.pptx.pdf.jpgGenerated Thumbnailimage/jpeg4955https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/9/Pinilla%20Torres%20Laura%20Lizeth.pptx.pdf.jpga80819607e4c73b2842ddcd9d4db0095MD59open accessCARTA DERECHOS DE AUTOR Pinilla.pdf.jpgCARTA DERECHOS DE AUTOR Pinilla.pdf.jpgGenerated Thumbnailimage/jpeg9600https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/11/CARTA%20DERECHOS%20DE%20AUTOR%20Pinilla.pdf.jpg79ade22e04f4e186a5c1a3c42d94dcbdMD511metadata only access1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdf.jpg1.FORMATO IDENTIFICACIÓN TRABAJOS DE GRADO-am (1) (2).pdf.jpgGenerated Thumbnailimage/jpeg12051https://repositorio.unicolmayor.edu.co/bitstream/unicolmayor/5674/13/1.FORMATO%20IDENTIFICACI%c3%93N%20TRABAJOS%20DE%20GRADO-am%20%281%29%20%282%29.pdf.jpg64054b136184a739c9f8e3d06149b2eaMD513metadata only accessunicolmayor/5674oai:repositorio.unicolmayor.edu.co:unicolmayor/56742024-05-09 16:49:40.953An error occurred on the license name.|||https://creativecommons.org/licenses/by-nc-sa/4.0/open accessBiblioteca Digital Unicolmayorrepositorio@unicolmayor.edu.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