Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity

Objective Autoantibodies reactive with Ro52 (tripartite motif-containing protein 21 [TRIM21]) are detected in 70% of patients with primary Sjögren's syndrome (SS). TRIM21 belongs to a 34-member C-IV family of TRIM proteins. Although autoantibodies against other TRIM proteins within the C-IV family have been detected in the sera of patients with primary SS, their clinical relevance remains unclear. This study was undertaken to investigate the frequency of anti-TRIM38 in patients with primary SS and evaluate its association with various clinical measures of the disease. Methods Serum samples from patients with primary SS (n = 235) and controls (n = 50) were analyzed for reactivity with in vitro-transcribed and -translated 35S-methionine-labeled TRIM38 protein. The associations of anti-TRIM38 with various laboratory and clinical measures of primary SS were evaluated. Reactivity of anti-TRIM38 with different structural domains of TRIM38 was analyzed. Affinity-purified anti-TRIM38 antibodies were used to immunoprecipitate TRIM21. Results TRIM38-reactive autoantibodies were detected in the sera of 24 of the 235 patients with primary SS and 2 of the 50 controls. Anti-TRIM38 positivity was significantly associated with the presence of anti-Ro60, anti-Ro52, anti-La, rheumatoid factor, and hypergammaglobulinemia. Clinically, anti-TRIM38 was associated with significantly higher ocular surface staining scores, lower Schirmer's test scores, and minor labial salivary gland biopsy focus scores of ?3.0. Anti-TRIM38 antibodies mainly recognized the cortactin-binding protein 2 (CortBP-2; amino acids 128-238) and the B30.2/SPRY (amino acids 268-465) domains on TRIM38. Affinity-purified antibodies to TRIM38-CortBP-2 and TRIM38-B30.2/SPRY domains reacted with TRIM21. Conclusion Our data demonstrate that anti-TRIM38 specificity arising in a subset of patients with primary SS is associated with increased severity of the disease. © 2016, American College of Rheumatology.

• Fecha de publicación: 2016
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23011
• Acceso en línea: https://doi.org/10.1002/art.39497; https://repository.urosario.edu.co/handle/10336/23011
• Palabra clave: Autoantibody; Cortactin; Cortactin binding protein 2; La antibody; Membrane protein; Rheumatoid factor; Ro52 antibody; Ro60 antibody; Tripartite motif containing protein 21; Tripartite motif containing protein 38; Unclassified drug; Autoantibody; Carrier protein; Methionine; Rheumatoid factor; Ribonucleoprotein; Ss-a antigen; Sulfur; Adult; Antibody blood level; Antibody detection; Antibody specificity; Article; Controlled study; Disease severity; Female; Human; Hypergammaglobulinemia; Immunoprecipitation; Major clinical study; Male; Middle aged; Nonhuman; Priority journal; Protein domain; Protein family; Salivary gland biopsy; Schirmer test; Sjoegren syndrome; Blood; Immunology; Pathophysiology; Severity of illness index; Sjoegren syndrome; Autoantibodies; Carrier proteins; Female; Humans; Hypergammaglobulinemia; Immunoprecipitation; Male; Methionine; Middle aged; Rheumatoid factor; Ribonucleoproteins; Severity of illness index; Sjogren's syndrome; Sulfur radioisotopes; human; Trim38 protein
• License: Abierto (Texto Completo)