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Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity
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Wolska, Nina
Rybakowska, Paulina
Rasmussen, Astrid
Brown, Michael
Montgomery, Courtney
Klopocki, Arkadiusz
Grundahl, Kiely
Scofield, Robert H
Radfar, Lida
Stone, Donald U
Fecha
2016
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John Wiley and Sons Inc.
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Abstract
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.
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Keywords
Autoantibody , human , 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 , Trim38 protein , 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
