TY - JOUR
T1 - Patients with Primary Sjögren's Syndrome Who Are Positive for Autoantibodies to Tripartite Motif-Containing Protein 38 Show Greater Disease Severity
AU - Wolska, Nina
AU - Rybakowska, Paulina
AU - Rasmussen, Astrid
AU - Brown, Michael
AU - Montgomery, Courtney
AU - Klopocki, Arkadiusz
AU - Grundahl, Kiely
AU - Scofield, Robert H.
AU - Radfar, Lida
AU - Stone, Donald U.
AU - Anaya, Juan M.
AU - Ice, John A.
AU - Lessard, Christopher J.
AU - Lewis, David M.
AU - Rhodus, Nelson L.
AU - Gopalakrishnan, Rajaram
AU - Huang, Andrew J.W.
AU - Hughes, Pamela J.
AU - Rohrer, Michael D.
AU - Weisman, Michael H.
AU - Venuturupalli, Swamy
AU - Guthridge, Joel M.
AU - James, Judith A.
AU - Sivils, Kathy L.
AU - Bagavant, Harini
AU - Deshmukh, Umesh S.
N1 - Funding Information:
Supported by NIH grants U54-GM-104938, P30-AR-053483, P30-GM-103510, and U19-AI-082714 to Dr. James, NIH grant P50-AR-060804 to Dr. Sivils, and funding from the Oklahoma Medical Research Foundation to Dr. Deshmukh.
Publisher Copyright:
© 2016, American College of Rheumatology.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84963864722
UR - https://www.scopus.com/pages/publications/84963864722#tab=citedBy
U2 - 10.1002/art.39497
DO - 10.1002/art.39497
M3 - Research Article
C2 - 26636433
AN - SCOPUS:84963864722
SN - 2326-5191
VL - 68
SP - 724
EP - 729
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
IS - 3
ER -