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

Nina Wolska, Paulina Rybakowska, Astrid Rasmussen, Michael Brown, Courtney Montgomery, Arkadiusz Klopocki, Kiely Grundahl, Robert H. Scofield, Lida Radfar, Donald U. Stone, Juan M. Anaya, John A. Ice, Christopher J. Lessard, David M. Lewis, Nelson L. Rhodus, Rajaram Gopalakrishnan, Andrew J.W. Huang, Pamela J. Hughes, Michael D. Rohrer, Michael H. WeismanSwamy Venuturupalli, Joel M. Guthridge, Judith A. James, Kathy L. Sivils, Harini Bagavant, Umesh S. Deshmukh

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)724-729
Number of pages6
JournalArthritis and Rheumatology
Issue number3
StatePublished - Mar 1 2016

Bibliographical note

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.


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