Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Each myositis specific autoantibodies (MSA) are associated with unique clinical subset and useful biomarkers in polymyositis/dermatomyositis (PM/DM). Identifying new MSA will help in monitoring PM/DM patients as evidenced recently by reports on anti-TIF1gamma (transcription intermediary factor-1gamma) associated with malignancy and anti-MDA5 associated with clinically amyopathic DM with rapidly progressive interstitial lung disease (ILD). Although new autoantibody specificities have been added, ~50% of patients with PM/DM are still without known MSA, thus identifying additional MSA is relevant. A set of 3 proteins of ~120 -160kD recognized by serum from patients with DM were noticed and the antigens and clinical features of patients with this autoantibody specificity were characterized.
A set of 3 proteins of ~120 -160kD recognized by a prototype serum was purified and identified by mass spectrometry. Sera from ~2200 patients with various diagnosis including 434 SLE, 119 scleroderma, and 514 PM/DM from 4 countries were tested by immunoprecipitation of 35S-methionine labeled K562 cell extract. Sera that immunoprecipitated the same set of proteins were searched and identity of specificity was verified by immunoprecipitation and western blot using mouse monoclonal antibodies (mAb). Clinical information was from database and charts.
Results: Many peptides covering 50+% of the whole sequence for cohesion subunit SA-1, SA-2 and SMC3 (structural maintenance of chromosome) were detected from purified ~120-160kD proteins. Identity of the proteins immunoprecipitated by human autoimmune sera was confirmed by probing immunoprecipitated proteins by mouse mAb to components of cohesion complex, SA-1, SA-2, SMC1 and Rad21. IP pattern of 3 bands by anti-SA-2 mAb appeared to be same as that by human autoimmune sera. Based on these findings, it was concluded that the set of proteins recognized by the autoimmune sera was cohesion complex, which is known to regulate the separation of sister chromatids during cell division, and also involved in various functions such as controlling gene expression, DNA replication and DNA repair. All 4 anti-cohesin autoimmune sera showed fine speckled nuclear staining sparing nucleoli by immunofluorescence antinuclear antibodies. Despite localization of cohesion on chromosomes, staining of mitotic chromosomes was not clear. Four cases with anti-cohesin were identified; 3 females (2 African Americans, 1 Latin) and a male (Japanese). A Japanese patient was amyopathic DM with ILD. A Latin patient had DM and an African American patient had PM-SSc overlap syndrome with ILD and positive for anti-U1RNP and Su/Argonaute2 antibodies. Another American patient had Raynaud’s phenomenon and skin ulcer/gangrene. None of these patients had cancer or coexisting MSA or SSc-specific autoantibodies. This specificity was not found in SLE, scleroderma, or other conditions.
Conclusion: Anti-cohesin complex is a new autoantibody specificity that appears to be associated with PM/DM and ILD. Whether it has association with unique features will need to be evaluated in future studies.
To cite this abstract in AMA style:Tanaka S, Calise SJ, Satoh Y, Tanaka Y, Vazquez-Del Mercado M, Medrano-Ramírez G, Sobel ES, Reeves WH, Chan EKL, Satoh M. Cohesin Complex Is a New Myositis Autoantigen [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/cohesin-complex-is-a-new-myositis-autoantigen/. Accessed October 19, 2021.
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