{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:57:05Z","timestamp":1781672225713,"version":"3.54.5"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["F31DE034904"],"award-info":[{"award-number":["F31DE034904"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["UC2AR081032, P30AR073750, P50AR060804, R01AR073855, R01AR065953"],"award-info":[{"award-number":["UC2AR081032, P30AR073750, P50AR060804, R01AR073855, R01AR065953"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI176244"],"award-info":[{"award-number":["U01AI176244"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Incomplete lupus erythematosus (ILE) and non-Sj\u00f6gren\u2019s disease sicca (nSjD-sicca) are clinically heterogeneous, incompletely classified autoimmune conditions that share features with systemic lupus erythematosus (SLE) and Sj\u00f6gren\u2019s disease (SjD), respectively. Although some patients progress to classified disease, many remain stable. The immunologic features distinguishing incomplete from established autoimmune disease remain poorly defined. We sought to characterize and compare autoantibody immune signatures across ILE, SLE, nSjD-sicca, and SjD using expanded autoantibody profiling. Serum samples were obtained from patients with ILE (n=80), SLE (n=80), nSjD-sicca (n=52), SjD (n=60), and matched healthy controls (n=79). Initial screening was performed using the Bio-Rad BioPlex 2200. Expanded profiling utilized the GeneCopoeia Human Autoimmune Array (120 autoantigens) with parallel IgM and IgG detection. Traditional screening demonstrated expected patterns: ILE (anti-nRNP 26.3%; anti-chromatin 25.0%), SLE (anti-SmRNP 40.0%; anti-dsDNA 31.3%), nSjD-sicca (anti-La 9.6%), and SjD (anti-Ro\/SSA 53.3%). Expanded analysis revealed significantly increased IgM autoreactivity in ILE compared with SLE (BH-FDR-adjusted p&amp;lt;0.05), targeting nuclear (KU, Nup62, CENP-A\/B), cytokine (IFN-\u03b11, IFN-\u03f5, IL-15, GM-CSF), mitochondrial (M2), extracellular matrix (collagen IV, fibrinogen), vascular (\u03b22-glycoprotein I, AGTR), and gut-associated antigens (tissue transglutaminase, intrinsic factor). In contrast, SLE demonstrated enriched IgG responses to canonical nuclear antigens, including core histone and dsDNA. Within the sicca spectrum, Ro52 (TRIM21) IgG autoantibodies were significantly increased in SjD compared to nSjD-sicca. These findings indicate that incomplete autoimmune disease states exhibit distinct IgM-dominant autoantibody profiles rather than simply attenuated versions of the IgG dominant responses in classified disease, highlighting the potential value of isotype-specific profiling for disease classification.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1847217","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:49:02Z","timestamp":1781671742000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct IgM and IgG autoantibody profiles characterize incomplete and classified systemic autoimmune diseases"],"prefix":"10.3389","volume":"17","author":[{"given":"Rebecca A.","family":"Wood","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Campus","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Kodali","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Redinger","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Darise","family":"Farris","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Campus","place":["Oklahoma City, OK, United States"]},{"name":"Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Lessard","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Campus","place":["Oklahoma City, OK, United States"]},{"name":"Genes & Human Disease Research Program, Oklahoma Medical Research Foundation","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Hal","family":"Scofield","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Oklahoma Health Campus","place":["Oklahoma City, OK, United States"]},{"name":"Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation","place":["Oklahoma City, OK, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42330","article-title":"Increasing prevalence of antinuclear antibodies in the United States","volume":"74","author":"Dinse","year":"2022","journal-title":"Arthritis Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00457-9","article-title":"Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK","volume":"401","author":"Conrad","year":"2023","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/acr.23201","article-title":"Clinical and serologic features in patients with incomplete lupus classification versus systemic lupus erythematosus patients and controls","volume":"69","author":"Aberle","year":"2017","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24003","article-title":"American Indians have a higher risk of Sjogren's syndrome and more disease activity than European Americans and African Americans","volume":"72","author":"Scofield","year":"2020","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5417","DOI":"10.1038\/s41467-021-25509-3","article-title":"New-onset IgG autoantibodies in hospitalized patients with COVID-19","volume":"12","author":"Chang","year":"2021","journal-title":"Nat Commun"},{"key":"B6","volume-title":"Primer on the Rheumatic Diseases","author":"Klippel","year":"2007"},{"key":"B7","article-title":"Sjogren syndrome","volume-title":"StatPearls","author":"Carsons","year":"2023"},{"key":"B8","doi-asserted-by":"publisher","first-page":"313","DOI":"10.21037\/atm.2017.05.07","article-title":"Classification criteria in Sjogren's syndrome","volume":"5","author":"Baldini","year":"2017","journal-title":"Ann Trans Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2016.03.002","article-title":"Autoantibodies in sjogren's syndrome","volume":"42","author":"Fayyaz","year":"2016","journal-title":"Rheum Dis Clin North Am"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.09.013","article-title":"Novel autoantibodies in Sjogren's syndrome","volume":"145","author":"Shen","year":"2012","journal-title":"Clin Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2016.1196676","article-title":"A re-evaluation of anti-NA-14 antibodies in patients with primary Sjogren's syndrome: Significant role of interferon-gamma in the production of autoantibodies against NA-14","volume":"49","author":"Uomori","year":"2016","journal-title":"Autoimmunity"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/art.40930","article-title":"2019 European League Against Rheumatism\/American College of Rheumatology classification criteria for systemic lupus erythematosus","volume":"71","author":"Aringer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780231107","article-title":"Serologic subsets in systemic lupus-erythematosus - 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