{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:40:47Z","timestamp":1793166047585,"version":"4.5.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases)","award":["T32-AR-07534"],"award-info":[{"award-number":["T32-AR-07534"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["U01-AI-101981"],"award-info":[{"award-number":["U01-AI-101981"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The disease process in rheumatoid arthritis (RA) starts years before the clinical diagnosis is made, and elevated levels of disease\u2010specific autoantibodies can be detected during this period. Early responses to known or novel autoantigens likely drive the eventual production of pathogenic autoimmunity. Importantly, the presence of disease\u2010specific autoantibodies can identify individuals who are at high risk of developing RA but who do not currently have arthritis. The goal of the current study was to characterize plasmablasts from individuals at risk of developing RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated antibody\u2010secreting plasmablasts derived from a well\u2010characterized cohort of individuals who were at risk of developing RA, based on RA\u2010related serum autoantibody positivity, as compared to patients with early (&lt;1 year) seropositive RA as well as healthy control subjects. The plasmablast antibody repertoires of at\u2010risk subjects were analyzed using DNA barcode\u2013based methods with paired heavy\u2010 and light\u2010chain gene sequencing. Cells were single\u2010cell sorted, the cell\u2010 and plate\u2010specific DNA barcodes were sequentially added, and next\u2010generation sequencing was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total plasmablast levels were similar in the antibody\u2010positive (1%) and control (0.4\u20131.6%) groups. However, increased frequencies of IgA+ versus IgG+ plasmablasts were observed in the antibody\u2010positive group (39% IgA+ and 37% IgG+) as compared to other groups (1\u20139% IgA+ and 71\u201087% IgG+). Paired antibody sequences from antibody\u2010positive subjects revealed cross\u2010isotype clonal families and similar sequence characteristics in the IgA and IgG plasmablast repertoires. Antibody\u2010positive individuals also demonstrated elevated serum levels of IgA isotype anti\u2013cyclic citrullinated peptide 3 antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The IgA plasmablast dominance in these antibody\u2010positive individuals suggests that a subset of RA\u2010related autoantibodies may arise from mucosal immune responses and may be involved in early disease pathogenesis in individuals who are at risk of developing RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39771","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T09:02:51Z","timestamp":1465203771000},"page":"2372-2383","source":"Crossref","is-referenced-by-count":94,"title":["Elevated IgA Plasmablast Levels in Subjects at Risk of Developing Rheumatoid Arthritis"],"prefix":"10.1002","volume":"68","author":[{"given":"Jennifer D.","family":"Kinslow","sequence":"first","affiliation":[{"name":"University of Colorado School of Medicine Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Blum","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine Aurora"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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