{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:17:35Z","timestamp":1790216255128,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,9,26]],"date-time":"2014-09-26T00:00:00Z","timestamp":1411689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AR063676"],"award-info":[{"award-number":["AR063676"]}]},{"name":"NIH","award":["HV-00242"],"award-info":[{"award-number":["HV-00242"]}]},{"name":"NIH","award":["AI101981"],"award-info":[{"award-number":["AI101981"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A hallmark of rheumatoid arthritis (RA) is the production of autoantibodies, including anti\u2013citrullinated protein antibodies (ACPAs). Nevertheless, the specific targets of these autoantibodies remain incompletely defined. During an immune response, B cells specific for the inciting antigen(s) are activated and differentiate into plasmablasts, which are released into the blood. We undertook this study to sequence the plasmablast antibody repertoire to define the targets of the active immune response in RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We developed a novel DNA barcoding method to sequence the cognate heavy\u2010 and light\u2010chain pairs of antibodies expressed by individual blood plasmablasts in RA. The method uses a universal 5\u2032 adapter that enables full\u2010length sequencing of the antibodies' variable regions and recombinant expression of the paired antibody chains. The sequence data sets were bioinformatically analyzed to generate phylogenetic trees that identify clonal families of antibodies sharing heavy\u2010 and light\u2010chain VJ sequences. Representative antibodies were expressed, and their binding properties were characterized using anti\u2013cyclic citrullinated peptide 2 (anti\u2013CCP\u20102) enzyme\u2010linked immunosorbent assay (ELISA) and antigen microarrays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We used our sequencing method to generate phylogenetic trees representing the antibody repertoires of peripheral blood plasmablasts from 4 individuals with anti\u2010CCP+ RA, and recombinantly expressed 14 antibodies that were either \u201csingleton\u201d antibodies or representative of clonal antibody families. Anti\u2013CCP\u20102 ELISA identified 4 ACPAs, and antigen microarray analysis identified ACPAs that differentially targeted epitopes on \u03b1\u2010enolase, citrullinated fibrinogen, and citrullinated histone H2B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data provide evidence that autoantibodies targeting \u03b1\u2010enolase, citrullinated fibrinogen, and citrullinated histone H2B are produced by the ongoing activated B cell response in, and thus may contribute to the pathogenesis of, RA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38754","type":"journal-article","created":{"date-parts":[[2014,6,25]],"date-time":"2014-06-25T11:19:30Z","timestamp":1403695170000},"page":"2706-2715","source":"Crossref","is-referenced-by-count":103,"title":["Barcode\u2010Enabled Sequencing of Plasmablast Antibody Repertoires in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Yann\u2010Chong","family":"Tan","sequence":"first","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kongpachith","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"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":"Chia\u2010Hsin","family":"Ju","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren J.","family":"Lahey","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Lu","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Cai","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Stanford University, Stanford, California, and VA Palo Alto Health Care System Palo Alto 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