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B cells and autoantibodies have been associated with IPAH and identified as potential therapeutic targets. However, the specific populations of B cells involved and their roles in disease pathogenesis are not clearly defined. We aimed to assess the levels of activated B cells (plasmablasts) in IPAH, and to characterize recombinant antibodies derived from these plasmablasts. Blood plasmablasts are elevated in IPAH, remain elevated over time, and produce IgA autoantibodies. Single\u2010cell sequencing of plasmablasts in IPAH revealed repertoires of affinity\u2010matured antibodies with small clonal expansions, consistent with an ongoing autoimmune response. Recombinant antibodies representative of these clonal lineages bound known autoantigen targets and displayed an unexpectedly high degree of polyreactivity. Representative IPAH plasmablast recombinant antibodies stimulated human umbilical vein endothelial cells to produce cytokines and overexpress the adhesion molecule ICAM\u20101. Together, our results demonstrate an ongoing adaptive autoimmune response involving IgA plasmablasts that produce anti\u2010endothelial cell autoantibodies in IPAH. These antibodies stimulate endothelial cell production of cytokines and adhesion molecules, which may contribute to disease pathogenesis. These findings suggest a role for mucosally\u2010driven autoimmunity and autoimmune injury in the pathogenesis of IPAH.<\/jats:p>","DOI":"10.1002\/eji.201747460","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T10:22:44Z","timestamp":1516875764000},"page":"874-884","source":"Crossref","is-referenced-by-count":40,"title":["Circulating plasmablasts are elevated and produce pathogenic anti\u2010endothelial cell autoantibodies in idiopathic pulmonary arterial hypertension"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-8939","authenticated-orcid":false,"given":"Lisa K.","family":"Blum","sequence":"first","affiliation":[{"name":"Stanford University School of Medicine Division of Immunology and Rheumatology  Stanford CA USA"},{"name":"VA Palo Alto Health Care System  Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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