{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:38:01Z","timestamp":1793144281069,"version":"4.5.0"},"reference-count":49,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sj\u00f6gren's disease (SjD) is a heterogeneous autoimmune disorder characterized by substantial clinical and molecular diversity. This heterogeneity raises key questions regarding the existence of distinct pathogenic mechanisms underlying disease subtypes. The objective of this study was to comprehensively characterize peripheral immune cell states associated with SjD and to identify features that could enable better patient stratification for targeted treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single\u2010cell RNA sequencing with surface protein profiling on 1.5 million peripheral blood mononuclear cells from 333 participants. Individuals were stratified by SjD diagnosis and anti\u2010SSA status to enable comparative analyses between disease subgroups and controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis identified two immunologic endotypes of SjD, with SSA\u2010positive participants exhibiting a dominant and persistent type I interferon signature that was also associated with altered immune cell composition. Transitional B cells were particularly affected, displaying altered developmental states, reduced BCR diversity, shorter CDR3 regions, and increased predicted interactions with activated immune cell populations, findings consistent with perturbations of early B cell selection processes. By contrast, SSA\u2010negative participants with SjD exhibited limited transcriptional differences compared with symptomatic non\u2010SjD controls, highlighting substantial biologic heterogeneity within SjD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support a two\u2010disease model of SjD and highlight transitional B cells as both a key biomarker and a therapeutic target.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70320-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70320","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:58:05Z","timestamp":1788771485000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Single\u2010Cell\n                    <scp>RNA<\/scp>\n                    Sequencing of Peripheral Blood Defines Two Immunologic Subtypes of Sj\u00f6gren's Disease Distinguished by Anti\u2010\n                    <scp>SSA<\/scp>\n                    Antibodies and Aberrant B Cell Populations"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-8423","authenticated-orcid":false,"given":"Geoffrey","family":"Urbanski","sequence":"first","affiliation":[{"name":"Department of Orofacial Sciences University of California  San Francisco California"},{"name":"CoLabs Initiative University of California  San Francisco California"},{"name":"Division of Immunology and Allergology, Laboratory of Translational Immunology, Department of Medicine H\u00f4pitaux Universitaires de Gen\u00e8ve  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly E.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Flynn","sequence":"additional","affiliation":[{"name":"CoLabs Initiative University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armita","family":"Norouzi","sequence":"additional","affiliation":[{"name":"CoLabs Initiative University of California  San Francisco California"},{"name":"School of Medicine University of Washington  Seattle 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K.","family":"Patel","sequence":"additional","affiliation":[{"name":"CoLabs Initiative University of California  San Francisco California"},{"name":"Division of Rheumatology, Department of Medicine University of California  San Francisco California"},{"name":"Bakar ImmunoX Initiative University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie W.","family":"Poon","sequence":"additional","affiliation":[{"name":"CoLabs Initiative University of California  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela K.","family":"Fragiadakis","sequence":"additional","affiliation":[{"name":"CoLabs Initiative University of California  San Francisco California"},{"name":"Division of Rheumatology, Department of Medicine University of California  San Francisco California"},{"name":"Bakar ImmunoX Initiative University of California  San Francisco 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