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Patients positive for Sj\u00f6gren's syndrome antigen A\/Sj\u00f6gren syndrome antigen B (SSA\/SSB) autoantibodies are more prone to systemic disease manifestations and adverse outcomes. We aimed to determine the role of B cell composition, gene expression, and B cell receptor usage in pSS subgroups stratified for SSA\/SSB antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Over 230,000 B cells were isolated from peripheral blood of patients with pSS (n\u00a0=\u00a06 SSA\u2212, n\u00a0=\u00a08 SSA+ single positive and n\u00a0=\u00a010 SSA\/SSB+ double positive) and four healthy controls and processed for single\u2010cell RNA sequencing (scRNA\u2010seq) and single\u2010cell variable, diversity, and joining (VDJ) gene sequencing (scVDJ\u2010seq).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that SSA\/SSB+ patients present the highest and lowest proportion of na\u00efve and memory B cells, respectively, and the highest up\u2010regulation of interferon\u2010induced genes across all B cell subtypes. Differential usage of\n                      <jats:italic>IGHV<\/jats:italic>\n                      showed that\n                      <jats:italic>IGHV1\u201069<\/jats:italic>\n                      and\n                      <jats:italic>IGHV4\u201030\u20104<\/jats:italic>\n                      were more often used in all pSS subgroups compared with controls. Memory B cells from SSA\/SSB+ patients displayed a higher proportion of cells with unmutated VDJ transcripts compared with other pSS patient groups and controls, indicating altered somatic hypermutation processes. Comparison with previous studies revealed heterogeneous clonotype pools, with little overlap in CDR3 sequences. Joint analysis using scRNA\u2010seq and scVDJ\u2010seq data allowed unsupervised stratification of patients with pSS and identified novel parameters that correlated to disease manifestations and antibody status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We describe heterogeneity and molecular characteristics in B cells from patients with pSS, providing clues to intrinsic differences in B cells that affect the phenotype and outcome and allowing stratification of patients with pSS at improved resolution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42683","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T09:20:15Z","timestamp":1692782415000},"page":"255-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Multimodal\n         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