{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T12:53:02Z","timestamp":1784119982572,"version":"3.55.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Primary Sj\u00f6gren\u2019s syndrome (pSS) is a highly heterogeneous autoimmune disease. Previous studies have suggested that rheumatoid factor (RF)-positive patients appear to have a higher incidence of systemic involvement. However, the underlying mechanisms remain unclear. This study aims to elucidate the potential biological mechanisms through single-cell RNA sequencing (scRNA-seq).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Peripheral blood mononuclear cells from 3 healthy controls, 6 RF-negative (RF\n                      <jats:sup>-<\/jats:sup>\n                      ) pSS patients, and 6 RF-positive (RF\n                      <jats:sup>+<\/jats:sup>\n                      ) pSS patients were subjected to scRNA-seq. Subsequent analyses included pathway enrichment analysis, trajectory analysis, cell-cell communication analysis, and B cell receptor (BCR) and T cell receptor (TCR) repertoire profiling. Potential differences were further validated by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of B cell subsets revealed a significantly increased proportion of plasma cells in RF\n                      <jats:sup>+<\/jats:sup>\n                      patients, and differential gene expression analysis indicated enhanced pathways related to antibody production, clonal expansion, and type I interferon activation. In T-cell subsets, the RF\n                      <jats:sup>+<\/jats:sup>\n                      group showed a notably higher proportion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, which exhibited stronger cytotoxicity and activation of interferon signaling. In contrast, mucosal-associated invariant T (MAIT) cells demonstrated activated interferon signaling but were present at a lower proportion compared to the RF\n                      <jats:sup>-<\/jats:sup>\n                      group. Cell\u2013cell communication analysis revealed strengthened crosstalk between B cells and T cells in the RF\n                      <jats:sup>+<\/jats:sup>\n                      group. Pseudo-time trajectory analysis further indicated that in RF\n                      <jats:sup>+<\/jats:sup>\n                      patients, both plasma cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells exhibited a developmental skew toward a terminally differentiated state. Additionally, both BCR and TCR repertoire analyses indicated RF\n                      <jats:sup>+<\/jats:sup>\n                      and RF\n                      <jats:sup>-<\/jats:sup>\n                      patients exhibiting distinct patterns in clonal distribution and frequency. Flow cytometry further validated the increased proportion of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and the decreased proportion of MAIT cells in the peripheral blood of RF\n                      <jats:sup>+<\/jats:sup>\n                      pSS patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The RF status in pSS patients is closely associated with specific immune cell profiles. RF\n                      <jats:sup>+<\/jats:sup>\n                      patients exhibit more active plasma cell responses, enhanced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell cytotoxicity and interferon responses, as well as heightened interferon signaling yet reduced proportion of MAIT cells. RF status serves as a key stratification marker for immune heterogeneity in pSS patients, providing new insights for understanding disease mechanisms and developing targeted therapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1822615","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:47:32Z","timestamp":1781156852000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunological profiling of rheumatoid factor-positive primary Sj\u00f6gren\u2019s syndrome by single-cell RNA sequencing"],"prefix":"10.3389","volume":"17","author":[{"given":"Yifei","family":"Wang","sequence":"first","affiliation":[{"name":"Dongzhimen Hospital, Beijing University of Chinese Medicine","place":["Beijing, China"]},{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Ji","sequence":"additional","affiliation":[{"name":"Qihuang School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Teng","sequence":"additional","affiliation":[{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Han","sequence":"additional","affiliation":[{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Zhi","sequence":"additional","affiliation":[{"name":"Graduate School, Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwen","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine (TCM) Rheumatology, China-Japan Friendship Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine (TCM) Rheumatology, China-Japan Friendship Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13075-024-03262-4","article-title":"Manifestations and management of Sj\u00f6gren's disease","volume":"26","author":"Maleki-Fischbach","year":"2024","journal-title":"Arthritis Res Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01135-3","article-title":"Update on the pathophysiology and treatment of primary Sj\u00f6gren syndrome","volume":"20","author":"Baldini","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s2665-9913(24)00039-0","article-title":"Precision medicine in Sj\u00f6gren's disease","volume":"6","author":"Gandolfo","year":"2024","journal-title":"Lancet Rheumatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-023-01057-6","article-title":"Epidemiology of sj\u00f6gren syndrome","volume":"20","author":"Beydon","year":"2024","journal-title":"Nat Rev Rheumatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26104797","article-title":"Additive value of rheumatoid factor isotypes in Sj\u00f6gren's syndrome patients with joint complaints of different etiologies-can rheumatoid factor IgA serve as an early, poor prognostic biomarker candidate","volume":"26","author":"Aradi","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/ard.43.5.673","article-title":"Prospective study of early rheumatoid arthritis. 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