{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:19Z","timestamp":1784700379892,"version":"3.55.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>Background<\/jats:title>\n                    <jats:p>Sj\u00f6gren\u2019s disease (SjD) is a systemic autoimmune disease showing clinical characteristics similar to systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) at early phases, complicating diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study, blood was obtained from 65 SjD, 34 SLE, and 44 SSc patients and 56 healthy donors (HD). Numbers and percentage of circulating leukocytes and expression of HLA-DR, PSGL-1, ADAM8, IL-10 and IFN\u03b1 were determined by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to HD, SjD patients showed generalized immune system activation and global reduction of circulating leukocytes, except for plasma cells, which were increased. IFN\u03b1 levels were reduced in SjD CD16- monocytes, dendritic cells (DC), B cells and basophils, but increased in SjD CD16\n                      <jats:sup>+<\/jats:sup>\n                      monocytes and T cells, showing a positive correlation between IFN\u03b1 T cell levels and percentage of circulating plasma cells. ADAM8 expression levels were reduced in CD16+ monocytes and B cells. In plasma cells and plasmablasts reduction of ADAM8 expression levels were observed during disease activity. SjD patients had reduced percentage of PSGL-1\n                      <jats:sup>+<\/jats:sup>\n                      neutrophils and increased percentage of PSGL-1\n                      <jats:sup>+<\/jats:sup>\n                      B cells (PS1B), which expressed higher levels of IL-10 than those from HD. Low percentage of PSGL-1-expressing neutrophils, basophils, T cells and NK cells and low PSGL-1 expression level in pDC associated with the presence of cutaneous manifestations. Low PSGL-1 expression level in basophils, cDC and both CD16\n                      <jats:sup>-<\/jats:sup>\n                      and CD16\n                      <jats:sup>+<\/jats:sup>\n                      monocytes was associated with the presence of anti-SSB autoantibodies. Remarkably, we found two cellular biomarkers: PS1B\/%pDC ratio (PPr) distinguished SjD patients from HD (accuracy: 78%) and from SSc (accuracy: 84%) and PS1B discriminated SjD from SLE (accuracy: 70%). Both biomarkers improved diagnostic accuracy when combined with current serological markers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dysregulated PSGL-1 and ADAM8 expression in SjD circulating cells is associated with important clinical manifestations in SjD patients, supporting their potential relevance as therapeutic targets in this disease. Additionally, we found PS1B and PPr as new cellular biomarkers that could help improve SjD diagnostic accuracy, particularly in seronegative or ambiguous cases during the early phase of disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1848689","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:03Z","timestamp":1784699523000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dysregulated expression of PSGL-1 and ADAM8 in Sj\u00f6gren\u2019s disease: potential contribution to disease pathogenesis"],"prefix":"10.3389","volume":"17","author":[{"given":"Alejandra","family":"Ramos-Manzano","sequence":"first","affiliation":[{"name":"Immunology Department, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica (FIB)-Hospital Universitario de La Princesa, Instituto de Investigaci\u00f3n Sanitaria (IIS)-Princesa","place":["Madrid, 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