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Lymphocytes are central in SjS pathogenesis, with B-cell hyperactivity mediated by T-cells. B-cells are main targets of Epstein-Barr virus (EBV) infection, a frequently-suggested trigger for SjS. We aimed to evaluate how the EBV infection modulates B and T-cell subsets in SjS, including as controls Rheumatoid arthritis patients (RA) and healthy participants (HC). SjS patients presented decreased CXCR5\n                    <jats:sup>+<\/jats:sup>\n                    T-cells, although IL21-secreting Tfh and Tfc cells were increased. Tfc were positively correlated with ESSDAI scores, suggesting their relevant role in SjS pathogenesis. As previously described, SjS patients showed expanded circulating na\u00efve B-cell compartments. SjS patients had a higher incidence of EBV-EA-D-IgG\n                    <jats:sup>+<\/jats:sup>\n                    antibodies, characteristic of recent EBV-infection\/reactivation. SjS patients with past infection or recent infection\/reactivation showed increased CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    Th1 and CXCR3\n                    <jats:sup>+<\/jats:sup>\n                    Tfh1 cells compared to those without active infection. SjS patients with a recent infection\/reactivation profile presented increased transitional B-cells compared to patients with past infection and increased plasmablasts, compared to those without infection. Our results suggest EBV-infection contributes to B and T-cell differentiation towards the effector phenotypes typical of SjS. Local lymphocyte activation at ectopic germinal centres, mediated by Tfh and Tfc, can be EBV-driven, perpetuating autoimmune epithelitis, which leads to gland destruction in SjS.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-83550-0","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T04:14:59Z","timestamp":1613794499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-0808","authenticated-orcid":false,"given":"Filipe","family":"Barcelos","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-0421","authenticated-orcid":false,"given":"Catarina","family":"Martins","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7586-5290","authenticated-orcid":false,"given":"Ricardo","family":"Monteiro","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9053-0720","authenticated-orcid":false,"given":"Joana","family":"Cardigos","sequence":"additional","affiliation":[]},{"given":"Tiziano","family":"Prussiani","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-3924","authenticated-orcid":false,"given":"Miguel","family":"S\u00edtima","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-1032","authenticated-orcid":false,"given":"Nuno","family":"Alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-4742","authenticated-orcid":false,"given":"Jos\u00e9","family":"Vaz-Patto","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7024-4375","authenticated-orcid":false,"given":"Jaime","family":"Cunha-Branco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-438X","authenticated-orcid":false,"given":"Lu\u00eds-Miguel","family":"Borrego","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,2,18]]},"reference":[{"key":"83550_CR1","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1097\/BOR.0000000000000473","volume":"30","author":"E Pontarini","year":"2018","unstructured":"Pontarini, E., Lucchesi, D. & Bombardieri, M. 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