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Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis.

ABSTRACT: Sjögren's syndrome (SjS) is characterized by lymphocytic infiltration of exocrine glands, i.e. autoimmune epithelitis. 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⁺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 naïve B-cell compartments. SjS patients had a higher incidence of EBV-EA-D-IgG⁺ antibodies, characteristic of recent EBV-infection/reactivation. SjS patients with past infection or recent infection/reactivation showed increased CXCR3⁺Th1 and CXCR3⁺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.

SUBMITTER: Barcelos F

PROVIDER: S-EPMC7893064 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis.

Barcelos Filipe F Martins Catarina C Monteiro Ricardo R Cardigos Joana J Prussiani Tiziano T Sítima Miguel M Alves Nuno N Vaz-Patto José J Cunha-Branco Jaime J Borrego Luís-Miguel LM

Scientific reports 20210218 1

Sjögren's syndrome (SjS) is characterized by lymphocytic infiltration of exocrine glands, i.e. autoimmune epithelitis. 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 pr ...[more]

PMID: 33603079

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Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis.

Publications

Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis.

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