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 frequentl...

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Autores principales:	Filipe Barcelos, Catarina Martins, Ricardo Monteiro, Joana Cardigos, Tiziano Prussiani, Miguel Sítima, Nuno Alves, José Vaz-Patto, Jaime Cunha-Branco, Luís-Miguel Borrego
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/902c985bed3e4bf1b88afc01f885ec33
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spelling	oai:doaj.org-article:902c985bed3e4bf1b88afc01f885ec332021-12-02T12:11:50ZAssociation between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis10.1038/s41598-021-83550-02045-2322https://doaj.org/article/902c985bed3e4bf1b88afc01f885ec332021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83550-0https://doaj.org/toc/2045-2322Abstract 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.Filipe BarcelosCatarina MartinsRicardo MonteiroJoana CardigosTiziano PrussianiMiguel SítimaNuno AlvesJosé Vaz-PattoJaime Cunha-BrancoLuís-Miguel BorregoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Filipe Barcelos Catarina Martins Ricardo Monteiro Joana Cardigos Tiziano Prussiani Miguel Sítima Nuno Alves José Vaz-Patto Jaime Cunha-Branco Luís-Miguel Borrego Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
description	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.
format	article
author	Filipe Barcelos Catarina Martins Ricardo Monteiro Joana Cardigos Tiziano Prussiani Miguel Sítima Nuno Alves José Vaz-Patto Jaime Cunha-Branco Luís-Miguel Borrego
author_facet	Filipe Barcelos Catarina Martins Ricardo Monteiro Joana Cardigos Tiziano Prussiani Miguel Sítima Nuno Alves José Vaz-Patto Jaime Cunha-Branco Luís-Miguel Borrego
author_sort	Filipe Barcelos
title	Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
title_short	Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
title_full	Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
title_fullStr	Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
title_full_unstemmed	Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis
title_sort	association between ebv serological patterns and lymphocytic profile of sjs patients support a virally triggered autoimmune epithelitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/902c985bed3e4bf1b88afc01f885ec33
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Association between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitis

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