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

2021-02-18Artigo científico Acesso aberto
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dc.contributor.authorBarcelos, Filipe
dc.contributor.authorBarcelos, Filipe
dc.contributor.authorMartins, Catarina
dc.contributor.authorMartins, Catarina
dc.contributor.authorMonteiro, Ricardo
dc.contributor.authorCardigos, Joana
dc.contributor.authorPrussiani, Tiziano
dc.contributor.authorSítima, Miguel
dc.contributor.authorAlves, Nuno
dc.contributor.authorVaz-Patto, José
dc.contributor.authorBranco, Jaime
dc.contributor.authorBranco, Jaime
dc.contributor.authorBorrego, Luís-Miguel
dc.contributor.authorBORREGO, LUIS MIGUEL
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - pólo NMS
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblNature Publishing Group
dc.date.accessioned2021-02-23T00:04:09Z
dc.date.available2021-02-23T00:04:09Z
dc.date.issued2021-02-18
dc.description.abstractSjögren'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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1325147
dc.identifier.doi10.1038/s41598-021-83550-0
dc.identifier.issn2045-2322
dc.identifier.otherPURE: 28243767
dc.identifier.otherPURE UUID: acf714ac-c9cc-42ca-af04-696a6d7297ca
dc.identifier.otherPubMed: 33603079
dc.identifier.otherORCID: /0000-0003-4708-438X/work/89320213
dc.identifier.otherORCID: /0000-0003-0353-0421/work/89320468
dc.identifier.otherScopus: 85101209751
dc.identifier.otherWOS: 000621412400037
dc.identifier.urihttp://hdl.handle.net/10362/112280
dc.language.isoeng
dc.peerreviewedyes
dc.titleAssociation between EBV serological patterns and lymphocytic profile of SjS patients support a virally triggered autoimmune epithelitisen
dc.typejournal article
degois.publication.firstPage
degois.publication.issue1
degois.publication.lastPage
degois.publication.titleScientific Reports
degois.publication.volume11
dspace.entity.typePublication
person.familyNameBarcelos
person.familyNameMartins
person.familyNameBranco
person.familyNameBORREGO
person.givenNameFilipe
person.givenNameCatarina
person.givenNameJaime
person.givenNameLUIS MIGUEL
person.identifier.ciencia-idB612-E5C3-60DC
person.identifier.ciencia-id4119-915F-EF0F
person.identifier.orcid0000-0002-3764-0808
person.identifier.orcid0000-0003-0353-0421
person.identifier.orcid0000-0001-7024-4375
person.identifier.orcid0000-0003-4708-438X
person.identifier.scopus-author-id8417815400
person.identifier.scopus-author-id8346933500
rcaap.rightsopenAccess
relation.isAuthorOfPublicationf74be637-6f68-4297-9620-e6ef2356afc9
relation.isAuthorOfPublicationfbfcc667-a22a-43f0-8573-e6652fd04eb5
relation.isAuthorOfPublication4caea9f3-40dd-4c95-98ec-0120509287c0
relation.isAuthorOfPublication027a8b74-0ce7-4daa-9ef4-917b9ec6f95a
relation.isAuthorOfPublication.latestForDiscovery4caea9f3-40dd-4c95-98ec-0120509287c0

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