• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    Ectopic lymphoid structures support Epstein-Barr virus persistence and autoreactive plasma cell infection in Rheumatoid Arthritis synovium and Sjogren’s Syndrome salivary glands 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • Ectopic lymphoid structures support Epstein-Barr virus persistence and autoreactive plasma cell infection in Rheumatoid Arthritis synovium and Sjogren’s Syndrome salivary glands
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • Ectopic lymphoid structures support Epstein-Barr virus persistence and autoreactive plasma cell infection in Rheumatoid Arthritis synovium and Sjogren’s Syndrome salivary glands
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Ectopic lymphoid structures support Epstein-Barr virus persistence and autoreactive plasma cell infection in Rheumatoid Arthritis synovium and Sjogren’s Syndrome salivary glands

    View/Open
    C Croia PhD.pdf (4.912Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    The ubiquitous ɣ-herpesvirus Epstein-Barr virus (EBV) infects B cells and modifies their differentiation programme leading to B cell activation and immortalization. Although different evidences support a link between EBV infection and rheumatoid arthritis (RA) and Sjogren’s syndrome (SS), the exact role of EBV in RA and SS pathogenesis remain elusive. Recently ectopic lymphoid structures (ELS) have been identified as preferential niches for EBV persistence and reactivation in patients with multiple sclerosis and myasthenia gravis. Independent studies demonstrated that around 50% of RA synovia and 30% of SS salivary glands are characterised by the development of functional ELS, capable to promote local differentiation of autoreactive plasma cells. In this PhD project I explored the potential role of EBV in RA and SS pathogenesis by analysing EBV infection in the RA synovium and SS salivary glands and its relationship with ELS, in situ autoreactive plasma cell differentiation, pathogenic autoantibodies production and cytotoxic immune response. In this work I demonstrated that: i) markers of EBV latent and lytic infection are consistently associated with the presence of ELS in the RA synovium and SS salivary glands; ii) latent EBV proteins are preferentially expressed by B cells, while viral reactivation occurs in plasma cells; iii) a large subset of autoreactive plasma cells is EBV lytically infected in the RA synovia and SS salivary glands; iv) antibodies specific for unmodified and citrullinated EBV peptides, known to cross-recognize ACPA, are produced within ectopic lymphoid structures as 8 demonstrated in vivo in human RA/SCID chimeras; v) SS salivary gland grafts transplanted into SCID mice release human IgG against EBV antigens, whose production correlates with the level of SS-associated auto-antibodies and vi) analysis of CD8+ and CD4+ T-cell localization and granzyme B expression indicated that EBV persistence in ELS-containing RA synovia and SS salivary glands may be favoured by exclusion of CD8+ T cells from B-cell follicles and impaired CD8-mediated cytotoxicity. Overall, these results redefine a novel and pathogenically relevant role for EBV in B-cell dysregulation and chronic inflammation in RA synovium and SS salivary glands.
    Authors
    Croia, Cristina
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/8732
    Collections
    • Theses [3321]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.