| dc.description.abstract | Although many efforts have been done in understanding the aetiology of
rheumatoid arthritis (RA), the Epstein-Barr Virus (EBV) remains one of
the strongest candidates to be investigated as possible environmental
factors in inducing RA. Of relevance, a high percentage of RA patients are
characterised by a strong immune response to EBV, with high blood DNAviral
load and circulating cross-reactive (auto)antibodies reacting against
self-citrullinated antigens (ACPA) and viral proteins.
Due to its lymphotropic behaviour, EBV might be able to rescue an
autoreactive B cell phenotype and thus eludes the immune system
checkpoints. Also, the virus and the infected B cells have been proposed as
a possible source of citrullinated epitopes triggering the disease.
To obtain long-standing EBV-infected B cells, I setup an in vitro co-culture
system whereby RA fibroblasts-like synoviocytes (RA-FLS) obtained from
synovial fluid and synovial tissue of patient were cultured with CD19+B
cells for 28 days. RA-FLS were used as feeding environment for the
CD19+B cells obtained from ACPA+ RA patients and healthy donor. CpG
was added to induce plasmacells differentiation to test the presence of
ACPA antibodies. B cells were then recovered, and analysed trough
fluorescence activated cell sorting (Facs). Finally, molecular biology
analysis has been performed to detect and quantify specific EBV-related
gene such as the BamH1-W repeat region. Also, RA-FLS were recovered
in order to investigate any possible modification induced by the CD19+B
cells in the system.
Preliminary data suggested that the EBV+ CD19+B cells population has a
higher proliferation rate when incubated with RA-FLS, although this is not
exclusive of RA patient since such proliferation was detected also in
healthy donor. Nevertheless, this might reflect an in vivo mechanism in
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which the EBV+ CD19+B cells from the peripheral compartment might
find a preferential proliferating niche in the synovium, due to the RA-FLS.
Furthermore, I am proposing a new method to obtain naturally EBV+ RACD19+
B cells in order to develop a better tool to study the role of the virus
in RA pathogenesis. | en_US |
