Epstein–Barr virus and rheumatoid arthritis
Section snippets
Genetic factors in RA
HLA-DRB1 alleles containing the QK/RRAA or RRRAA motif in their third hypervariable region (HVR3) carry susceptibility to develop RA [1]. Recently, Reviron et al. [2] have shown that HLA-DRB1 alleles can be classified into three groups: susceptible, like DR4 (except the DRB1*0402 and *0403 subtypes) and DR1, neutral, like DR3 and DR15, protective like DR7, DR8, DRB1*0402.
Epstein–Barr virus (EBV)
The Epstein–Barr virus (EBV or human herpesvirus 4) is a 172-kb double-stranded DNA virus. EBV is carried lifelong. It causes infectious mononucleosis and has been linked to the development of several malignant tumours including Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma and post transplant lymphoproliferative disease. In most people, primary infection and lifelong persistence are asymptomatic [3].
EBV first infects B lymphocytes or epithelial cells of the oropharynx. EBV
Rheumatoid arthritis and EBV
EBV infects almost the entire world adult population and for the past 25 years, a potential role of EBV in the pathogenesis of RA has been suspected.
First, Alspaugh et al. [5] reported that sera from RA patients contained high titers of antibody against a nuclear antigen present in EBV-infected cells. They later confirmed that sera from patients with RA contained high titer antibodies to latent and replicative EBV antigens like Epstein–Barr nuclear antigen (EBNA), viral capsid antigen (VCA),
Conclusions
Decreased T-cell response to gp110, an important EBV replication antigen, might lead to poor control of EBV infection and EBV overload especially in HLA-DRB1*0404 patients [11]. Generally, RA patients have high systemic EBV load and patients with active disease have low cellular response to gp110 [13], [23]. EBV is highly recognized by antibodies but is never eliminated. It is a perfect candidate to cause chronic immune complex disease. Anti-EBV antibody responses in RA patients are the
Take-home messages
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RA patients have higher levels of anti-EBV antibodies than healthy controls.
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EBV-specific suppressor T cell function is defective in RA.
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Patients with RA have a 10-fold higher EBV load than healthy controls.
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EBV is an ideal candidate to trigger chronic immune complex disease in RA.
Acknowledgements
This work was supported by grants from INSERM, Société Française de Rhumatologie (SFR), PHRC 2003.
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Tissue Antigens
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Infectious agents breaking the immunological tolerance: The holy grail in rheumatoid arthritis reconsidered
2022, Autoimmunity ReviewsCitation Excerpt :The crucial problem with these possible infectious players was the capacity to induce an autoimmune disease [9], meaning to break tolerance, to localize to the joints and to satisfy the postulates allowing to define the autoimmune origin of an illness (Witebsky postulates, later modified by Rose and Bona) [10]: 1) an autoimmune reaction is identified in the form of autoantibody or cell-mediated immune reaction, 2) the corresponding Antigen is known, and 3) an analogous response causes a similar disease in experimental animals. EBV has long been recognized as a possible candidate since RA patients have higher levels of anti-EBV antibodies than healthy controls, EBV-specific suppressor T cell function is defective in RA, patients with RA have a 10-fold higher EBV load than healthy controls, thus EBV may be an ideal candidate to trigger chronic immune complex disease in RA [11]. The third Witebsky’ criterion was never satisfied and importantly no evidence of EBV infection using in situ hybridization specific for the EBV-encoded RNAs (EBERs), nor latent membrane protein 1 (LMP1) and lytic-cycle BZLF1 protein were detected by immunohistochemistry in 37 biopsy synovial samples from RA patients [12].
Herpes virus and its manifestations
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