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The cause of rheumatoid arthritis (RA) still eludes us, though we know from twin studies that both genetic and environmental factors are important contributory components to disease susceptibility1; the latter is estimated to account for about one half of this risk.2 At least one major RA susceptibility gene resides within the major histocompatibility complex (MHC) region. Current dogma is that this is explained by a conserved sequence of amino acids within the third hypervariable region of the DRB1 β chain molecule encoded by a number of alleles. This is usually referred to as being the RA shared epitope hypothesis.3Although DRB1 molecules present peptide fragments to T cell receptors on CD4 positive lymphocytes, the exact mechanism through which the RA shared epitope exerts its effect remains unclear.4 Given that class II molecules such as DRB1 serve an immunoregulatory role, it is not surprising that polymorphisms within these structures will influence variation in immune response in both health and disease states. It is likely that the RA shared epitope conveys disease susceptibility through its interaction with the environment. Characterising such interactions will be fundamental to our understanding of RA aetiopathogenesis.
A specific environmental/infectious trigger(s) for RA has yet to be identified, though there has been no shortage of contenders for this role, including mycoplasmas, parvovirus B19, cytomegalovirus, herpes virus 6, and Epstein-Barr virus (EBV).5-7 The involvement of EBV in RA has been investigated and speculated about for over 15 years. Although definite proof is lacking, an increasing body of circumstantial evidence points at a close relation between the two. This evidence has been added to by the study conducted by Toussirot and colleagues (presented in this issue, p 533). These workers show that patients with RA have decreased T cell precursor frequencies to EBV gp110 …
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