HLA and rheumatoid arthritis
Many studies have described the strong association between certain subtypes of HLA-DR4/DR1 and rheumatoid arthritis. By comparing the sequences of the various RA-related alleles, it has been observed that a five amino acid stretch, QK/RRAA, is common among all HLA alleles correlated to rheumatoid arthritis (Table 3). The QKRAA sequence was called
'shared epitope', with the idea that it may be involved in the ctiopathogenesis of rheumatoid arthritis (Figure 1). Interestingly, the 'shared epitope' seems to be influencing susceptibility to rheumatoid arthritis and also the severity and the outcome of the disease. Together, these observations show that HLA genes play an important role in the etiopathogenesis of rheumatoid arthritis, probably by providing a sort of 'prearthritic' immunological background on which the triggering factors may thrive.
Recognition of an antigen presented by the HLA molecule is mediated by the T cell receptor (TCR). The genes encoding the a/(3 receptor consist of variable (V), diversity (D), joining (J) and constant (C) regions. During T cell development, germline genes encoding one for each V, D, J, C region rearrange to form the functional gene. The preferential usage of some of these combinations in rheumatoid arthritis may be related to recognition of a specific autoanti-
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