The shared epitope and severity of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that frequently leads to skeletal deformity and disability. A significant genetic contribution to the development of RA is widely accepted and estimated to account for approximately 60% of disease risk. 53 To date, the strongest genetic association has been reported with the human leukocyte antigen (HLA) region and, in particular, with HLA-DRB1 alleles that share a similar amino acid sequence. 37 The recognition of this common allele sequence, termed the shared epitope (SE), has provided insight into the genetics of this clinically diverse disease. Although the SE hypothesis was initially proposed to explain genetic susceptibility to RA, subsequent investigation suggests that the primary role of the SE may be in development of more severe disease manifestations. Numerous studies have pursued clarification of this relation; however, there is no definite consensus in the literature. Determination of the precise relationship between the SE and RA severity has profound implications for future patient care and research. The SE may provide prognostic information early in the course of disease for certain subgroups of RA patients or specific outcomes. Clinical trials may benefit with more precise results by identification and randomization of patients according to genetic characteristics. Clarification of the