Association between the TNFRII 196R allele and diagnosis of rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease, and it can lead to progressive joint destruction, deformity and severe disability. Early diagnosis of RA and timely initiation of disease-modifying antirheumatic drugs (DMARDs) are necessary to limit joint damage and optimise the functional outcome (i.e. the concept of a 'window of opportunity') [1,2]. No diagnosis criteria for RA are yet available, the 1987 American College of Rheumatology (ACR) criteria being classification criteria [3]. With the overall objective being to manage patients better, identification of markers that would allow one to establish a diagnosis of RA at the very beginning of the disease process remains an important goal. Certain autoantibodies have been reported to be specific for RA [4] and thus may help in the diagnosis of RA. Autoantibodies against cyclic citrullinated peptides (anti-CCP) are specific for RA but lack sensitivity; this contrasts with rheumatoid factor, which has strong sensitivity but low specificity for RA. Recently, a study conducted in blood donors [5] showed that positivity for IgM rheumatoid factor and anti-CCP may precede the clinical manifestations of RA. However, although concomitant positivity of both markers has been shown to be highly predictive of a diagnosis of RA, it has a low sensitivity (<50%) [6,7]. Thus, new RA diagnosis markers are needed, such as autoantibody populations and/or genetic markers. The latter have the particular advantages of being present from the onset of the disease and of remaining unchanged by therapy. To date, the only genetic susceptibility factor identified for RA is HLA-DRB1. This association is restricted to HLA-DRB1 alleles encoding a specific conserved amino acid sequence referred to as the shared epitope [8]. The predictive value of the shared epitope alleles for diagnosis of RA was studied in a cohort of 680 patients with early unclassified arthritis and was found to be lower than expected [9]. Th