GENETIC DETERMINATION OF SUSCEPTIBILITY AND SEVERITY IN RHEUMATOID-ARTHRITIS

It is now being increasingly recognized that a significant proportion of persons developing rheumatoid arthritis will relentlessly progress to socio-economic incapacitation and risk a considerably shortened life expectancy. Although a major accomplishment in the last decade was to identify the molecular basis of overall susceptibility to rheumatoid arthritis as the presence of a few particular amino-acid residues on the rim of the major histocompatibility molecule, recent research raises the possibility that severe outcomes of this disease may also be predicted by this structure. Slight variations in the amino acids encoded by these alleles, and, more important, whether one or two such alleles are present, appear to be the determining factors. The article by Weyand and colleagues in this issue of Annals advances our understanding in this area. One anticipates that effective and targeted therapy for severe disease will follow the improved identification of persons most likely to have it develop.