Excitement—and Confusion—about HLA and Rheumatoid Arthritis

rvheumatoid arthritis has successfully resisted the efforts of many investigators to find a specific cause of the dis-ease or a single genetic basis for risk. Vigorous debate continues about whether a retrovirus from the environ-ment, an autoantigen from a patient's connective tissues, or plasma, or a cross-reactive immune response between host tissues and a superantigen (for example, bacterial heat shock proteins) triggers this disease. Except for a person's recognized high risk for developing rheumatoid arthritis when she or he has an identical twin with the disease (1), there was little evidence for a genetic predis-position until Astorga and Williams (2) reported in 1969 that in 14 of 22 different patients with rheumatoid arthri-tis, lymphocytes mixed in cultures did not activate each other. These data, which in retrospect implied identica