Objective. The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression.

Methods. Autoantibodies to Ro/SS-A, La/SS-B, U1 RNP, and Sm were measured by quantitative enzyme-linked immunosorbent assay using affinity-purified antigens.

Results. Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti—RNA proteins (e.g., Ro/SS-A, La/SS-B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti—RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (± 1.05 SD) anti—RNA proteins, while the control SLE pairs shared only 0.33 (± 0.82), P < 0.01 (t = 4.0, P < 0.01). In addition, in the white SLE twins, all had elevated levels of anti—U1 RNP while in white nontwin SLE patients, the frequency of anti—U1 RNP was 30%.

Conclusion. These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.