Some autoantibodies to Ro/SS-A and La/SS-B are antiidiotypes to anti-double-stranded DNA

Abstract

Objective. To determine the relationship of anti-Ro/SS-A and anti-La/SS-B antibodies to anti-double-stranded DNA (anti-dsDNA) in sera from patients with systemic lupus erythematosus. Methods. Sera with anti-Ro/SS-A alone (n = 5) or those with anti-Ro/SS-A and anti-La/SS-B (n = 7) were absorbed with purified Ro/SS-A and La/SS-B, respectively. The absorbed sera were then tested for reactivity with MOLT-4 extract by Western blot and dsDNA by enzyme-linked immunosorbent assay (ELISA). With selected sera, anti-dsDNA was isolated on DNA cellulose columns and anti-Ro/SS-A and anti-La/SS-B were isolated on antigen-affinity columns. Reactivity between anti-dsDNA and autologous anti-Ro/ SS-A or anti-La/SS-B, as well as inhibition by cognate antigens, was studied. Results. After absorption, all sera showed reactivity with small nuclear RNP A and D bands in Western blots, and some showed reactivity with dsDNA by ELISA. Anti-dsDNA populations (n = 4) were purified on dsDNA cellulose columns. Anti-Ro/SS-A (n = 1) and anti-La/SS-B (n = 3) were affinity purified from the same sera as the anti-dsDNA. In all cases, anti-dsDNA bound autologous anti-Ro/SS-A and anti-La/SS-B much more strongly than it bound normal pooled IgG. Moreover, dsDNA, but not RNA, blocked these interactions. In addition, Ro/SS-A blocked anti-Ro/SS-A and La/ SS-B blocked anti-La/SS-B in these same interactions. Conclusion. In sera with anti-Ro/SS-A and anti-La/SS-B, there are subpopulations of these antibodies that bind and mask anti-dsDNA. We hypothesize that these anti-Ro/SS-A and anti-La/SS-B antibodies are anti-idiotypes to idiotypes on anti-dsDNA and that they both mask and down-regulate these anti-dsDNA antibodies.