IMMUNOCHEMICAL CHARACTERIZATION OF ANTI-RNA ANTIBODIES FOUND IN SCLERODERMA AND SYSTEMIC LUPUS-ERYTHEMATOSUS .2. REACTIVITY WITH HSA-COUPLED, URIDINE-CONTAINING, MONOPHOSPHORIC RIBODINUCLEOTIDES

Abstract

Sera from patients with scleroderma were found to have anti-RNA antibodies which react with human serum albumin (HSA)-coupled uridine and UMP and are inhibited by uracil, uridine and UMP. Scleroderma sera react uniformly with 5''-polyuridylic acid (poly(U)) and fail to react with polyadenylic, polyuridylic acid (poly(A).cntdot.poly(U)) which is also indicative of their uracil specificity. Anti-RNA antibodies found in systemic lupus erythematosus (SLE) are immunochemically different from those found in scleroderma in that, instead of being uniformly specific to uracil, they are markedly heterogeneous and may react with uracil, uridine and/or UMP. SLE sera frequently react with poly(A).cntdot.poly(U), indicating also their ability to recognize the double helical structure of double-stranded RNA. Thirty-seven scleroderma and 34 SLE sera from as many patients with either of these conditions were tested against HSA-coupled, uridine-containing monophosphoric dinucleotides in an attempt to characterize further their anti-RNA antibodies. Scleroderma sera reacted primarily with dinucleotides in which uridine was the base proximal to the carrier protein and, except for sera that also contained antibodies to adenosine which reacted with UpA, they failed to react with dinucleotides in which uridine was in a terminal position only. Reaction with dinucleotides in which uridine was proximal to the carrier protein could be inhibited by uracil but not by the corresponding terminal base. Some lupus sera reacted with both dinucleotides that contain the same bases in opposite sequence, e.g., ApU and UpA, while others reacted with only 1 of the sequences. They also reacted more frequently with dinucleotides in which HSA was coupled to a base other than uridine, suggesting that the reaction is primarily due to anti-DNA antibodies. Because immunization with dinucleotides coupled to protein prepared by the method used yields higher specificity to the base attached to the carrier protein, the findings suggest that, in scleroderma, a single event, akin to that of immunization with a purified antigen, gives rise to the anti-RNA antibodies, whereas in SLE there is a considerably wider immunological aberration.