SUPERANTIGENS AND EXPERIMENTAL SLE INDUCED BY IDIOTYPIC DYSREGULATION

Objective. The effects of the superantigens (SAgs) Staphylococcal Ente rotoxin B (SEE), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the co urse of experimental SLE-like disease. Methods. Immunization of BALB/c mice with human anti-DNA mAb (MIV-7) carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant (CFA), followed by a bo ost of MIV-7/PBS 3 weeks Inter, generated nn experimental SLE via an i diotypic dysregulation. Results. After immunization with MIV-7/SAg, re placing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after t he regular induction of the SLE-like disease, the mice failed to produ ce anti-hIgM and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV-7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in 25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice immunized with non- pathogenic human IgM/SAg or PBS/SAg. The mice immunized according to t he ''classical'' protocol showed increased titers of anti-dsDNA Ab (22 %) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SE E, TSST-1 and MAIM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respec tively. Conclusion. These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral res ponse. The SAgs TSST-1, SEE and MAM did not induce the SLE-like diseas e following idiotypic modulation Moreover, they may have had a suppres sive effect on the idiotypic network in our model. The appearance of a nti-CLAbs in almost all the experimental groups including the naive mi ce supports the possibility that microbial SAgs can induce the product ion of autoantibodies by different mechanisms. The SAgs TSST-1, SEE an d MAM reduced autoantibody production in the serologically established idiotypic-induced experimental SLE-like murine model. This beneficial effect may indicate new directions for research on the management of SLE.