Superantigens and experimental SLE induced by idiotypic dysregulation.
OBJECTIVE
The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the course 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 boost of MIV-7/PBS 3 weeks later, generated an experimental SLE via an idiotypic dysregulation.


RESULTS
After immunization with MIV-7/SAg, replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the regular induction of the SLE-like disease, the mice failed to produce 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 the "classical" protocol showed increased titers of anti-dsDNA Ab (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST-1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respectively.


CONCLUSIONS
These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not induce the SLE-like disease following idiotypic modulation. Moreover, they may have had a suppressive effect on the idiotypic network in our model. The appearance of anti-CL Abs in almost all the experimental groups including the naive mice supports the possibility that microbial SAgs can induce the production of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and 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.
Baharav
E
E
Department of Medicine B, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel.
Gur
H
H
Fishman
P
P
Ziporen
L
L
Blank
M
M
Aelion
J
J
Kotb
M
M
Shoenfeld
Y
Y
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000096:biosynthesis; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000941:Antigens; D000942:Antigens, Bacterial; D001323:Autoantibodies / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology; D001427:Bacterial Toxins; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D007117:Immunization, Secondary; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000276:immunology; D011506:Proteins; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D000941:Antigens; D000942:Antigens, Bacterial; D001323:Autoantibodies; D001427:Bacterial Toxins; D004768:Enterotoxins; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal; D005620:Freund's Adjuvant