Baharav E, Gur H, Fishman P, Ziporen L, Blank M, Aelion J, Kotb M, Shoenfeld Y
Department of Medicine B, Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Israel.
Clin Exp Rheumatol. 1996 Jul-Aug;14(4):359-66.
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.
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.
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.
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.
研究超抗原（SAgs）葡萄球菌肠毒素B（SEB）、中毒性休克综合征毒素-1（TSST-1）和关节炎支原体丝裂原（MAM）对实验性系统性红斑狼疮（SLE）样疾病诱导及病程的影响。
用携带致病性独特型16/6的人抗DNA单克隆抗体（MIV-7）与完全弗氏佐剂（CFA）乳化后免疫BALB/c小鼠，3周后用MIV-7/磷酸盐缓冲液（PBS）加强免疫，通过独特型失调引发实验性SLE。
用MIV-7/SAgs免疫后，用SAgs替代MIV-7加强免疫，然后在常规诱导SLE样疾病7周后注射SAgs，小鼠在诱导后长达6个月未能产生抗人IgM和双链DNA抗体（dsDNA Ab）。用MIV-7/CFA免疫并用SAgs加强免疫的小鼠有高滴度的抗人IgM，但未检测到抗dsDNA Ab。在两个实验组中，分别有25/40（62%）和30/38（79%）的小鼠产生了低滴度的抗心磷脂抗体（anti-CL Abs），包括用非致病性人IgM/SAgs或PBS/SAgs免疫的对照小鼠。按照“经典”方案免疫的小鼠在10周观察期内抗dsDNA Ab（22%）和抗CL Ab（28%）滴度升高。相比之下，SEB、TSST-1和MAM分别使抗DNA滴度降低29%、1%和17%，抗CL滴度降低3%、15%和12%。
这些数据表明，此处测试的SAgs不能替代CFA在诱导初次体液反应中的作用。SAgs TSST-1、SEB和MAM在独特型调节后未诱发SLE样疾病。此外，它们可能对我们模型中的独特型网络有抑制作用。几乎所有实验组包括未免疫小鼠中都出现抗CL Abs，这支持微生物SAgs可通过不同机制诱导自身抗体产生的可能性。SAgs TSST-1、SEB和MAM在血清学建立的独特型诱导实验性SLE样小鼠模型中减少了自身抗体的产生。这种有益作用可能为SLE治疗研究指明新方向。
