INDUCTION OF A SYSTEMIC LUPUS ERYTHEMATOSUS-LIKE DISEASE IN MICE BY A COMMON HUMAN ANTI-DNA IDIOTYPE
INDUCTION OF A SYSTEMIC LUPUS ERYTHEMATOSUS-LIKE DISEASE IN MICE BY A COMMON HUMAN ANTI-DNA IDIOTYPE
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DOI：
10.1073/pnas.85.7.2260
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发表时间：
1988-04-01
影响因子：
11.1
通讯作者：
MOZES, E
中科院分区：
文献类型：
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作者：
MENDLOVIC, S;BROCKE, S;MOZES, E
系统性红斑狼疮（SLE）被认为是典型的自身免疫性疾病。在动物模型中，通过DNA免疫或抗DNA抗体激发诱导SLE尚不可能。我们在此报告了一个SLE样疾病的小鼠模型，通过用常见的人单克隆抗DNA独特型（16/6独特型）免疫C3H.SW雌性小鼠诱导。用16/6独特型加强注射后，在免疫小鼠的血清中检测到高水平的鼠抗16/6和抗抗16/6抗体（与抗DNA活性相关）。观察到与DNA、poly（I）、poly（dT）、核糖核蛋白、自身抗原[Sm、SS-A（Ro）和SS-B（La）]和心磷脂反应的自身抗体滴度升高。血清学检查结果与红细胞沉降率增加、白细胞减少、蛋白尿、肾小球系膜免疫复合物沉积和肾小球硬化有关。肾脏中的免疫复合物显示含有16/6独特型。该实验性SLE样模型可用于阐明SLE的发病机制。
Systemic lupus erythematosus (SLE) is considered to be the quintessential autoimmune disease. It has not been possible to induce SLE in animal models by DNA immunization or by challenge with anti-DNA antibodies. We herewith report a murine model of SLE-like disease induced by immunization of C3H.SW female mice with a common human monoclonal anti-DNA idiotype (16/6 idiotype). Following a booster injection with the 16/6 idiotype, high levels of murine anti-16/6 and anti-anti-16/6 antibodies (associated with anti-DNA activity) were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with DNA, poly(I), poly(dT), ribonucleoprotein, autoantigens [Sm, SS-A (Ro), and SS-B (La)], and cardiolipin were noted. The serological findings were associated with increased erythrocyte sedimentation rate, leukopenia, proteinuria, immune complex deposition in the glomerular mesangium, and sclerosis of the glomeruli. The immune complexes in the kidneys were shown to contain the 16/6 idiotype. This experimental SLE-like model may be used to elucidate the mechanisms underlying SLE.