Induction of experimental anti-phospholipid syndrome associated with SLE following immunization with human monoclonal pathogenic anti-DNA idiotype.

MIV-7 is a human monoclonal antibody that binds to DNA and carries a pathogenic anti-DNA idiotype 16/6. The antibody was generated by fusing peripheral blood lymphocytes of a healthy donor which were stimulated with an anti-idiotypic antibody to B11 (a human mAb anti-mouse mammary tumor virus-MMTV). The MIV-7, in addition to being an anti-DNA antibody, also binds to MMTV glycoproteins. Following immunization into the footpad of naive BALB/c mice with MIV-7, the mice developed anti-phospholipid syndrome (APLS) and SLE. The APLS was characterized by thrombocytopenia, the presence of anticardiolipin antibodies, lupus anticoagulant (prolonged APTT), high resorption rate of fetuses and lower mean weights of the placentae and fetuses. The SLE was characterized by serological markers (e.g. anti-DNA), laboratory (increased sedimentation rate and proteinuria) and histological findings (deposition of immune complexes in the glomeruli). Active immunization of mice with mouse monoclonal anti-cardiolipin antibodies led to the induction of primary APLS without SLE. The results add to our previous passive transfer model in which mouse monoclonal anti-cardiolipin antibody generated from immunized mice (CAM) was infused into the tail vein and also resulted in induction of pure APLS [11]. Our results demonstrate the ability to induce secondary APLS to SLE following immunization with a pathogenic idiotype of anti-DNA antibodies and to induce primary APLS with anti-cardiolipin mAb. The existence of these experimental models may permit controlled studies of novel therapeutic models.