Abrogation of experimental systemic lupus erythromatosus and primary antiphospholipid syndrome with intravenous gamma globulin

Objective. To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). Methods. BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')₂, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')₂ as inhibitor. Results. Following treatment with IVGG or IVGG F(ab')₂, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDNA and aCL antibodies in the IVGG preparation. Conclusion. Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of the pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.