ABROGATION OF EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS 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 experim ental 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 wer e carried out: autoantibody profile (ELISA), clinical manifestations i ncluding erythrocyte sedimentation rate (ESR), white blood cell and pl atelet count, immunoglobulin deposits in the kidneys, and fetal resorp tions. The presence of antiidiotypic activity to anti-DNA and aCL anti bodies 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 an d leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated pa rtial 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 presen ce of antiidiotypic activity to anti-dsDNA and aCL antibodies in the I VGG 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 idioty pic network and neutralization of the pathogenic autoantibodies. Our r esults may justify the use of IVGG in patients with SLE and/or APS.