ANTI-DNA AND ANTIPHOSPHOLIPID ANTIBODIES IN IVIG PREPARATIONS - IN-VIVO STUDY IN NAIVE MICE

Intravenous immunoglobulins (MG) are therapeutic preparations of poole d normal polyspecific immunoglobulin G. We investigated the presence a nd the bz vivo pathogenic potential of autoantibodies against phosphol ipids and DNA in several commercial IVIG preparations. The presence of autoantibodies and their antiidiotypic antibodies in the IVIG prepara tions was detected by ELISA, Naive mice were actively immunized with e ither IVIG preparations or pathogenic monoclonal antibodies (mAbs) aga inst cardiolipin (CL) or DNA, in an attempt to induce autoimmune condi tions. The mice were tested for the presence of mouse autoantibodies ( auto-Abs) and for clinical parameters of autoimmune diseases. We found high levels of auto-Abs against a panel of phospholipids and DNA, as well as their antiidiotypic Abs, in all the IVIGs. Affinity studies po inted to a lower affinity of auto-Abs of IVIG origin to their respecti ve antigens compared to pathogenic mAbs. Mice immunized with pathogeni c anti-CL mAb had high levels of antiphospholipid auto-abs, accompanie d by thrombocytopenia, prolonged aPTT, and an increased fetal resorpti on rate. Mice immunized with pathogenic anti-DNA mAb had elevated anti -DNA and anti-CL auto-Abs, along with a high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. Following immunization with IgGs from IVIG batches, mice developed high levels of auto-Abs a gainst phospholipids and DNA, similar to mice immunized with pathogeni c anti-DNA or anti-CL mAbs, but none of the mice expressed the clinica l manifestations compatible with the presence of these autoantibodies. We conclude that commercial IVIG preparations contain high levels of antiphospholipid and anti-DNA auto-Abs, as well as their antiidiotypic Abs. Although these Abs induced the generation of mouse auto-abs upon active immunization, following idiotypic manipulation they did not pr ove to be pathogenic in vivo.