Non pathogenicity of anthlna and anti-phospholipid antibodies in IVIG preparations

Intravenous immunoglobulins (IVIG) an therapeutic praparations of pooled normal polyspecific immunoglobulin G. We investigated tha presence as well as the in vivo pathogenic potential of eutoantibodies against phospholipids and DNA in several commarcial IVIG preparations. The presence of autoantibodies and their anti-idiotypic antibodies in the IVIG preparations was detected by ELISA. Naive mice were actively immunized with either IVIG preparations or pathogenic monoclonal antibodies against cardiolipin or DNA. Following boost injection the mice were tested for the presence of mouse autoantibodies, and for clinical parameters of the autoimmune condition (erythrocyta sedimentation rate, prolonged aPTT. platelets and white blood cell counts, fetal resorption rate and urinary protein excretion). We found high levels of autoantibodies against a panel of pnospholipids and DNA, including pathogenic idiotypes, as well as their anti-idiotypic activity. In all the IVIG preparations. Following immunization with those IVIG batches, the mice developed high levels of autoantibodies against phospholipids and DNA. similar to mice immunized with pathogenic anti-DNA or anti-cardiolipin Abs. However mice which were immunized with pathogenic anti-cardiolipin (Hz Id⁺) monoclonal Ab had thrombocytopenia, prolonged aPTT and increased fetal resorption rate, while mice immunized with pathogenic anti-DNA (16/6 Id⁺) monoclonal Ab had high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. In contrast, mice immunized with several commercial IVIGs did not develop any of these manifestations. We conclude that commercial IVIG preparations contain high levels of anti-phospholipids and anti-DNA autoantibodies, as well es their anti-idiotypic antibodies. Although these antibodies can induced the generation of mouse autoantibodies, they did not prove to be pathogenic in vivo.