The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

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Abstract
Natural immunoglobulin G (IgG) autoantibodies are present in the plasma of healthy individuals and, as a result, in pooled therapeutic intravenous immunoglobulin (IVIg) preparations. The production processes of commercial IVIg preparations involve different fractionation and virus‐inactivation steps that include in some cases treatments at extreme conditions. Different physical and chemical treatments are known to augment greatly the reactivity of natural autoantibodies to self‐antigens. It is not clear to what extent the self‐reactivity of IVIg preparations is due to the presence of natural IgG antibodies in the plasma pools used for fractionation, and to what extent it is due to the treatments that the IgG molecules have been subjected to during the fractionation process. We compared the binding of seven different commercial IVIg preparations to human liver antigens. All studied IVIg's could be clearly separated into two distinct groups: those that possess significant self‐reactivity and those with low binding to self‐antigens. Increased self‐binding was seen in the preparations produced using a fractionation step at low pH. The treatment of IVIg at low pH resulted in increasing the inhibitory effect of the pooled IgG on PHA‐induced proliferation of human peripheral blood mononuclear cells. IVIg's with high and low self‐binding may have different immunomodulating activities when infused to autoimmune patients.