Infusion of intravenous immunoglobulin (IVIg) has resulted in clinical improvement and/or a fall in autoantibody in a number of autoimmune and inflammatory diseases. Several lines of evidence demonstrate that IVIg may react with disease-associated autoantibodies through idiotypic interactions. In addition, infusion of IVIg results in changes in the expressed autoantibody repertoire that are dependent on interactions between variable regions of infused IgG and autoantibodies and in the subsequent alterations in the regulatory function of immune networks. Thus, pooled normal immunoglobulin restored in a patient with autoimmune thyroiditis the dynamics of spontaneous fluctuations of serum autoantibodies characteristic of physiological conditions. The ability of IVIg to interact with V regions of autoantibodies and with surface molecules of lymphocytes in vitro provides a basis for the selective modulation of B-cell clones observed in patients treated with immunoglobulins. The natural intrinsic complexity of IVIg provides a physiological rationale for immunoregulatory therapy of autoimmune disease.
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