Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network

Abstract

Infusion of intravenous immune globulin (IVIG) has resulted in clinical improvement and/or a fall in autoantibody titer in a number of autoimmune diseases in which direct or indirect evidence suggests a pathogenic role for autoantibodies. IVIG may react with disease-associated autoantibodies through idiotypic interactions as shown by the following lines of evidence: (1) inhibition of autoantibody activity in F(ab′) 2 fragments of patients' IgG by F(ab′) 2 fragments of IVIG; (2) retention of autoantibodies on affinity columns of Sepharose-bound F(ab′) 2 fragments of IVIG; and (3) recognition of the same idiotypic determinants on autoantibodies by heterologous anti-idiotypic antibodies and by IVIG. IVIG also interacts with idiotypic determinants on natural autoantibodies as indicated by the binding of monoclonal IgM secreted by Epstein-Barr virus-transformed normal human B cells to F(ab′) 2 fragments of IVIG and by idiotypic interactions between normal IgG antibodies within the IVIG preparations. Infusion of IVIG into patients with autoimmune diseases alters the kinetic behavior of disease-associated and natural autoantibodies of unrelated specificities. It is our view that IVIG is effective in autoimmune diseases not merely by a passive transfer of suppressive anti-idiotypes, but rather by imposing a normal function on the defective network in autoimmune patients. The intrinsic complexity of IVIG would provide a more logical (physiological) rationale for immunoregulatory therapy of autoimmune disease than idiotype-specific suppression.