Modulation of autoimmunity by intravenous immune globulin through interaction with the function of the immune/idiotypic network.
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.
Dietrich
G
G
Institut National de la Sante et de la Recherche Medicale (INSERM), Paris, France.
Kaveri
S V
SV
Kazatchkine
M D
MD
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001327:Autoimmune Diseases / Q000628:therapy; D015551:Autoimmunity; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000627:therapeutic use
D000888:Antibodies, Anti-Idiotypic; D016756:Immunoglobulins, Intravenous