Antiidiotypic suppression of autoantibodies with normal polyspecific immunoglobulins.
A mechanism by which therapeutic normal polyspecific immunoglobulins (IVIg) may suppress autoimmune responses in vivo is that of antiidiotypic suppression of autoantibodies mediated by anti-idiotypes present in IVIg. In vitro incubation with IVIg of either the plasma or the IgG fraction from plasma of patients with autoantibodies against procoagulant factor VIII (VIII:C), DNA, thyroglobulin, peripheral nerve and intrinsic factor resulted in dose-dependent inhibition of autoantibody activity. The pattern of inhibition curves showed a prozone phenomenon. Maximal inhibition was achieved at a ratio of patient's IgG to IVIg which was specific for each antibody tested. Inhibition was dependent on idiotypic/antiidiotypic interactions between autoantibodies and IVIg since: 1) F(ab')2 from IVIg inhibited autoantibody activity in F(ab')2 fragments from patients' IgG; 2) IVIg contained no antigen-like activity and no antibodies against the commonest allotypes expressed in F(ab')2 fragments of human IgG; 3) autoantibody activity in F(ab')2 fragments from patients' IgG was specifically retained on affinity columns of Sepharose-bound F(ab')2 fragments from IVIg. The presence of antiidiotypes against autoantibodies in pooled normal IgG supports the concept of a functional idiotypic network regulating autoimmune responses in man.
Rossi
F
F
INSERM U28, Hôpital Broussais, Paris.
Dietrich
G
G
Kazatchkine
M D
MD
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D005169:Factor VIII / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; D007136:Immunoglobulins; D007165:Immunosuppression Therapy; D066298:In Vitro Techniques
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; D007136:Immunoglobulins; D005169:Factor VIII