Antiidiotypes against autoantibodies in pooled normal human polyspecific Ig.
We observed that pooled normal polyspecific human IgG for therapeutic use (IVIg) inhibited the binding of antithyroglobulin, anti-DNA and antiintrinsic factor antibodies to their autoantigens in vitro. The inhibitory effect of IVIg was dependent on interactions between the variable regions of IVIg and variable regions of the autoantibodies. Affinity chromatography of F(ab')2 fragments or of IgG containing anti-TG, anti-DNA, or anti-IF autoantibody activity on Sepharose-bound F(ab')2 from IVIg resulted in the specific retention of autoantibody activity, indicating that IVIg contain antiidiotypic antibodies against human autoantibodies. Inhibition of autoantibody activity by anti-Id in IVIg in vitro is dose dependent with maximal inhibition occurring at a specific molar ratio between patient's IgG and IVIg and shows a prozone phenomenon. The relative content in anti-Id against a particular autoantibody may differ between IVIg preparations. Affinity chromatography of IVIg on Sepharose-bound F(ab')2 fragments from IVIg also resulted in specific retention of anti-TG and anti-DNA activities that were found to be present in pooled normal immunoglobulins. The presence in IVIg of anti-Id against autoantibodies from patients and from normal individuals may provide a mechanism for the suppressive effect of IVIg in human autoimmune diseases and supports the concept of a functional idiotypic network regulating autoimmune responses in man.
Rossi
F
F
INSERM U 28, Hôpital Broussais, Paris, France.
Kazatchkine
M D
MD
D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000974:Antibodies, Antinuclear / Q000502:physiology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004247:DNA / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000502:physiology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007275:Injections, Intravenous; D007437:Intrinsic Factor / Q000276:immunology; D012685:Sepharose; D013954:Thyroglobulin / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D004247:DNA; D007437:Intrinsic Factor; D013954:Thyroglobulin; D012685:Sepharose