A monoclonal anti-idiotypic antibody against the antigen-combining site of anti-factor VIII autoantibodies defines and idiotope that is recognized by normal human polyspecific immunoglobulins for therapeutic use (IVIg).
The present study demonstrates that normal human immunoglobulins for therapeutic use (IVIg) contain anti-idiotypes that recognize an antigen-binding site-related idiotope of anti-Factor VIII autoantibodies defined by a mouse monoclonal antibody (MoAb). MoAb 20F2 was obtained by immunizing a mouse with affinity-purified anti-Factor VIII F(ab')2 fragments prepared from the IgG fraction of a patient with anti-Factor VIII autoantibodies. The monoclonal antibody was directed against an overlapping epitope on the antigen-binding site of the patient's anti-Factor VIII autoantibodies and the CH1 domain of human IgG1. The anti-Factor VIII activity of the patients's autoantibodies was neutralized by MoAb 20F2 in a dose-dependent manner. A fraction of the patient's anti-Factor VIII auto-antibodies was specifically retained on affinity columns of Sepharose-bound MoAb 20F2; anti-Factor VIII activity of antibodies in this fraction was totally inhibited by MoAb 20F2, indicating an idiotopic homogeneity of retained anti-Factor VIII autoantibodies. IVIg inhibited the anti-Factor VIII activity of 20F2 idiotope-positive F(ab')2 antibodies, thus indicating that the IVIg recognize the 20F2 idiotope on patient's autoantibodies. These observations further support the concept of the presence in IVIg of anti-idiotypes against autoantibodies associated with human autoimmune diseases.
Unité d'Immunopathologie Hôpital Broussais, Paris, France.
G
G
Dietrich
P
P
Pereira
M
M
Algiman
Y
Y
Sultan
M D
MD
Kazatchkine
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D002846:Chromatography, Affinity; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005169:Factor VIII / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007136:Immunoglobulins; D005169:Factor VIII