In vivo efficacy of intravenous gammaglobulins in patients with lupus anticoagulant is not mediated by an anti-idiotypic mechanism.
The authors have investigated the presence in commercially available intravenous gammaglobulins (IVIg) of anti-idiotypic antibodies directed to Lupus Anticoagulant (LA). In vitro incubation of 4 LA plasmas with increasing concentrations of IVIg (from 0 to 39 mg/ml) resulted in a dose-dependent inhibition of LA activity (the highest inhibitions ranged from 14.0 to 53.4%). Similar results were obtained when patients' plasma was substituted with total IgG (the highest inhibitions ranged from 43.0 to 55.0% and were obtained at IgG:IVIg molar ratios ranging from 1:15 to 1:50). Also the incubation of patients' F(ab')2 with F(ab')2 from IVIg produced a similar dose-dependent inhibition of LA activity. These data are suggestive of an in vitro idiotypic-anti-idiotypic interaction between LA and IVIg. However, when injected in patients with LA, IVIg do not seem to operate by this mechanism of action. In fact, reduction or disappearance of LA was only observed in 2 out of 4 patients; also the quick reappearance of LA activity was not consistent with the time course of anti-idiotypic response. Finally, this effect was reached by half the IVIg concentrations necessary to produce an appreciable inhibitory effect on LA activity in vitro. Thus, it is concluded that, even if IVIg contain anti-idiotypic antibodies reacting with LA, the clinical efficacy of IVIg treatment in patients with these autoantibodies should be attributed to other mechanisms.
Galli
M
M
Department of Hematology, Ospedali Riuniti, Bergamo, Italy.
Cortelazzo
S
S
Barbui
T
T
D000328:Adult; D000743:Anemia, Hemolytic / Q000628:therapy*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001327:Autoimmune Diseases / Q000628:therapy; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007275:Injections, Intravenous; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D013921:Thrombocytopenia / Q000628:therapy; D005719:gamma-Globulins / Q000627:therapeutic use*
D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; D016682:Lupus Coagulation Inhibitor; D005719:gamma-Globulins