Neutralization of lupus anticoagulant activity by human immunoglobulin "in vitro".
We studied the in vitro effect of human intravenous immunoglobulin (IVIg) on the lupus anticoagulant (LA) activity present in sera of 11 patients. LA potency was determined in all the cases and a fixed dilution of each serum was chosen to perform the dose-dependent neutralization experiments. For each patient, the dilute serum was incubated for 3 h at 37 degrees C with phosphate buffer saline (PBS) alone or containing IVIg at final concentrations of 0 to 50 mg/ml. Aliquots of the incubation mixtures were added to equal volumes of normal plasma and APTTs were performed. IVIg partially neutralized the LA activity present in 10 out of 11 patients sera. These neutralizations showed an IVIg dose-dependent behaviour. Statistically significant neutralizations were observed at least at one molar ratio (MR = [IVIg]/patient's [IgG] or [IgM]). In every case, a particular MR was found in which the neutralization was maximal (N%max). The N%max ranged from 33.6% to 79.5%. Eight patients showed maximal LA neutralization at MR ranging from 8.9 to 56.8. In one patient with drug-induced LA and another exhibiting LA cofactor effect, MRs were more elevated. We found poor negative correlation between N%max and LA potency (r = -0.46) or N%max and MR of N%max (r = 0.47), although no statistic significance was reached. However, there was good agreement between LA potency and MR of N%max (r = 0.98, p less than 0.001). We have shown that IVIg may neutralize LA activity in vitro. In view of these results, we believe that IVIg should be considered as an alternative therapy in patients with LA-related clinical complications.
Said
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Haemostasis and Thrombosis Section, Faculty of Pharmacy and Biochemistry, Hospital de Clínicas, University of Buenos Aires, Argentina.
Martinuzzo
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Carreras
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D000026:Abortion, Habitual / Q000276:immunology; D000328:Adult; D000368:Aged; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D016682:Lupus Coagulation Inhibitor / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008947:Mixed Connective Tissue Disease / Q000276:immunology; D009500:Neutralization Tests; D010314:Partial Thromboplastin Time; D011247:Pregnancy; D013921:Thrombocytopenia / Q000276:immunology; D013927:Thrombosis / Q000276:immunology
D002308:Cardiolipins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D016682:Lupus Coagulation Inhibitor