Subject(s)
Antiphospholipid Syndrome/physiopathology , Autoimmune Diseases/physiopathology , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Autoimmune Diseases/immunology , Blood Platelets/metabolism , Eicosanoids/metabolism , Endothelium, Vascular/metabolism , Female , Fetal Diseases/etiology , Fetal Diseases/physiopathology , Fibrinolysis , Humans , Lupus Coagulation Inhibitor/physiology , Male , Pregnancy , Pregnancy Complications/immunology , Pregnancy Complications/physiopathology , Protein C/metabolism , Protein S/metabolism , Thromboplastin/metabolismABSTRACT
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.
Subject(s)
Antiphospholipid Syndrome/immunology , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Immunoglobulins, Intravenous/immunology , Lupus Coagulation Inhibitor/immunology , Abortion, Habitual/immunology , Adult , Aged , Cardiolipins/immunology , Female , Humans , Lupus Erythematosus, Systemic/immunology , Male , Mixed Connective Tissue Disease/immunology , Neutralization Tests , Partial Thromboplastin Time , Pregnancy , Thrombocytopenia/immunology , Thrombosis/immunologyABSTRACT
In a patient with a Lupus Anticoagulant (LA) and recurrent fetal loss, we observed a significant shortening of the APTT after high-dose intravenous immunoglobulin infusion (IVIg). The LA activity present in patient's serum and purified IgG was partially neutralized by IVIg in a dose-dependent way. In addition, IgG purified from IVIg and its F(ab')2 fragment neutralized LA activity of the patient's IgG. In both cases, the neutralization was dose-dependent and it was obtained with similar molar ratios. The "in vitro" neutralization of LA activity and the immediate shortening of the APTT after IVIg infusion, might be mediated through idiotype/antiidiotype interactions. On the other hand, the long-lasting effect of IVIg in this patient indicates that it may induce specific inhibition of autoantibody synthesis. We believe that IVIg should be considered as a therapeutic alternative for LA-related clinical disorders.
Subject(s)
Autoantibodies/immunology , Blood Coagulation Factors/immunology , Immunoglobulins/immunology , Abortion, Spontaneous/immunology , Adult , Blood Coagulation Tests , Dose-Response Relationship, Immunologic , Female , Fetal Death/immunology , Humans , Hydrolysis , Immunoglobulin G/isolation & purification , Immunoglobulins/administration & dosage , Infusions, Intravenous , Lupus Coagulation Inhibitor , Pepsin A , PregnancyABSTRACT
Erythrocytes from 42 systemic lupus erythematosus (SLE) patients and 80 healthy volunteers were tested for the immunoadherence (CR1) receptor reactivity, observed by hemagglutination (IAHA) when incubating erythrocytes and aggregated human gamma-globulin (AHGG)-complement in appropriate proportions. Reactivity was expressed as the highest two-fold dilution of AHGG (2n) that induced hemagglutination. Erythrocytes of 15 SLE patients (35.7%) showed reactivity compared with 70 normal controls (87.5%). Both groups showed a trimodal distribution of IAHA titers in accordance with the three phenotypic groups described by other authors. Of the healthy population 72.5% belong to the intermediate reactivity mode (2(6) to 2(8)) and 64.3% of the SLE patients to the low reactivity group (negative). There was no correlation between CR1 defective expression and conventional activity parameters. This erythrocyte receptor involved in the immunocomplex clearance process, which constitutes 95% of the circulating CR1, is another factor that contributes to the pathophysiology of the disease when it is defective.
Subject(s)
Erythrocytes/immunology , Lupus Erythematosus, Systemic/immunology , Receptors, Complement/analysis , Female , Hemagglutination Tests , Humans , Immune Adherence Reaction , Lupus Erythematosus, Systemic/blood , Male , Receptors, Complement/physiology , Receptors, Complement 3bABSTRACT
Erythrocytes from 42 systemic lupus erythematosus (SLE) patients and 80 healthy volunteers were tested for the immunoadherence (CR1) receptor reactivity, observed by hemagglutination (IAHA) when incubating erythrocytes and aggregated human gamma-globulin (AHGG)-complement in appropriate proportions. Reactivity was expressed as the highest two-fold dilution of AHGG (2n) that induced hemagglutination. Erythrocytes of 15 SLE patients (35.7
) showed reactivity compared with 70 normal controls (87.5
). Both groups showed a trimodal distribution of IAHA titers in accordance with the three phenotypic groups described by other authors. Of the healthy population 72.5
belong to the intermediate reactivity mode (2(6) to 2(8)) and 64.3
of the SLE patients to the low reactivity group (negative). There was no correlation between CR1 defective expression and conventional activity parameters. This erythrocyte receptor involved in the immunocomplex clearance process, which constitutes 95
of the circulating CR1, is another factor that contributes to the pathophysiology of the disease when it is defective.
