Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia.
We previously described an ELISA to measure the inhibition of platelet glycoprotein IIb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes and/or anti-platelet antibodies from patients with immune thrombocytopenia (ITP) or HIV-related ITP. Circulating immune complexes (CIC) were the main factor in the inhibition of GPIIb/IIIa binding to fibrinogen in HIV-related ITP, whereas in non-HIV ITP, inhibition was only partially due to CIC; anti-platelet antibodies specific to GPIIIa were also shown to play a role. In this study, we correlated the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera of patients with ITP and HIV-related ITP. In the majority of the patients' sera tested, as the platelet count increased following the administration of IVIG, the degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also observed a decrease and/or disappearance of the antibodies specific to GPIIb and/or GPIIIa after IVIG administration. In HIV-seronegative ITP patients, the decrease or disappearance of anti-platelet antibodies directly correlated with the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG supernatants of sera which contained anti-platelet antibodies. These findings suggest that IVIG directly affects the binding of CIC and anti-platelet antibodies to platelets and thereby improves platelet survival. Our results also suggest that the anti-idiotypic effect may contribute to IVIG's therapeutic action. In contrast, in the HIV-seropositive group, the decreased inhibition by PEG precipitates after IVIG administration was more strongly associated with an increase in the platelet count.
Kamiyama
M
M
Saint Michael's Medical Center, Newark, New Jersey.
Yoshimura
Y
Y
Chen
K
K
Arkel
Y S
YS
D000906:Antibodies / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D000936:Antigen-Antibody Complex / Q000378:metabolism / Q000502:physiology; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D005591:Chemical Fractionation; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007154:Immune System Diseases / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects*; D013921:Thrombocytopenia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*
D000906:Antibodies; D000936:Antigen-Antibody Complex; D016756:Immunoglobulins, Intravenous; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen