title: Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to platelets by sera from patients with immune thrombocytopenia.
abstract: 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.
authors.affiliation: Saint Michael's Medical Center, Newark, New Jersey.
authors.forename: M
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: Y S
authors.initials: YS
authors.lastname: Arkel
mesh_terms: 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*
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D016756:Immunoglobulins, Intravenous; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen