title: Relative efficacy of intravenous immunoglobulin G in ameliorating thrombocytopenia induced by antiplatelet GPIIbIIIa versus GPIbalpha antibodies.
abstract: Intravenous immunoglobulin G (IVIG) is used to treat idiopathic thrombocytopenic purpura (ITP). Although many patients benefit from IVIG, some are refractory to this therapy. ITP is characterized by platelet clearance mediated primarily by antiplatelet antibodies against GPIIbIIIa and/or the GPIbalpha complex. These 2 groups of antibodies may induce ITP through different mechanisms. We tested the hypothesis that IVIG may not be equally effective in preventing ITP caused by anti-GPIIbIIIa versus anti-GPIbalpha antibodies in mice. Thrombocytopenia was induced in BALB/c mice using monoclonal antibodies against either mouse GPIIbIIIa (JON1, JON2, and JON3) or GPIbalpha (p0p3, p0p4, p0p5, p0p9, and p0p11). Pretreatment with IVIG significantly ameliorated ITP in all anti-GPIIbIIIa-injected animals. Conversely, IVIG failed to prevent ITP in all anti-GPIbalpha-treated mice, except for p0p4. These results were repeated in C57BL/6 mice, and with different IVIG preparations. These data in mice suggest that patients with ITP mediated by anti-GPIbalpha antibodies may be less responsive to IVIG treatment.
authors.affiliation: Canadian Blood Services, Ottawa, ON, Canada.
authors.forename: Michelle Lee
authors.initials: ML
authors.lastname: Webster
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Sayeh
authors.forename: Min
authors.initials: M
authors.lastname: Crow
authors.forename: Pingguo
authors.initials: P
authors.lastname: Chen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D001323:Autoantibodies / Q000097:blood*; D004353:Drug Evaluation, Preclinical; D016756:Immunoglobulins, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology*; D011292:Premedication; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex