title: Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia.
abstract: Thrombocytopenia is a major adverse effect of several drug treatments. Rifampicin has been recognized as a cause of immune thrombocytopenia during intermittent high-dose therapy. We characterized the antibody of a patient who presented with purpura and thrombocytopenia during treatment of tuberculosis with rifampicin. Drug-dependent binding of the antibody to platelets was demonstrated by flow cytometry. In a glycoprotein-specific immunoassay, the binding epitope of the IgG antibody was found in the glycoprotein Ib/IX complex, using four different monoclonal antibodies (mAbs) against various epitopes on the GPIb/IX complex, as well as mAbs against GPIIb/IIIa, GPIa/IIa and GPIV. By immunoprecipitation of biotin-labelled platelets, reactivity of the antibody with GPIb/IX was found only in the presence of the drug. These findings clearly demonstrate that rifampicin induces the formation of drug-dependent antibodies capable of causing thrombocytopenia. The binding site of the rifampicin-dependent antibody, located in the GPIb/IX complex, seems to be a favoured target for antibodies induced by different drugs.
authors.affiliation: Department of Haematology-Oncology, School of Medicine, Catholic University of Chile, Santiago, Chile. jpereira@med.puc.fl
authors.forename: J
authors.initials: J
authors.lastname: Pereira
authors.forename: P
authors.initials: P
authors.lastname: Hidalgo
authors.forename: M
authors.initials: M
authors.lastname: Ocqueteau
authors.forename: M
authors.initials: M
authors.lastname: Blacutt
authors.forename: M
authors.initials: M
authors.lastname: Marchesse
authors.forename: Y
authors.initials: Y
authors.lastname: Nien
authors.forename: L
authors.initials: L
authors.lastname: Letelier
authors.forename: D
authors.initials: D
authors.lastname: Mezzano
mesh_terms: D000328:Adult; D000904:Antibiotics, Antitubercular / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D001792:Blood Platelets / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G; D008297:Male; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D011233:Precipitin Tests; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced* / Q000378:metabolism; D012293:Rifampin / Q000009:adverse effects*
chemical_list: D000904:Antibiotics, Antitubercular; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D019038:Platelet Glycoprotein GPIb-IX Complex; D012293:Rifampin