An antibody from a patient with ranitidine-induced thrombocytopenia recognizes a site on glycoprotein IX that is a favored target for drug-induced antibodies. Blood 1998 Oct 01;92(7):2359-65
Date
09/25/1998Pubmed ID
9746775Scopus ID
2-s2.0-0032190417 (requires institutional sign-in at Scopus site) 51 CitationsAbstract
Although thrombocytopenia associated with the use of histamine H2 receptor (H2R) antagonists has been described, a drug-dependent, platelet-reactive antibody has not previously been identified in such cases. We studied serum from a patient who developed acute, severe thrombocytopenia after exposure to the H2 receptor antagonist, ranitidine, and identified an antibody that reacted with normal platelets in the presence of this drug at pharmacologic concentrations. In flow cytometric and immunoprecipitation studies, the antibody was shown to be specific for the glycoprotein Ib/IX complex (GPIb/IX). From the pattern of monoclonal antibody (MoAb) inhibition and the reactions of antibody with Chinese hamster ovary (CHO) cells transfected with GPIX and GPIbbeta, we found that the patient's antibody is specific for an epitope on GPIX close to, or identical with a site recognized by the MoAb SZ1 that is a common target for antibodies induced by quinine and quinidine, drugs structurally unrelated to ranitidine. These findings provide evidence that immune thrombocytopenia can be caused by sensitivity to an H2 R antagonist and suggest that the SZ1 binding site on GPIX may be a common target for drug-induced antibodies. Further studies of the epitope for which SZ1 is specific may provide clues to the mechanism(s) by which drugs promote tight binding of antibody to a membrane glycoprotein and cause platelet destruction in patients with drug sensitivity.
Author List
Gentilini G, Curtis BR, Aster RHAuthor
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAnimals
Anti-Ulcer Agents
Antibodies, Monoclonal
Antibody Specificity
Antigen-Antibody Reactions
Autoantibodies
Autoimmune Diseases
Blood Platelets
CHO Cells
Cimetidine
Cricetinae
Cricetulus
Epitopes
Famotidine
Female
Flow Cytometry
Histamine H2 Antagonists
Humans
Molecular Structure
Nizatidine
Platelet Glycoprotein GPIb-IX Complex
Precipitin Tests
Protein Conformation
Quinidine
Quinine
Ranitidine
Recombinant Fusion Proteins
Structure-Activity Relationship
Thrombocytopenia
Transfection