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Major Histocompatibility Complex Associations with Clozapine-Induced Agranulocytosis

The USA Experience

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Summary

In order to determine associations between the major histocompatibility complex (MHC) and the development of clozapine-induced agranulocytosis, HLA typing was performed in a group of 42 clozapine-treated patients, of whom 11 had developed this adverse reaction. Among the patients with agranulocytosis, 7 (63%) were of Ashkenazi Jewish background and 4 (37%) were non-Jewish. An association between the HLA-B38, -DR4, -DQw3 haplotype and clozapine-induced agranulocytosis was found in all Jewish cases (7/7; 100%); in contrast only 4 of 21 (19%) Jewish control (nonagranulocytic) patients carried this haplotype. Among non-Jewish patients the HLA-DR2, -DQw1 haplotype was present in 4 of 4 (100%) patients with clozapine-induced agranulocytosis and in only 3 of 10 (30%) ethnically matched control patients. Our results indicate that gene products within the MHC could be involved in clozapine-mediated haematological toxicity.

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Authors and Affiliations

  1. Division of Immunogenetics, Dana-Farber Cancer Institute, Center for Blood Research, and Harvard Medical School, Boston, Massachusetts, USA

    Juan J. Yunis & Edmond J. Yunis

  2. Long Island Jewish Medical Center and Albert Einstein College of Medicine, Hillside Hospital, Glen Oaks, New York, USA

    Jeffrey Lieberman

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  1. Juan J. Yunis
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  2. Jeffrey Lieberman
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  3. Edmond J. Yunis
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Clozaril®/Leponex®

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Yunis, J.J., Lieberman, J. & Yunis, E.J. Major Histocompatibility Complex Associations with Clozapine-Induced Agranulocytosis. Drug-Safety 7 (Suppl 1), 7–9 (1992). https://doi.org/10.2165/00002018-199200071-00005

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