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Genetic, Immunologic and Biotransformation Studies of Patients on Procainamide

Division of Immunology, Department of Medicine and the Histocompatibility Laboratory, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Cincinnati, Ohio

Kamala Balakrishnan

Division of Immunology, Department of Medicine and the Histocompatibility Laboratory, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Cincinnati, Ohio

Stephen M. Roberts

Center for Environmental and Human Toxicology, University of Florida, Gainsville, Florida

Rick Belcher

Division of Immunology, Department of Medicine and the Histocompatibility Laboratory, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Cincinnati, Ohio

Anne-Barbara Mongey

Division of Immunology, Department of Medicine and the Histocompatibility Laboratory, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Cincinnati, Ohio

T.J. Thomas

Department of Medicine, Division of Rheumatology, Program in Clinical Pharmacy, Clinical Research Center, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA

Evelyn V. Hess

Division of Immunology, Department of Medicine and the Histocompatibility Laboratory, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Cincinnati, Ohio

This report represents follow-up observations of a unique long-term study of patients on procainamide (PA) for various cardiac arrhythmias. Serologic and clinical evaluations associated with drug-related autoimmunity were assessed and patients were characterized for factors postulated to influence susceptibility to autoimmunity, including acetylator phenotype, oxidative metabolism of PA, HLA class profile, and production of interleukin-1 (IL-1) and tumor necrosis factor (TNF). Fifty-two percent had IgM and 70% IgG antibodies to total histones; 67% had IgG antibodies to histone H2A/H2B. Patients were equally divided between fast and slow acetylators. N-oxidative metabolism of PA was indicated by the presence of urinary nitroprocainamide, which correlated with elevated titers of antihistone antibodies. There was a significant incidence of the DQw7 split of DQw3 in PA patients when compared to controls, and the frequency of antibodies to total histones and H2A/H2B was significantly increased in the DQw7 patients. C4A*QO and C4B*QO alleles were more frequent in the PA patients than in controls. IL-1 and TNF production was not different in patients compared to controls. These data suggest that certain genetic factors may serve as markers for PA-related autoimmunity.

Key Words: Autoimmunity • Procainamide • Nitroprocainamide • Drug-related lupus

Lupus, Vol. 2, No. 2, 89-98 (1993)
DOI: 10.1177/096120339300200205


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