Genetic, immunologic and biotransformation studies of patients on procainamide.
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.
Adams
L E
LE
Department of Medicine, Paul Hoxworth Blood Center, University of Cincinnati Medical Center, Ohio 45267-0563.
Balakrishnan
K
K
Roberts
S M
SM
Belcher
R
R
Mongey
A B
AB
Thomas
T J
TJ
Hess
E V
EV
D000368:Aged; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001711:Biotransformation; D015934:Complement C4a / Q000032:analysis / Q000235:genetics / Q000276:immunology; D015935:Complement C4b / Q000032:analysis / Q000235:genetics / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology; D006657:Histones / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D007375:Interleukin-1 / Q000378:metabolism; D008177:Lupus Vulgaris / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011342:Procainamide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000276:immunology* / Q000493:pharmacokinetics* / Q000652:urine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006680:HLA Antigens; D006683:HLA-DQ Antigens; C069546:HLA-DQ7 antigen; D006657:Histones; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C070890:4-nitroprocainamide; D015934:Complement C4a; D015935:Complement C4b; D011342:Procainamide