GENETIC, IMMUNOLOGICAL AND BIOTRANSFORMATION STUDIES OF PATIENTS ON PROCAINAMIDE

被引:24
作者
ADAMS, LE
BALAKRISHNAN, K
ROBERTS, SM
BELCHER, R
MONGEY, AB
THOMAS, TJ
HESS, EV
机构
[1] UNIV CINCINNATI, MED CTR,DEPT MED,DIV IMMUNOL,ML 563, 231 BETHESDA AVE, CINCINNATI, OH 45267 USA
[2] UNIV CINCINNATI, MED CTR, PAUL HOXWORTH BLOOD CTR, HISTOCOMPATIBIL LAB, CINCINNATI, OH 45267 USA
[3] UNIV FLORIDA, CTR ENVIRONM & HUMAN TOXICOL, GAINESVILLE, FL 32611 USA
[4] UMDNJ, ROBERT WOOD JOHNSON MED SCH,CLIN RES CTR,DEPT MED, DIV RHEUMATOL,PROGRAM CLIN PHARM, NEW BRUNSWICK, NJ USA
关键词
AUTOIMMUNITY; PROCAINAMIDE; NITROPROCAINAMIDE; DRUG-RELATED LUPUS;
D O I
10.1177/096120339300200205
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:89 / 98
页数:10
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