Genetic, Immunologic and Biotransformation Studies of Patients on Procainamide

TY - JOUR

T1 - Genetic, Immunologic and Biotransformation Studies of Patients on Procainamide

AU - Adams, Louis E.

AU - Balakrishnan, Kamala

AU - Belcher, Rick

AU - Mongey, Anne Barbara

AU - Hess, Evelyn V.

AU - Roberts, Stephen M.

AU - Thomas, T. J.

PY - 1993/4

Y1 - 1993/4

N2 - 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.

AB - 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.

KW - Autoimmunity

KW - Drug-related lupus

KW - Nitroprocainamide

KW - Procainamide

UR - http://www.scopus.com/inward/record.url?scp=0027315884&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027315884&partnerID=8YFLogxK

U2 - https://doi.org/10.1177/096120339300200205

DO - https://doi.org/10.1177/096120339300200205

M3 - Article

C2 - 8330041

SN - 0961-2033

VL - 2

SP - 89

EP - 98

JO - Lupus

JF - Lupus

IS - 2

ER -