IgG but not other classes of anti-[(H2A-H2B)-DNA] is an early sign of procainamide-induced lupus.
A longitudinal study was undertaken to characterize the autoantibodies induced during the course of procainamide treatment and to relate this information to the appearance of symptomatic drug-induced lupus. IgG, IgA, and IgM Abs to histones, native and denatured DNA, chromatin, and (H2A-H2B)-DNA were determined by ELISA in serial serum samples obtained over the course of an average of 2.1 yr on 22 patients undergoing treatment with procainamide and on an additional 9 patients after discontinuation of procainamide because of drug-induced lupus. Ten patients in the prospective group developed lupus-like symptoms after an average of 1.8 +/- 2.1 yr of procainamide treatment. Of the total of 19 patients with drug-induced lupus, 16 had IgG Abs to the (H2A-H2B)-DNA complex at the time of diagnosis; this autoantibody was first detected 0.9 +/- 1.3 yr before diagnosis in 7 patients. In contrast, the 9 patients who remained asymptomatic during treatment with procainamide for an average of 4.3 +/- 2.2 yr had negligible levels of IgG anti-[(H2A-H2B)-DNA], although IgA and IgM Abs of this specificity were not uncommon. Abs to denatured DNA and histones were elicited coordinately, but these specificities did not discriminate symptomatic from asymptomatic procainamide-treated patients. We conclude that chronic exposure to procainamide commonly elicited autoantibodies with specificities for denatured epitopes on DNA and histones and for native regions on the (H2A-H2B)-DNA subunit of chromatin. However, rapid switch to the IgG class of anti-[(H2A-H2B)-DNA] occurred only in patients who went on to develop symptomatic disease.
Rubin
R L
RL
W. M. Keck Autoimmune Disease Center, Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.
Burlingame
R W
RW
Arnott
J E
JE
Totoritis
M C
MC
McNally
E M
EM
Johnson
A D
AD
D000974:Antibodies, Antinuclear / Q000097:blood* / Q000145:classification; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D001402:B-Lymphocytes / Q000276:immunology; D004247:DNA / Q000276:immunology; D006657:Histones / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology*; D011342:Procainamide / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology
D000974:Antibodies, Antinuclear; D006657:Histones; D007074:Immunoglobulin G; D004247:DNA; D011342:Procainamide