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.