IGG BUT NOT OTHER CLASSES OF ANTI-[(H2A-H2B)-DNA] IS AN EARLY SIGN OFPROCAINAMIDE-INDUCED LUPUS

A longitudinal study was undertaken to characterize the autoantibodies induced during the course of procainamide treatment and to relate thi s information to the appearance of symptomatic drug-induced lupus. IgG , IgA, and IgM Abs to histones, native and denatured DNA, chromatin, a nd (H2A-H2B)-DNA were determined by ELISA in serial serum samples obta ined over the course of an average of 2.1 yr on 22 patients undergoing treatment with procainamide and on an additional 9 patients after dis continuation of procainamide because of drug-induced lupus. Ten patien ts in the prospective group developed lupus-like symptoms after an ave rage of 1.8 +/- 2.1 yr of procainamide treatment. Of the total of 19 p atients with drug-induced lupus, 16 had IgG Abs to the (H2A-H2B)DNA co mplex at the time of diagnosis; this autoantibody was first detected 0 .9 +/- 1.3 yr before diagnosis in 7 patients. In contrast, the 9 patie nts who remained asymptomatic during treatment with procainamide for a n average of 4.3 +/- 2.2 yr had negligible levels of IgG anti-[(H2A-H2 B)-DNA], although IgA and IgM Abs of this specificity were not uncommo n. Abs to denatured DNA and histones were elicited coordinately, but t hese specificities did not discriminate symptomatic from asymptomatic procainamide-treated patients. We conclude that chronic exposure to pr ocainamide commonly elicited autoantibodies with specificities for den atured epitopes on DNA and histones and for native regions on the (H2A -H2B)-DNA subunit of chromatin. However, rapid switch to the IgC class of anti-[(H2A-H2B)-DNA] occurred only in patients who went on to deve lop symptomatic disease.