Serum Immunoglobulin G Antibodies to Chlamydial Heat Shock Protein 60 but Not to Human and Bacterial Homologs Are Associated With Coronary Artery Disease

Background—Evidence for an association between Chlamydia pneumoniae infection and coronary artery disease (CAD) has been reported by numerous studies, cross-reactive heat shock protein (Hsp) antibody responses have been causally linked to CAD, and the severity of chlamydial disease pathogenesis correlates with Hsp serology. Our aim was to determine if chlamydial Hsp (cHsp) antibody responses are predictive of CAD. Methods and Results—Patients were recruited in a case-control study: 250 cases had angiographically significant CAD (stenosis ≥70%), and 250 controls had normal coronary arteries (stenosis <10%). Serum immunoglobulin G reactivity to Hsp10 and Hsp60 antigens (chlamydial, Escherichia coli, and human), and C pneumoniae whole organisms were measured by ELISA. Univariate analysis confirmed that classical CAD risk factors were predictors of CAD. Univariate analysis showed that cHsp60 (P = 0.001, OR 3.9), cHsp10 (P =0.045, OR 3.8), E coli Hsp60 (P =0.04, OR 1.5) and C pneumoniae (P =0.03, OR 1.8) ELISA optical density (OD) values were significantly different between cases and controls. Multivariate analysis found that only upper-quintile cHsp60 seroreactivity remained a significant predictor of CAD after controlling for classical CAD risk factors and seroreactivity to the other antigens (cHsp60 OD, P =0.005, OR 3.9 per OD unit; cHsp60 quintile, 5 versus 1 to 4;P =0.01, OR 2.1). Conclusions—The presence of elevated anti-cHsp60 immunoglobulin G antibodies, but not anti-human or anti–E coli homologs, was independently associated with CAD. This finding argues against previous suggestions that cross-reactive or autoimmune Hsp60 responses may contribute to disease progression. High anti-cHsp60 antibody response appears to identify the subset of patients with chlamydial infection and significant CAD.