Association of serum antibodies to heat-shock protein 65 with coronary calcification levels - Suggestion of pathogen-triggered autoimmunity in early atherosclerosis

Background - Previous studies demonstrated an association between antibodies to mycobacterial heat-shock protein 65 (mHSP65) and carotid artery thickening. We examined whether mHSP65 antibodies are associated with levels of coronary calcification that appear to reflect preclinical coronary artery disease ( CAD). Methods and Results - Serum specimens from 201 healthy asymptomatic subjects (52% male; mean age, 56.6 years) undergoing electron-beam computed tomographic imaging were used to measure levels of mHSP65 and human HSP60 antibodies and antibodies to several infectious pathogens. We found that 84% of the study subjects had anti-mHSP65 IgG antibodies. Mean titers of mHSP65 antibodies were higher (1: 394 versus 1: 267, P = 0.012) in individuals with than in those without elevated levels of coronary calcium ( calcium score greater than or equal to 150). Increasing titers of mHSP65 antibodies were significantly associated, in a dose-response manner, with elevated levels of coronary calcification. Individuals with the highest titers of mHSP65 antibodies (greater than or equal to1: 800) had an adjusted odds ratio (OR) of 14.3 for having elevated coronary calcium (P = 0.004). Association of mHSP65 antibodies with elevated coronary calcification levels was independent of CAD risk factors after multivariate adjustment (P = 0.037). Interestingly, mHSP65 antibody titers were correlated with Helicobacter pylori infection (P = 0.004), which maintained significance after adjustment for CAD risk factors and seropositivities to other pathogens (adjusted OR, 3.1; 95% CI, 1.4 to 6.6). No association was found between antibodies to human HSP60 and levels of coronary calcification. Conclusions - Antibodies to mHSP65 are associated with elevated levels of coronary calcification and correlated with H pylori infection, suggesting that pathogen-triggered autoimmunity plays a role in early atherosclerosis.