Antibodies to human heat-shock protein 60 are associated with the presenceand severity of coronary artery disease - Evidence for an autoimmune component of atherogenesis

Background-Antibodies to mycobacterial heat-shock protein (HSP) 65 have bee n reported to be associated with carotid artery thickening. We examined whe ther antibodies to human HSP60 are associated with the risk of coronary art ery disease (CAD). Methods and Results-Blood samples from 391 patients (62% men, mean age 57 y ears) being evaluated for CAD by coronary angiography were tested for IgG a ntibodies to human HSP60 by ELISA. We found that 75% of the study subjects had anti-HSP60 antibodies. The prevalence of CAD was increased in seroposit ive compared with seronegative patients (68% versus 49%, P=0.0009). Mean ti ters of HSP60 antibodies were higher in CAD patients than in non-CAD patien ts (P=0.008). No association between HSP60 antibodies and infection or infl ammation was found. Importantly, HSP60 antibodies were related to disease s everity. The prevalence of HSP60 antibodies was 76%, 80%, and 85% in patien ts with 1-, 2-, and 3-vessel disease, compared with 64% in patients without CAD (P for trend=0.003). A similar association between increasing antibody titers and number of diseased vessels was also found (P=0.03). Significant associations between antibodies to HSP60 and CAD severity persisted after adjustment for traditional risk factors by age, race, sex, smoking, diabete s, hypercholesterolemia, hypertension, and C-reactive protein levels. Adjus ted OR for number of vessels diseased was 1.86 (95% CI 1.13 to 3.04). Conclusions-This is the first study demonstrating a significant association between human HSP60 antibodies and both the presence and severity of CAD.