Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis.
BACKGROUND
Antibodies to mycobacterial heat-shock protein (HSP) 65 have been reported to be associated with carotid artery thickening. We examined whether antibodies to human HSP60 are associated with the risk of coronary artery disease (CAD).


RESULTS
Blood samples from 391 patients (62% men, mean age 57 years) being evaluated for CAD by coronary angiography were tested for IgG antibodies to human HSP60 by ELISA. We found that 75% of the study subjects had anti-HSP60 antibodies. The prevalence of CAD was increased in seropositive compared with seronegative patients (68% versus 49%, P:=0.0009). Mean titers of HSP60 antibodies were higher in CAD patients than in non-CAD patients (P:=0.008). No association between HSP60 antibodies and infection or inflammation was found. Importantly, HSP60 antibodies were related to disease severity. The prevalence of HSP60 antibodies was 76%, 80%, and 85% in patients 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, diabetes, hypercholesterolemia, hypertension, and C-reactive protein levels. Adjusted 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.
Cardiovascular Research Institute of the MedStar Research Institute, Washington Hospital Center, Washington, DC 20010, USA.
J
J
Zhu
A A
AA
Quyyumi
D
D
Rott
G
G
Csako
H
H
Wu
J
J
Halcox
S E
SE
Epstein
D001323:Autoantibodies / Q000032:analysis* / Q000502:physiology; D001424:Bacterial Infections / Q000276:immunology; D018834:Chaperonin 60 / Q000276:immunology*; D003327:Coronary Disease / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index; D013223:Statistics as Topic
D001323:Autoantibodies; D018834:Chaperonin 60