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(Circulation. 2004;109:36-41.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Association of Serum Antibodies to Heat-Shock Protein 65 With Coronary Calcification Levels

Suggestion of Pathogen-Triggered Autoimmunity in Early Atherosclerosis

Jianhui Zhu, MD, PhD; Richard J. Katz, MD; Arshed A. Quyyumi, MD; Daniel A. Canos, MS; David Rott, MD; Gyorgy Csako, MD; Alexandra Zalles-Ganley, BS; Jibike Ogunmakinwa, BS; Alan G. Wasserman, MD; Stephen E. Epstein, MD

From the Cardiovascular Research Institute, Washington Hospital Center (J.Z., D.A.C., D.R., A.Z.-G., J.O., S.E.E.), and George Washington University (R.J.K., A.G.W.), Washington, DC; Emory University Hospital, Atlanta, Ga (A.A.Q.); and the Clinical Center, National Institutes of Health, Bethesda, Md (G.C.).

Correspondence to Dr Jianhui Zhu, Cardiovascular Research Institute, Washington Hospital Center, 108 Irving St, NW, GHRB Room 217, Washington, DC 20010. E-mail jianhui.zhu{at}medstar.net

Received April 14, 2003; de novo received August 1, 2003; revision received September 22, 2003; accepted September 22, 2003.

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 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 (1:800) 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.

Key Words: proteins • infection • calcification

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