Association of serum antibodies to Heat-Shock protein 65 with coronary calcification levels. suggestion of Pathogen-Triggered autoimmunity in early atherosclerosis

Abstract

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, Pϭ0.012) in individuals with than in those without elevated levels of coronary calcium (calcium score Ն150). 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 (Ն1:800) had an adjusted odds ratio (OR) of 14.3 for having elevated coronary calcium (Pϭ0.004). Association of mHSP65 antibodies with elevated coronary calcification levels was independent of CAD risk factors after multivariate adjustment (Pϭ0.037). Interestingly, mHSP65 antibody titers were correlated with Helicobacter pylori infection (Pϭ0.004), 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.

Joint Effects of Antibody to Heat Shock Protein 60, Hypertension, and Diabetes on Risk of Coronary Heart Disease in Chinese

“…after angioplasty have been documented in several studies (5,15,(22)(23)(24), but the results are inconsistent (2,(4)(5)(6)(7). Our study is the largest case control study so far on the relationship between anti-Hsp60 and risk of CHD, providing evidence that increasing anti-Hsp60 concentrations are associated with CHD risk in a doseresponsive manner.…”

“…Coronary heart disease (CHD) 5 is a multifactorial disease, and autoimmunity is considered to be one of its most important mechanisms (1 ). Heat shock protein (Hsp) is a possible autoantigenic determinant that may play a significant role in the development of atherosclerosis.…”

C-Reactive Protein, Insulin Resistance, and Metabolic Syndrome in a Population With a High Burden of Subclinical Infection

“…IgG, IgA, and IgM antibodies to C. pneumoniae and IgG antibodies to other pathogens were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits (5). Obesity was defined as BMI Ն30 kg/m 2 , metabolic syndrome was defined by Adult Treatment Panel III criteria, and insulin resistance was defined by homeostasis model assessment (HOMA) (9).…”

Heat Shock Protein-60 and Risk for Cardiovascular Disease

“…The probable sources of these autoantibodies can be infections by distinct pathogens in various locations, such as lung (Chlamydia pneumonia [67,75] or Mycobacterium tuberculosis [75][76][77]), genital tract (Chlamydia trachomatis [78,79]), oral cavity (Porphyromonas gingivalis [70,80]), and stomach (Helicobacter pylori [81,82]). Also, antibodies that can destroy endothelial cells overexpressing HSP60 have been observed in viral (e.g.…”