Complement activating antibodies against the human 60 kDa heat shock protein as a new independent family risk factor of coronary heart disease

Abstract

Background: Several groups have reported high levels of antibodies against 60 kDa heat shock proteins (hsp) associated with coronary heart disease. Methods and results: Complement activating (CA) antihsp60 autoantibodies were measured by the AtheroRisk kit (CardioPath Ltd, Alloa, UK), in parallel with IgG antibodies to human hsp60 and mycobacterial hsp65 by ELISA in 32 healthy children (18 boys, 14 girls, 11.8±4.0 years). At least one of the parents of these children had a history of myocardial infarction before 55 years of age (high family risk (HFR) group). The control group consisted of 63 healthy children (31 boys, 32 girls, 9.0±3.6 years) without known family history of coronary heart disease (CHD), hypertension, and diabetes mellitus. Concentrations of CA antihsp60 antibodies were significantly (P = 0.021) higher in the HFR group than in the control group. Also in the HFR group, significantly (P = 0.004) lower high-density lipoprotein cholesterol (HDL-C)-cholesterol (measured enzymatically) and significantly (P = 0.020) higher low-density lipoprotein cholesterol (LDL-C)-cholesterol levels (calculated by the Friedewald formula) were observed when compared with the controls. The difference in the CA antihsp60 antibody levels between the HFR and control groups remained significant even after adjustments for age, smoking, HDL-cholesterol, LDL-cholesterol levels, and white blood cell count. Children with high (in the highest quartile) CA antihsp60 antibody levels compared with those with normal levels of these antibodies also had adjusted odds ratios (OR) of 9.80 (2.15-44.58,P = 0.003), indicating high family risk. No significant difference in the IgG antihsp antibody levels was observed. Conclusions: These findings indicate that high levels of CA autoantibodies against hsp60 can be considered to be a novel family risk factor of CHD, independent of HDL- and LDL-cholesterol levels.