Antibodies against heat shock protein 60 derived from Helicobacter pylori: Diagnostic implications in cardiovascular disease

Immune responses against heat shock protein 60 (HSP60) of pathogen-origin are thought to be defensive events which, due to molecular mimicry, misdirect to a human counterpart. Therefore, atherosclerosis may be serologically predicted by anti-HSP60 antibodies (Abs). In the present study, we analyzed the clinical prevalence of the serum IgG Abs against Helicobacter pylori (Hp)-derived HSP60 (Hp-HSP60) or its peptide fragments in patients with cardiovascular disease (CVD; n = 250), as compared to those in age- and gender-matched non-CVD patients (n = 293). Anti-Hp cell lysate Abs frequently appeared in Hp-infected patients who were not associated with CVD. In contrast, Abs against the particular amino acid sequence Hp-HSP60II3 (II3 region, Glu141–Leu160, in Hp-HSP60) predominantly appeared in CVD patients, as well as IgG anti-human HSP60 (Hu-HSP60w). Furthermore, neither titer of anti-Hp-HSP60II3 nor anti-Hu-HSP60w Abs was correlated with the levels of high sensitivity C-reactive protein (hsCRP). This data strongly suggested that IgG anti-Hp-HSP60II3 Abs cross-reacted with Hu-HSP60w were independent diagnostic markers relevant to CVD. Further, the 20 amino acid residues (Glu141–Leu160) might be predominant CVD-associated epitopes that induce anti-Hu-HSP60 auto-Abs, whose location was predicted in the tertiary structure of Hu-HSP60.