Antibodies against human heat-shock protein (hsp) 60 and mycobacterial hsp65 differ in their antigen specificity and complement-activating ability

Although complement activation appears to have an important role both in th e early and late phases of atherosclerosis, the exact mechanism of the init iation of this activation is still unknown. Since injuries of the endotheli al cells are known to result in increased stress-protein expression we test ed the complement-activating ability of recombinant human 60 kDa heat-shock protein (hsp60). Human hsp60 was found to activate the complement system i n normal human serum in a dose-dependent manner. Activation took place thro ugh the classical pathway. The lack of complement activation in agammaglobu linemic serum indicates that the classical pathway is triggered by anti-hsp 60 antibodies. Hsp60 activated complement in the sera of 74 patients with c oronary heart disease as well, and a strong positive correlation (r = 0.459 , P < 0.0001) was found between the extent of complement activation and the level of anti-hsp60 IgG antibodies but there was no correlation to the lev el of anti-hsp65 IgG antibodies. Further distinction between anti-hsp60 and anti-hsp65 antibodies was obtained from competitive ELISA experiments: bin ding of anti-hsp60 antibodies to hsp60-coated plates was inhibited only by recombinant hsp60 and vice versa, Our present findings indicate that anti-h sp60 and anti-hsp65 antibodies are distinct, showing only partial cross-rea ctivity, Since complement activation plays an important role in the develop ment of atherosclerosis and the levels of complement-activating anti-hsp60 antibodies are elevated in atherosclerosis-related diseases, our present fi ndings may have important pathological implications.