Heat shock protein as a predisposing and immunopotentiating factor in Kawasaki disease

Local inflammatory reactivation of a previous BCG inoculation site is a specific and early manifestations of Kawasaki disease (KD). It is postulated that the erythematous changes at the BCG site are part of a generalized activation of the immune system, and that molecules cross-reacting between the infectious agent involved and mycobacterial BCG antigens contribute to the inflammatory process. To detect the cross-reacting molecules, the antibody responses to mycobacterial antigens were examined in 21 patients by IgG-immuno-blotting using acute and convalescent phase sera. Markedly increased levels of antibody against mycobacterial 65kDa protein were detected in all convalescent but in none of the acute sera. Since the antibodies detected are also directed to recombinant 65kDa heat shock protein (HSP65), HSP65 may be related to the initial phase of KD. Moreover, peripheral lymphocytes from convalescent KD patients proliferated in culture in the presence of HSP65, suggesting the sensitization of lymphocytes to HSP65, and gamma delta TCR(+) T cells in the peripheral blood were increased in half the KD patients. Thus, HSP65 is a potent factor involved in activation of the immune system, and consequent endothelial damage in the initial phase of KD.