The same HLA-DQ alleles determine either susceptibility or resistance to different coxsackievirus-mediated autoimmune...

An important characteristic of autoimmune diseases is their association with major histocompatibility complex class I and class II alleles. In this study, we compared insulin-dependent diabetes mellitus (IDDM) with idiopathic dilated cardiomyopathy (IDC) from a strictly immunologic perspective. Although the target organs are different, being in one case the insulin-producing beta cells of the pancreas and in the other case the myocytes of the heart, many aspects of the tissue-specific immune destruction are common. Similar yet different Coxsackievirus B strains with either pancreotropic or cardiotropic specificity are able to perpetrate the first injury of the respective target tissue. Their shared capacity of inducing a superantigenic reaction further enhances the damage. Once previously secluded autoantigens are then exposed to the immune system, the tissue injury is completed via a more conventional type of immune response. On the basis of the compounded results we obtained, it is possible to propose that the same HLA-DQ molecules which are able to protect the individuals from IDDM (e.g., HLA-DQA1*0102, DQB1*0602) seem to favour the enteroviral attack to the myocardium, while alleles which confer the strongest susceptibility to IDDM (e.g., DQA1*0301, DQB1*0302), seem unable to sustain the immune attack against the heart.