[HLA polymorphism in the susceptibility or resistance to dilated cardiomyopathy]

Abstract

Much of the surrounding studies on the association between HLA and diseases reflects a new insight into the key role of HLA molecules in the generation and regulation of the immune response. HLA molecules, on the surface of antigen presenting cells, bind foreign peptides. This HLA-antigen complex is then recognized by T lymphocytes and triggers the alloresponse against the peptide. Since many diseases associated with peculiar HLA antigens are thought to be autoimmune, the idea that certain Major Histocompatibility Complex (MHC) molecules could form complexes with self-peptides in anomalous ways, leading to an autoimmune reaction, is particularly attractive. Recent advances in molecular technology, x-ray crystallography and DNA studies have allowed the determination of the three-dimensional structure of some HLA class I and II molecules and also the amino acid sequences involved in binding of antigen fragments. This new information has prompted a search for differences, at the amino acid level, between HLA alleles previously shown to be positively or negatively associated with a pathology. Our own experience on the immunogenetic aspect of dilated cardiomyopathy (DCM) allowed us to assess some predisposing (HLA-DR4, DR5, C4A4) and protective (HLA-DR3) factors for DCM. Clinical heterogeneity also seems to imply a peculiar genetic background. The actual research is addressed to the study of the antigen binding site sequences and to the consideration of other new loci such as those entrapped within the HLA class III subregion (HSP70) and those lying within the class II region (PSF).