Figure 1

Research strategies for identifying risk HLA of cardiac phenotypes in patients with CS. (a) Following conventional HLA analyses, prevalence of HLA alleles or haplotypes were compared between case and control groups. Associations between the risk alleles or haplotypes detected and cardiac phenotypes. (b) From an autoimmune perspective, the hetero-dimeric structure of HLA-II molecules (of the 68 patients with CS) and their binding affinity (BA) to possible antigenic epitopes (of 172 proteins) were taken into consideration. After the comprehensive calculation of BA, the combinations of HLA-II haplotypes and epitopes with high BA were extracted. Associations between HLA-II haplotypes with high BA and cardiac phenotypes. (c) Five anchor pockets in the epitope-binding domains of HLA-II molecules determine their BA to various epitopes. HLA-II haplotypes with similar BA patterns were grouped into an HLA heterodimeric haplotypes. This process was validated by homology of their amino acid residues in the peptide binding domains. (d) The possibility of auto-immunogenicity by the risk HLA haplotypes (or heterodimeric haplotypes) was considered with the mechanism of molecular mimicry. We used BLAST-P to look for epitopes from proteins expressed in infectious bacteria, which were homologous to the human epitopes with high BA.