Human Leukocyte Antigen Determinants in Myocarditis and Dilated Cardiomyopathy

PURPOSE OF REVIEW: Myocarditis, defined as inflammation of heart muscle, can be triggered by viral infection or have an autoimmune origin. In some cases, it progresses to dilated cardiomyopathy (DCM) and heart failure. The human leukocyte antigen (HLA) system is important in adaptive immunity by influencing antigen presentation and autoimmunity. This review intends to clarify the role of HLA polymorphisms in the progression, resistance, and outcomes of myocarditis and DCM. RECENT FINDINGS: Evidence indicates that HLA is linked to myocarditis and DCM through familial aggregation, myocardial HLA upregulation, circulating cardiac autoantibodies, candidate association studies, genome-wide association signals at chromosome 6p21, and transgenic models demonstrating HLA-restricted disease susceptibility. HLA alleles influence viral clearance, molecular mimicry, autoimmune priming, cytokine signaling, and pathogen-specific autoantibody production. Translation of this evidence into clinical practice has been limited by modest effect sizes, population variability, and the lack of genotype-guided therapies. Using HLA as a risk-stratification tool can allow more accurate surveillance and immunomodulatory strategies for myocarditis and DCM. Future research priorities should include multi-ethnic HLA studies, viral epitope mapping, integration of immune profiling, and HLA-stratified clinical trials.