The role of human leukocyte antigens in patients with heart failure

Despite advances in drug therapies and invasive procedures in cardiology, heart failure (HF) remains one of the leading causes of mortality and morbidity worldwide. Given the high mortality and morbidity rates associated with HF, understanding its etiology—particularly its genetic basis—is crucial. Elucidating these mechanisms can expand therapeutic options, thereby improving patient life expectancy, enhancing quality of life, and reducing healthcare costs. This review discusses the human genome in the context of HF pathophysiology, its classifications, their genetic basis, and the specific role of Human Leukocyte Antigens (HLA) in HF. The HLA system is one of the most polymorphic regions of the human genome. Its main function is to regulate the human immune system. The most important characteristic of HLA mole-cules is that they allow for a wide variety of peptide presentations, contributing to inter-individual varia-bility in immune responses. This polymorphism is associated with numerous autoimmune and inflamma-tory diseases. In particular, HLA-DQ2 and HLA-DQ8 haplotypes are considered genetic risk factors for celiac disease and type 1 diabetes mellitus due to abnormal antigen presentation. Transgenic animal mod-els expressing human HLA-DQ alleles have demonstrated the development of autoimmune myocarditis progressing to dilated cardiomyopathy. HLA haplotypes should not currently be regarded as standalone diagnostic or prognostic markers for HF. Rather, they may represent one component of a broader immuno-genetic and inflammatory network, particularly in selected phenotypes such as myocarditis-related or idiopathic dilated cardiomyopathy.