The role of human leukocyte antigens in patients with heart failure

Öz

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.

Anahtar Kelimeler

• Human leukocyte antigen
• Heart failure
• Genetics

Kalp yetersizliği olan hastalarda insan lökosit antijenlerinin rolü

Öz

İlaç tedavilerindeki ve kardiyolojideki invaziv prosedürlerdeki ilerlemelere rağmen, kalp yetersizliği (KY) dünya çapında ölüm ve sakatlığın önde gelen nedenlerinden biri olmaya devam etmektedir. KY ilişkili yüksek ölüm ve hastalık oranları göz önüne alındığında, etiyolojisini -özellikle genetik temelini- anlamak çok önemlidir. Bu mekanizmaların aydınlatılması, tedavi seçeneklerini genişleterek hastaların yaşam beklentisini artırabilir, yaşam kalitesini iyileştirebilir ve sağlık hizmeti maliyetlerini düşürebilir. Bu incelemede, KY patofizyolojisi, tipleri, genetik temeli ve son olarak İnsan Lökosit Antijenlerinin (İLA) KY'deki rolü ele alındı. İLA sistemi, insan genomunun en polimorfik bölgelerinden biridir. Ana işlevi insan bağışıklık sistemini düzenlemektir. İLA moleküllerinin en önemli özelliği, çok çeşitli peptit sunumlarına izin vermeleri ve bağışıklık yanıtlarında bireyler arası değişkenliğe katkıda bulunmalarıdır. Bu polimorfizm, çok sayıda otoimmün ve inflamatuar hastalıkla ilişkilidir. Özellikle İLA-DQ2 ve İLA-DQ8 haplotipleri, anormal antijen sunumu nedeniyle çölyak hastalığı ve tip 1 diyabet mellitus için ge-netik risk faktörleri olarak kabul edilir. İnsan İLA-DQ alellerini ifade eden transgenik hayvan modelleri, otoimmün miyokardit ve ardından dilate kardiyomiyopati gelişimini göstermiştir. İLA haplotipleri şu anda KY için tek başına tanısal veya prognostik belirteçler olarak değerlendirilmemelidir. Bunun yerine, özellikle miyokardit ilişkili veya idiyopatik dilate kardiyomiyopati gibi seçilmiş fenotiplerde, daha geniş bir immünogenetik ve inflamatuar ağın bir bileşenini temsil edebilirler.

Anahtar Kelimeler

• İnsan lökosit antijeni
• Kalp yetersizliği
• Genetik

Kaynakça

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