Hakimi Pooria, Zaboli Kasra Arbabi, Golbabapour-Samakoush Mohammadreza, Azizimohammadi Susan, Soleimani Fatemeh, Salmani Mohammad Hosein, Teimoori-Toolabi Ladan
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Hajar Hospital, Tehran, Iran.
J Cell Mol Med. 2025 May;29(9):e70570. doi: 10.1111/jcmm.70570.
The HLA system is a crucial immune response component against infectious agents, including SARS-CoV-2. Certain polymorphisms may impart varying levels of protection or vulnerability to COVID-19. This research aims to understand the possible relationship between HLA polymorphisms and the susceptibility to COVID-19 and its severity. We recruited 290 hospitalised Iranian COVID-19 patients (130 severe and 160 moderate). Using PCR-SSP methods, we conducted a detailed analysis of polymorphisms in HLA class I (HLA-A, HLA-B, and HLA-C) and II (HLA-DRB1 and HLA-DQB1) molecules at low resolution. The study found that certain HLA alleles, including HLA-B49, HLA-B52, HLA-C12, HLA-DRB104, and HLA-DQB105, were associated with disease susceptibility. Additionally, HLA-A23, DRB110, and DRB113 were indicators of disease severity. The study also noted that individuals carrying the HLA-A23 allele showed a significant decrease in lymphocyte levels and an elevated likelihood of developing thrombosis. We hypothesise that a maladaptive immune response may occur based on these findings. This might be due to the strong affinity of the HLA-A23 allele group for presenting a wide range of SARS-CoV-2 peptides. Such a presentation possibly leads to a cytokine storm, followed by lymphocyte apoptosis and an increase in platelet count.
HLA系统是针对包括SARS-CoV-2在内的感染因子的关键免疫反应组成部分。某些多态性可能赋予对COVID-19不同程度的保护或易感性。本研究旨在了解HLA多态性与COVID-19易感性及其严重程度之间的可能关系。我们招募了290名住院的伊朗COVID-19患者（130名重症患者和160名中度患者）。使用PCR-SSP方法，我们对低分辨率下HLA I类（HLA-A、HLA-B和HLA-C）和II类（HLA-DRB1和HLA-DQB1）分子的多态性进行了详细分析。研究发现，某些HLA等位基因，包括HLA-B49、HLA-B52、HLA-C12、HLA-DRB104和HLA-DQB105，与疾病易感性相关。此外，HLA-A23、DRB110和DRB113是疾病严重程度的指标。该研究还指出，携带HLA-A23等位基因的个体淋巴细胞水平显著降低，发生血栓形成的可能性增加。基于这些发现，我们假设可能会发生适应性不良的免疫反应。这可能是由于HLA-A23等位基因组对呈现多种SARS-CoV-2肽具有很强的亲和力。这种呈现可能导致细胞因子风暴，随后淋巴细胞凋亡和血小板计数增加。
