Bajcsi Dóra, Maróti Zoltán, Endreffy Emőke, Légrády Péter, Ábrahám György, Iványi Béla
Department of Internal Medicine, Albert Szent-Györgyi Medical Centre, Albert Szent-Györgyi Medical School, University of Szeged, 6725 Szeged, Hungary.
Department of Pediatrics, Albert Szent-Györgyi Medical Centre, Albert Szent-Györgyi Medical School, University of Szeged, 6720 Szeged, Hungary.
Int J Mol Sci. 2025 Sep 4;26(17):8621. doi: 10.3390/ijms26178621.
With primary membranous nephropathy (pMN), the genetic background is not precisely known. Certain HLA-DQ serotypes however like HLA-DQ 2.5, and single-nucleotide polymorphisms (SNPs) in the phospholipase A2 receptor 1 (PLA2R1) gene pose a risk for the development of pMN. As antigen presentation is linked to a 3-dimensional conformation of the HLA-DQA/DQB dimer, we thought that the specific HLA-DQ haplotype combinations might also be risk factors in the evolution of MN. The HLA-DQ haplotype combinations and the PLA2R1 gene risk variant (rs4664308) genotypes were examined in 67 patients with MN (52 primary, 15 secondary [sMN]) and 77 controls. Based on the presence or absence of PLA2R1 risk alleles, we used a scoring system to assess the risk and to identify protective HLA-DQ haplotype combinations. The HLA-DQ 2.5 serotype was significantly enriched in both pMN and sMN patients compared to the controls. The pMN group had a significantly higher frequency of the PLA2R1 risk allele compared to the sMN group and the controls. HLA-DQ 2.5 appeared to carry the highest risk for the development of pMN, while HLA-DQ 7.5 and 6.2 seemed to be protective. Our results indicate that the HLA-DQ 2.5 probably carries the highest risk in both pMN and sMN, suggesting that this serotype has less specificity for antigens, and it induces an autoimmune response. Here, PLA2R1 played a role in the development of pMN but not in sMN.
对于原发性膜性肾病（pMN），其遗传背景尚不完全清楚。然而，某些HLA - DQ血清型，如HLA - DQ 2.5，以及磷脂酶A2受体1（PLA2R1）基因中的单核苷酸多态性（SNP）会增加pMN发病的风险。由于抗原呈递与HLA - DQA/DQB二聚体的三维构象相关，我们认为特定的HLA - DQ单倍型组合可能也是MN发病过程中的危险因素。我们检测了67例MN患者（52例原发性，15例继发性[sMN]）和77例对照的HLA - DQ单倍型组合以及PLA2R1基因风险变异体（rs4664308）的基因型。基于PLA2R1风险等位基因的有无，我们使用评分系统来评估风险并识别具有保护作用的HLA - DQ单倍型组合。与对照组相比，pMN和sMN患者中HLA - DQ 2.5血清型均显著富集。与sMN组和对照组相比，pMN组中PLA2R1风险等位基因的频率显著更高。HLA - DQ 2.5似乎是pMN发病的最高风险因素，而HLA - DQ 7.5和6.2似乎具有保护作用。我们的结果表明，HLA - DQ 2.5可能在pMN和sMN中都具有最高风险，这表明该血清型对抗原的特异性较低，并能诱导自身免疫反应。在这里，PLA2R1在pMN的发病过程中起作用，但在sMN中不起作用。
