Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mol Cell Probes. 2023 Jun;69:101914. doi: 10.1016/j.mcp.2023.101914. Epub 2023 Apr 21.
Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.
特发性膜性肾病（IMN）是一种单一器官自身免疫性疾病，其特征是针对足细胞蛋白的自身抗体，并被认为是成人肾病综合征最常见的病因。T 细胞在自身免疫中起着重要作用，因为它们促进 B 细胞的发育、抗体的产生、直接炎症和器官组织的细胞毒性。本研究调查了 T 淋巴细胞和其他免疫细胞上表达的抑制性免疫检查点（ICP）受体。因此，在治疗前从 IMN 患者中获得 PBMC，并使用实时 PCR 和 Western blot 试验分别在基因和蛋白质表达水平上检查 ICP 如程序性细胞死亡蛋白 1（PD-1）、细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）、淋巴细胞活化基因-3（LAG-3）和 T 细胞免疫球蛋白-3（TIM-3）的水平。结果表明，与对照相比，ICP 的基因表达水平显著降低，这通过蛋白表达的相关倍数变化依次得到验证。我们的研究表明，在治疗前，IMN 患者的 CTLA-4、PD-1、TIM-3 和 LAG-3 表达受损，这可能是治疗的潜在靶点。
