Laboratory Medicine Center, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Nucleosides Nucleotides Nucleic Acids. 2024;43(3):230-248. doi: 10.1080/15257770.2023.2253276. Epub 2023 Sep 9.
Multiple myeloma (MM) is a malignant disorder characterised by progressive immune dysregulation. The importance of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) in MM has been documented in various populations, but studies have been limited to the Chinese cohort. In the present study, we examined the role of PD-1/PDL-1 in large cohorts of Chinese patients with MM and healthy controls to reveal a possible association with MM. Three hundred thirty-four MM patients and 202 healthy age-sex-matched subjects were enrolled in the present study. Serum levels of PD-1 and PD-L1 were quantified by ELISA. Percentages of T cells (CD4 and CD8 T cells) expressing PD-1 receptor were assessed by flow cytometry. Variants in PD-L1 (rs4143815) and PD-1 gene (rs2227981, rs2227982, rs7421861 and rs11568821) were genotyped by PCR-RFLP method. Patients with multiple myeloma had higher levels of PD-1 and PDL-1 than healthy controls, indicating an important role for programmed cell death protein-1 and its ligand in the pathogenesis of MM. T cells expressing PD-1 receptors were also significantly higher in MM patients than in controls. Mutants for PD-L1 (rs4143815) and PD-1 (rs2227982 and rs7421861) polymorphisms were significantly more common in MM than in HC. Interestingly, PD-L1 (rs4143815) and PD-1 (rs2227982 and rs7421861) variants were linked to higher sPD-L1 and sPD-1 levels, respectively. PD-1/PD-L1 levels are significantly higher in MM patients and could be a promising biomarker for the disease. Variants of PD-L1 and PD-1 are linked to serum-soluble proteins and are associated with the development of MM.
多发性骨髓瘤（MM）是一种以进行性免疫失调为特征的恶性疾病。程序性细胞死亡蛋白 1（PD-1）/程序性死亡配体 1（PD-L1）在 MM 中的重要性已在各种人群中得到证实，但研究仅限于中国队列。在本研究中，我们检查了 PD-1/PDL-1 在大量中国 MM 患者和健康对照者中的作用，以揭示其与 MM 可能存在的关联。本研究纳入了 334 例 MM 患者和 202 例年龄和性别匹配的健康对照者。通过 ELISA 定量检测 PD-1 和 PD-L1 的血清水平。通过流式细胞术评估表达 PD-1 受体的 T 细胞（CD4 和 CD8 T 细胞）的百分比。采用 PCR-RFLP 方法检测 PD-L1（rs4143815）和 PD-1 基因（rs2227981、rs2227982、rs7421861 和 rs11568821）的变异。多发性骨髓瘤患者的 PD-1 和 PDL-1 水平高于健康对照组，表明程序性细胞死亡蛋白 1 及其配体在 MM 的发病机制中具有重要作用。MM 患者表达 PD-1 受体的 T 细胞也明显高于对照组。PD-L1（rs4143815）和 PD-1（rs2227982 和 rs7421861）多态性在 MM 患者中明显更为常见。有趣的是，PD-L1（rs4143815）和 PD-1（rs2227982 和 rs7421861）变异与更高的 sPD-L1 和 sPD-1 水平相关。MM 患者的 PD-1/PD-L1 水平显著升高，可能是该疾病有前途的生物标志物。PD-L1 和 PD-1 的变体与血清可溶性蛋白相关，与 MM 的发生有关。
