周围血程序性死亡分子-配体2 (sPD-L2)在系统性红斑狼疮中的水平变化及临床意义
Changes in the Levels of Soluble Programmed Death Molecule-Ligand 2 (sPD-L2) in the Peripheral Blood of Systemic Lupus Erythematosus and Their Clinical Significance
摘要: 系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种自身免疫性疾病,发病机制仍不明确。初步探讨sPD-L2在SLE患者外周血清中的表达水平变化及临床意义。选择SLE患者101例,类风湿性关节炎(rheumatoid arthritis, RA)患者26例和健康体检者(healthy control, HC) 32例,收集患者的临床资料,抽取周围静脉血,应用ELISA方法检测外周血清中sPD-L2表达水平,根据数据特点和研究目的,采用Mann-Whitney U检验、χ2检验或Spearman相关分析法,比较分析其与SLE常见临床表现及实验室指标的关系。结果:1) 与健康对照组比较,SLE患者周围血中sPD-L2表达显著升高(28.04 ± 3.68 pg/mL vs 7.59 ± 2.07 pg/mL, P < 0.0001)。2) 与RA患者组相比,SLE患者血清中sPD-L2表达显著升高(28.04 ± 3.68 pg/mL vs 23.07 ± 3.39 pg/mL, P < 0.0001)。3) SLE患者中,sPD-L2与年龄(r = 0.296, P = 0.003),病程(r = −0.245, P = 0.014),浆膜炎(r = 0.208, P = 0.038)、SLEDAI-2K (r = 0.223, P = 0.026)、抗dsDNA增高(r = 0.205, P = 0.040)、低补体血症(r = 0.196, P = 0.068)、胸膜炎(r = 0.253, P = 0.011)、脓尿(r = 0.271, P = 0.006)、CRP (r = 0.211, P = 0.036)呈正相关关系,而与eGFR呈现出负相关关系(r = −0.360, P = 0.002)。结论:1) 与健康和RA患者人群比较,SLE患者周围血中sPD-L2的表达水平,不仅显著高于健康人群,且显著高于RA患者。2) SLE患者周围血中sPD-L2表达水平与SLE疾病活动度成正相关,可能成为临床判断SLE病情活动程度的潜在生物标志物。
Abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease whose pathogenesis remains unclear. To preliminarily investigate the changes in the expression level of sPD-L2 in the peripheral serum of SLE patients and its clinical significance, a total of 101 patients with SLE, 26 patients with rheumatoid arthritis (RA) and 32 healthy control (HC) patients were selected, the clinical data of the patients were collected, peripheral venous blood was drawn, and the expression levels of sPD-L2 in peripheral serum were detected by ELISA. According to the characteristics of the data and the purpose of the study, it is adopted that Mann-Whitney U test, chi-square test or Spearman correlation analysis were used to compare and analyze their relationship with common clinical manifestations and laboratory indicators of SLE. Results: 1) Compared with the healthy control group, the expression of sPD-L2 in the peripheral blood of SLE patients was significantly increased (28.04 ± 3.68 pg/mL vs 7.59 ± 2.07 pg/mL, P < 0.0001). 2) Compared with RA patients, the expression of sPD-L2 in serum was significantly increased in SLE patients (28.04 ± 3.68 pg/mL vs 23.07 ± 3.39 pg/mL, P < 0.0001). 3) In SLE patients, sPD-L2 was significantly associated with age (r = 0.296, P = 0.003), course of disease (r = −0.245, P = 0.014), serositis (r = 0.208, P = 0.038), SLEDAI-2K (r = 0.223, P = 0.026), increased anti-dsDNA (r = 0.205, P = 0.040), hypocomplementemia (r = 0.196, P = 0.068), and pleurisy (r = 0.253, P = 0.011), pyuter (r = 0.271, P = 0.006), and CRP (r = 0.211, P = 0.036) were positively correlated, while eGFR was negatively correlated (r = −0.360, P = 0.002). Conclusions: 1) Compared with healthy and RA patients, the expression level of sPD-L2 in the peripheral blood of SLE patients was not only significantly higher than that of healthy people, but also significantly higher than that of RA patients. 2) The expression level of sPD-L2 in the peripheral blood of SLE patients is positively correlated with SLE disease activity, which may become a potential biomarker for clinical judgment of SLE disease activity.
文章引用:周东青, 帅宗文. 周围血程序性死亡分子-配体2 (sPD-L2)在系统性红斑狼疮中的水平变化及临床意义[J]. 临床医学进展, 2024, 14(5): 1211-1222. https://doi.org/10.12677/acm.2024.1451543

参考文献

[1] D’Cruz, D.P., Khamashta, M.A. and Hughes, G.R. (2007) Systemic Lupus Erythematosus. Lancet, 369, 587-596. [Google Scholar] [CrossRef
[2] Francisco, L.M., Sage, P.T. and Sharpe, A.H. (2010) The PD-1 Pathway in Tolerance and Autoimmunity. Immunological Reviews, 236, 219-242. [Google Scholar] [CrossRef
[3] Nielsen, C., Ohm-Laursen, L., Barington, T., et al. (2005) Alternative Splice Variants of the Human PD-1 Gene. Cellular Immunology, 235, 109-116. [Google Scholar] [CrossRef] [PubMed]
[4] Onlamoon, N., Rogers, K., Mayne, A.E., et al. (2008) Soluble PD-1 Rescues the Proliferative Response of Simian Immunodeficiency Virus-Specific CD4 and CD8 T Cells during Chronic Infection. Immunology, 124, 277-293. [Google Scholar] [CrossRef] [PubMed]
[5] Sugiura, D., Shimizu, K., Maruhashi, T., et al. (2021) T-Cell-Intrinsic and-Extrinsic Regulation of PD-1 Function. International Immunology, 33, 693-698. [Google Scholar] [CrossRef] [PubMed]
[6] Zhang, K., Kong, X., Li, Y., et al. (2022) PD-1/PD-L1 Inhibitors in Patients with Preexisting Autoimmune Diseases. Frontiers in Pharmacology, 13, 854967. [Google Scholar] [CrossRef] [PubMed]
[7] Chen, Y., Wang, Q., Shi, B., et al. (2011) Development of a Sandwich ELISA for Evaluating Soluble PD-L1 (CD274) in Human Sera of Different Ages as Well as Supernatants of PD-L1 Cell Lines. Cytokine, 56, 231-238. [Google Scholar] [CrossRef] [PubMed]
[8] Yanaba, K., Hayashi, M., Yoshihara, Y., et al. (2016) Serum Levels of Soluble Programmed Death-1 and Programmed Death Ligand-1 in Systemic Sclerosis: Association with Extent of Skin Sclerosis. The Journal of Dermatology, 43, 954-957. [Google Scholar] [CrossRef] [PubMed]
[9] Greisen, S.R., Kragstrup, T.W., Thomsen, J.S., et al. (2022) The Programmed Death-1 Pathway Counter-Regulates Inflammation-Induced Osteoclast Activity in Clinical and Experimental Settings. Frontiers in Immunology, 13, 773946. [Google Scholar] [CrossRef] [PubMed]
[10] Onuora, S. (2020) EULAR Updates Its RA Management Recommendations. Nature Reviews Rheumatology, 16, 128. [Google Scholar] [CrossRef] [PubMed]
[11] Zhang, X., Lu, H., Peng, L., et al. (2022) The Role of PD-1/PD-Ls in the Pathogenesis of IgG4-Related Disease. Rheumatology (Oxford), 61, 815-825. [Google Scholar] [CrossRef] [PubMed]
[12] Fukasawa, T., Yoshizaki, A., Ebata, S., et al. (2017) Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis. Arthritis & Rheumatology, 69, 1879-1890. [Google Scholar] [CrossRef] [PubMed]
[13] Király, Z., Nagy, E., Bokor, L., et al. (2023) The Possible Clinical Significance of a Decreased Serum Level of Soluble PD-L1 in Discoid Lupus Erythematosus, But Not in Subacute Cutaneous Lupus Erythematosus: A Pilot Study. Journal of Clinical Medicine, 12, 5648. [Google Scholar] [CrossRef] [PubMed]
[14] Du, Y., Nie, L., Xu, L., et al. (2020) Serum Levels of Soluble Programmed Death-1 (sPD-1) and Soluble Programmed Death Ligand 1 (sPD-L1) in Systemic Lupus Erythematosus: Association with Activity and Severity. Scandinavian Journal of Immunology, 92, e12884. [Google Scholar] [CrossRef] [PubMed]
[15] Hirahara, S., Katsumata, Y., Kawasumi, H., et al. (2020) Serum Levels of Soluble Programmed Cell Death Protein 1 and Soluble Programmed Cell Death Protein Ligand 2 Are Increased in Systemic Lupus Erythematosus and Associated with the Disease Activity. Lupus, 29, 686-696. [Google Scholar] [CrossRef] [PubMed]