Abstract:Objective To investigate the levels of serum soluble programmed death receptor 1(sPD-1) and soluble programmed death protein ligand 1(sPD-L1) in children with frequent relapse of primary nephrotic syndrome and their clinical correlation. Methods A total of 44 patients were included in this study. they were divided into a frequent relapsing nephrotic syndrome (FRNS) group and a non-frequently relapsing nephrotic syndrome (NFRNS) group according to the frequency of recurrence during the course.24 healthy children were served as normal control; blood samples were collected at different time points before and after GC treatment in each group, including before treatment, stable period after treatment, and initial recurrence after treatment; ELISA was adopted to detect serum sPD-1 and sPD-L1. Results Before GC treatment: The levels of sPD-1 and sPD-L1 in the two study groups were higher than those in the control group, and the levels of sPD-L1 in the FRNS group were higher than those in the NFRNS group. After GC treatment: The levels of sPD-1 and sPD-L1 in children in the NFRNS group were not significantly different from those in the normal control group. The levels of sPD-1 and sPD-L1 in children in the FRNS group were higher than those in the control group. The levels of sPD-1 and sPD-L1 in children in the FRNS group were higher than those in the NFRNS group. Compared with before treatment: The levels of sPD-1 and sPD-L1 in FRNS group and NFRNS group were lower than those in the same group before treatment. Before GC treatment in FRNS group, the level of sPD-L1 was negatively correlated with CD19+B cells and NK cells, and the level of sPD-1 was positively correlated with sPD-L1 and CD3+T cells. Conclusion The high level of sPD-L1 and sPD-L1 before and after GC treatment may be related to the frequent recurrence of PNS disease; Serum sPD-1 and sPD-L1 may participate in frequent activity of the PNS disease by affecting the lymphocyte system and antagonizing GC effects.
石梦月, 关凤军. 频繁复发肾病综合征患儿外周血sPD-1和sPD-L1水平及相关性研究[J]. 湖南师范大学学报(医学版), 2023, 20(2): 84-88.
SHI Mengyue, GUAN Fengjun. Study on the level and correlation of sPD-1 and sPD-L1 in peripheral blood of children with frequent relapsing nephrotic syndrome. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(2): 84-88.
[1] Teh YM, Lim SK, Jusoh N, et al.CD80 Insights as Therapeutic Target in the Current and Future Treatment Options of Frequent-Relapse Minimal Change Disease[J]. Biomed Res Int, 2021, 2021: 6671552. [2] Stangou M, Spartalis Μ, Daikidou DV, et al.Impact of Τh1 and Τh2 cytokines in the progression of idiopathic nephrotic syndrome due to focal segmental glomerulosclerosis and minimal change disease[J]. J Nephropathol, 2017, 6: 187-195. [3] Kitchlu A, Fingrut W, Avila-Casado C, et al.Nephrotic Syndrome With Cancer Immunotherapies: A Report of 2 Cases[J]. Ame J Kidney Dis, 2017, 70(4): 581-585. [4] Okoye IS, Xu L, Walker J, et al.The glucocorticoids prednisone and dexamethasone differentially modulate T cell function in response to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade[J]. Cancer Immunol Immunother, 2020, 69: 1423-1436. [5] 中华医学会儿科学分会肾脏学组. 儿童激素敏感、复发/依赖肾病综合征诊治循证指南 (2016)[J]. 中华儿科杂志, 2017, 55(10): 729-734. [6] Zotta F, Vivarelli M, Emma F.Update on the treatment of steroid-sensitive nephrotic syndrome[J]. Pediatr Nephrol, 2022, 37: 303-314. [7] Chan EY, Yu ELM, Angeletti A, et al.Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study[J]. J Am Soc Nephrol, 2022, 33: 1193-1207. [8] Tsuji S, Akagawa S, Akagawa Y, et al.Idiopathic nephrotic syndrome in children: role of regulatory T cells and gut microbiota[J]. Pediatr Res, 2021, 89: 1185-1191. [9] Li J, Niu J, Min W, et al.B7-1 mediates podocyte injury and glomerulosclerosis through communication with Hsp90ab1-LRP5-β-catenin pathway[J]. Cell Death Differ, 2022, 29: 2399-2416. [10] Chen P, Chen Y, Jiang M, et al.Usefulness of the cytokines expression of Th1/Th2/Th17 and urinary CD80 excretion in adult-onset minimal change disease[J]. Peer J, 2020, 8: e9854. [11] Tsuji S, Akagawa S, Akagawa Y, et al.Idiopathic nephrotic syndrome in children: role of regulatory T cells and gut microbiota[J]. Pediatr Res, 2021, 89: 1185-1191. [12] Khan M, Zhao Z, Arooj S, et al.Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy[J]. Front Immunol, 2020, 11: 587460. [13] Bailly C, Thuru X, Quesnel B.Soluble Programmed Death Ligand-1(sPD-L1): A Pool of Circulating Proteins Implicated in Health and Diseases[J]. Cancers (Basel), 2021, 13(12): 3034 . [14] Wu Q, Jiang L, Li SC, et al.Small molecule inhibitors targeting the PD-1/PD-L1 signaling pathway[J]. Acta Pharmacol Sin, 2021, 42(1): 1-9. [15] Schoop R, Wahl P, Le Hir M, et al.Suppressed T-cell activation by IFN-gamma-induced expression of PD-L1 on renal tubular epithelial cells[J]. Nephrol Dial Transplantat, 2004, 19(11): 2713-2720. [16] Starke A, Lindenmeyer MT, Segerer S, et al.Renal tubular PD-L1(CD274) suppresses alloreactive human T-cell responses[J]. Kidney Int, 2010, 78: 38-47. [17] Kasagi S, Kawano S, Okazaki T, et al.Anti-programmed cell death 1 antibody reduces CD4+PD-1+ T cells and relieves the lupus-like nephritis of NZB/W F1 mice[J]. J Immunol, 2010, 184(5): 2337-2347. [18] Neumann K, Ostmann A, Breda PC, et al.The co-inhibitory molecule PD-L1 contributes to regulatory T cell-mediated protection in murine crescentic glomerulonephritis[J]. Sci Rep, 2019, 9(1): 2038. [19] Kitchlu A, Fingrut W, Avila-Casado C, et al.Nephrotic Syndrome With Cancer Immunotherapies: A Report of 2 Cases[J]. Am J Kidney Dis, 2017, 70: 581-585. [20] Kitchlu A, Jhaveri KD, Wadhwani S, et al.A Systematic Review of Immune Checkpoint Inhibitor-Associated Glomerular Disease[J]. Kidney Int Rep, 2021, 6: 66-77. [21] Mayoux M, Roller A, Pulko V, et al. Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy[J]. Sci Transl Med, 2020, 12(534): eaav7431. [22] Cara-Fuentes G, Venkatareddy M, Verma R, et al.Glomerular endothelial cells and podocytes can express CD80 in patients with minimal change disease during relapse[J]. Pediatr Nephrol, 2020, 35(10): 1887-1896. [23] 于跑, 彭倩倩, 董晨, 等. B淋巴细胞表型在激素依赖及频繁复发肾病综合征患儿的临床意义[J]. 实用医学杂志, 2020, 36: 954-958. [24] Fribourg M, Cioni M, Ghiggeri G, et al.CyTOF-Enabled Analysis Identifies Class-Switched B Cells as the Main Lymphocyte Subset Associated With Disease Relapse in Children With Idiopathic Nephrotic Syndrome[J]. Front Immunol, 2021, 12: 726428. [25] Li ZH, Xia TH, Duan CR, et al.[Significance of trace deposition of immunoglobulin M in glomerular mesangium in children with minimal change nephrotic syndrome][J]. Zhongguo Dang Dai Er Ke Za Zhi, 2015, 17: 222-226. [26] Yesmin A, Hossain MA, Islam MN, et al.Comparative Study of Serum IgE Level in Frequent Relapse and Infrequent Relapse Nephrotic Syndrome in Children[J]. Mymensingh Med J, 2023, 32(1): 22-27.