Significance of lymphocyte subset detection in immune function evaluation of children with nephrotic syndrome
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摘要: 原发性肾病综合征(primary nephrotic syndrome, PNS)是儿童时期常见的肾小球疾病,也是进展为慢性肾衰竭的主要原因。原发性肾病综合征的发病机制尚未明确,但长期研究证实可能与免疫功能紊乱有关,淋巴细胞亚群作为反映机体免疫功能的指标,对于研究PNS的发病机制及指导治疗、预后都具有意义。几十年前已有研究证实T淋巴细胞亚群异常可能与肾病综合征的发病机制有关,在这之后的许多研究进一步证实T淋巴细胞介导的细胞免疫在PNS发病中的主导作用。对于B淋巴细胞介导的体液免疫,近年来多数文献报道Rituximab(CD20单克隆抗体)用于治疗儿童难治性肾病综合征,尤其是激素依赖型和频繁复发型肾病综合征的患儿,可使其得到显著缓解,提示B淋巴细胞功能的异常可能与儿童原发性肾病综合征的发病有关。NK细胞作为人体的一种免疫细胞,对于PNS患儿的预后也有很大的价值,NK细胞水平较低的患儿更易复发,且激素治疗后NK细胞水平较低的患儿发生感染的风险更高,可以看出NK细胞在PNS的发生、发展中有着重要作用。本文主要对T淋巴细胞亚群、B淋巴细胞及NK细胞进行简要综述,探讨它们与PNS的关系。Abstract: Primary nephrotic syndrome (PNS) is a common glomerular disease in childhood, and it is also the main cause of chronic renal failure. The pathogenesis of PNS remains unclear, but long-term studies have confirmed that it may be related to immune dysfunction. Lymphocyte subsets, an indicator of immune function, are of great significance in studying the pathogenesis, guiding treatment and predicting the prognosis of PNS. Decades ago, studies have confirmed that T lymphocyte subsets may be related to the pathogenesis of nephrotic syndrome. Many studies have also confirmed the dominant role of T lymphocyte-mediated cellular immunity in the pathogenesis of PNS. In recent years, Rituximab (CD20 monoclonal antibody) has been used to treat children with refractory nephrotic syndrome, especially in children with steroid-dependent and frequent relapse nephrotic syndrome. It suggests that the abnormal function of B lymphocytes may be related to the occurrence of childhood PNS. NK cells, a kind of immune cells in the human body, are also of great value for the prognosis of children with PNS. Children with lower NK cell levels are more likely to relapse and are more likely to have the risk of infection after hormone therapy. NK cells play an important role in the occurrence and development of PNS. This article mainly summarises T lymphocyte subsets, B lymphocytes and NK cells, and discusses their relationship with PNS.
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Key words:
- Children /
- Nephrotic syndrome /
- Lymphocyte subsets
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[1] 王卫平, 孙锟, 常立文. 儿科学[M]. 9版. 北京: 人民卫生出版社, 2018: 300-301.WANG W P, SUN K, CHANG L W, Pediatrics[M]. 9th Edition. Beijing: People's Medical Publishing House, 2018: 300-301. [2] 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. doi: 10.3760/cma.j.issn.0578-1310.2017.10.003Chinese Medical Association Pediatrics Branch Nephrology Group. Evidence-based guidelines for the diagnosis and treatment of hormone-sensitive, recurrent/dependent nephrotic syndrome in children (2016)[J]. Chinese Journal of Pediatrics. 2017, 55(10): 729-734. doi: 10.3760/cma.j.issn.0578-1310.2017.10.003 [3] 高洁, 陈朝英, 涂娟, 等. 儿童原发肾病综合征并发急性肾损伤相关因素分析[J]. 中国医刊, 2020, 55(2): 217-220. doi: 10.3969/j.issn.1008-1070.2020.02.030GAO J, TU J, GENG H Y, et al. Analysis of related factors of children with primary nephrotic syndrome complicated with acute kidney injury[J]. Chinese Medical Journal, 2020.55(2): 217-220. doi: 10.3969/j.issn.1008-1070.2020.02.030 [4] 童科珍, 毛建华, 傅海东, 等. 肾病综合征患儿血清细胞因子水平及T细胞亚群变化的临床意义[J]. 中华临床免疫和变态反应杂志, 2016, 10(4): 351-356. https://www.cnki.com.cn/Article/CJFDTOTAL-OZHL201604007.htmDONG K Z, MAO J H, FU H D, et al. Clinical significance of changes in serum cytokines and T cell subsets in children with nephrotic syndrome[J]. Chinese Journal of Clinical Immunology and Allergy, 2016.10(4): 351-356. https://www.cnki.com.cn/Article/CJFDTOTAL-OZHL201604007.htm [5] 刘林娜, 陈荣发, 陈慧, 等. 淋巴细胞亚群检测在儿童肾病综合征患者中的应用价值[J]. 中国卫生检验杂志, 2018, 28(18): 2245-2247. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201818021.htmLIU L N, CHEN R F, CHEN H, et al. Application value of lymphocyte subset detection in children with nephrotic syndrome[J]. Chinese Journal of Health Inspection, 2018.28(18): 2245-2247. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201818021.htm [6] 王军, 袁纯辉, 袁文, 等. 肾病综合征患儿外周血T淋巴细胞亚群、免疫球蛋白、补体表达观察[J]. 山东医药, 2019, 59(6): 79-81. doi: 10.3969/j.issn.1002-266X.2019.06.022WANG J, YUAN C H, YUAN W, et al. Observation on the expression of peripheral blood T lymphocyte subsets, immunoglobulin and complement in children with nephrotic syndrome[J]. Shandong Medicine, 2019.59(6): 79-81. doi: 10.3969/j.issn.1002-266X.2019.06.022 [7] 马玉花, 刘志刚, 王小兰, 等. 原发性肾病综合征患者淋巴细胞亚群和免疫球蛋白变化及价值[J]. 中国卫生工程学, 2020, 19(3): 406-408. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWX202003034.htmMA Y H, LIU Z G, MA X L, et al. Changes and value of lymphocyte subsets and immunoglobulin in patients with primary nephrotic syndrome[J]. China Health Engineering, 2020.19(3): 406-408. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGWX202003034.htm [8] OH G, WALDO A, PAEZ-CRUZ F, et al. Steroid-addociated side effects in patients with primary proteinuric kidney diease[J]. Kidney Int Rep, 2019, 4(11): 1608-1616. doi: 10.1016/j.ekir.2019.08.019 [9] EL MASHAD G M, EL HADY IBRAHIM S A, ABDELNABY S A A, et al. Immunoglobulin G and M levels in childhood nephrotic syndrome: Two centers Egyptian study[J]. Electron Physician, 2017, 9(2): 3728-3732. doi: 10.19082/3728 [10] GUIMARÃES F T L, MELO G E B A, CORDEIRO T M, et al. T-lymphocyte-expressing inflammatory cytokines underlie persistence of proteinuria in children with idiopathic nephrotic syndrome[J]. J Pediatr (Rio J), 2018, 94(5): 546-553. doi: 10.1016/j.jped.2017.08.005 [11] DUECHTING A, PRZYBYLA A, KUERTEN S, et al. Delayed activation kinetics of Th2- and Th17 cells compared to Th1 cells[J]. Cells, 2017, 63(3): 29. [12] YANG X, TANG X, LI T, et al. Circulating follicular T cells are possibly associated with low levels of serum immunoglobulin G due to impaired immunoglobulin class-switch recombination of B cells in children with primairy nephrotic syndrome[J]. Mol Immunol, 2019, 114(1): 162-170. [13] 刘光磊, 杨军, 李成荣. 儿童特发性肾病综合征低IgG血症机制: 哺乳动物雷帕霉素靶蛋白过表达对滤泡辅助性T细胞数量的可能影响[J]. 中华妇幼临床医学杂志(电子版), 2020, 16(2): 171-180. doi: 10.3877/cma.j.issn.1673-5250.2020.02.008LIU G L, YANG J, LI C R, Mechanism of hypoIgGemia in children with idiopathic nephrotic syndrome: the possible effect of mammalian target of rapamycin overexpression on the number of follicular helper T cells[J]. Chinese Journal of Maternal and Child Clinical Medicine, 2020.16(2): 171-179. doi: 10.3877/cma.j.issn.1673-5250.2020.02.008 [14] 曾海江, 黄郁波, 易玲, 等. 原发性肾病综合征患儿T淋巴细胞免疫及细胞因子的临床意义[J]. 中国当代医药, 2020, 27(27): 79-81, 85. doi: 10.3969/j.issn.1674-4721.2020.27.023ZENG H B, HUANG Y J, YI L, Clinical significance of T lymphocyte immunity and cytokines in children with primary nephrotic syndrome[J]. Chinese Contemporary Medicine, 2020.27(27): 79-81, 85. doi: 10.3969/j.issn.1674-4721.2020.27.023 [15] 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(3): e9854. DOI: 10.7717/peerj.9854. [16] WANG L, LI Q, YANG H, et al. The role of Th17/IL-17 in the pathogenesis of primary nephrotic syndrome in children[J]. Kidney Blood Press Res, 2013, 37(4-5): 332-345. doi: 10.1159/000350161 [17] ZHAI S, SUN B, ZHANG Y, et al. IL-17 aggravates renal injury by promoting podocyte injury in children with primary nephrotic syndrome[J]. Exp Ther Med, 2020, 20(1): 409-417. doi: 10.3892/etm.2020.8698 [18] SHUAI L, CHENG Q, SHEN T, et al. CTLA4-Ig Abatacept ameliorates proteinuria by regulating circulating Treg/IL-17 in adriamycin-induced nephropathy rats[J]. Biomed Res lnt, 2020(1): 1-9. [19] ZHANG X M, LIU C Y, SHAO Z H, et al. Advances in the role of helper T cells in autoimmune diseases[J]. Chin Med J (Engl), 2020, 133(8): 968-974. doi: 10.1097/CM9.0000000000000748 [20] MA J, ZHENG B, GOSWAMI S, et al. PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular arcinoma[J]. J Immunother Cancer, 2019, 7(1): 331. doi: 10.1186/s40425-019-0814-7 [21] LIU Y, ZHENG K, LIU Y, et al. Pneumocystis jirovecii pneumonia in patients with nephrotic syndrome: Application of lymphocyte subset analysis in predicting clinical outcomes[J]. Can J Infect Dis Med Microbiol, 2020(1): 4631297. DOI: 10.1155/2020/4631297. [22] 寿晓霞, 刘佳谊, 淋巴细胞亚群、hs-CRP、TGF-β1水平与儿童原发性肾病综合征预后的关系研究[J]. 国际检验医学杂志, 2020, 41(12): 1479-1482. doi: 10.3969/j.issn.1673-4130.2020.12.017CHOU X X, LIU J Y, Relationship between lymphocyte subsets, hs-CRP, TGF-β1 levels and prognosis of children with primary nephrotic syndrome[J]. International Journal of Laboratory Medicine, 2020.41(12): 1479-1482. doi: 10.3969/j.issn.1673-4130.2020.12.017 [23] SCHEINECKER C, GÖSCHL L, BONELLI M, et al. Treg cells in health and autoimmune diseases: New insights from single cell analysis[J]. J Autoimmun, 2020, 110(6): 102376. DOI: 10.1016/j.jaut.2019.102376. [24] TSUJI S, KIMATA T, YAMANOUCHI S, et al. Regulatory T cells and CTLA-4 in idiopathic nephrotic syndrome[J]. Pediatr Int, 2017, 59(5): 643-646. doi: 10.1111/ped.13255 [25] EROGLU F K, ORHAN D, INÖZV M, et al. CD80 expression and infiltrating regulatory T cells in idiopathic nephrotic syndrome of childhood[J]. Pediatr Int, 2019, 61(12): 1250-1256. doi: 10.1111/ped.14005 [26] 冯杏, 赵丽君, 寇敏, 等. 调节性T细胞及其相关细胞因子转化生长因子β1白细胞介素10在儿童激素敏感型原发性肾病综合征发病机制中的作用[J]. 中国药物与临床, 2019, 19(16): 2713-2716. https://www.cnki.com.cn/Article/CJFDTOTAL-YWLC201916004.htmFENG X, ZHAO L J, KOU M, The role of regulatory T cells and their related cytokines transforming growth factor β_1 and interleukin-10 in the pathogenesis of hormone-sensitive primary nephrotic syndrome in children[J]. Chinese Medicine and Clinic, 2019.19(16): 2713-2716. https://www.cnki.com.cn/Article/CJFDTOTAL-YWLC201916004.htm [27] GUIMARÃES F T L, FERREIRA R N, BRITO-MELO G E A, et al. Pediatric patients with steroid-sensitive nephrotic syndrome have higher expression of T regulatory lymphocytes in comparison to steroid-resistant disease[J]. Front Pediatr, 2019, 7(8): 114. [28] WU C, CHEN Z, XIAO S, et al. SGK1 governs the reciprocal development of Th17 and regulatory T cells[J]. Cell Reports, 2018, 22(3): 653-665. doi: 10.1016/j.celrep.2017.12.068 [29] LEE G R. The balance of Th17 versus Treg cells in autoimmunoty[J]. Int J Mol Sci, 2018, 19(3): 730. doi: 10.3390/ijms19030730 [30] 赵丽君, 冯杏, 寇敏, 等. 辅助性T细胞17/调节性T细胞失衡在儿童激素敏感型原发性肾病综合征发病机制中的研究[J]. 中国药物与临床, 2019, 19(3): 391-393. https://www.cnki.com.cn/Article/CJFDTOTAL-YWLC201903022.htmZHAO L J, FENG X, KOU M, The role of helper T cell 17/regulatory T cell imbalance in the pathogenesis of hormone-sensitive primary nephrotic syndrome in children[J]. Chinese Medicine and Clinic, 2019.19(03): 391-393. https://www.cnki.com.cn/Article/CJFDTOTAL-YWLC201903022.htm [31] ZHANG L, YAN J, YANG B, et al. IL-23 activated γδT cells affect Th17 cells and regulatory T cells by secreting IL-21 in children with primary nephrotic syndrome[J]. Scand J Immunol, 2018, 87(1): 36-45. doi: 10.1111/sji.12629 [32] XIA H, WANG F, WANG M, et al. Maresin1 ameliorates acute lung injury induced by sepsis through regulating Th17/Treg balance[J]. Life Sci, 2020, 254(1): 117773. [33] 薛苗, 毛小荣, 陈红, 辅助性T淋巴细胞17/调节性T淋巴细胞比值失衡在免疫性肝损伤大鼠模型中的变化特点[J]. 临床肝胆病杂志, 2020, 36(1): 149-152. doi: 10.3969/j.issn.1001-5256.2020.01.033XUE M, MAO X R, CHEN H, Change characteristics of helper T lymphocyte 17/regulatory T lymphocyte ratio imbalance in a rat model of immune liver injury[J]. Journal of Clinical Hepatobiliary Diseases, 2020.36(01): 149-152. doi: 10.3969/j.issn.1001-5256.2020.01.033 [34] LING C, WANG X, CHEN Z, et al. Altered B-lymphocyte homeostasis in idiopathic nephrotic syndrome[J]. Front Pediatr, 2019, 7(1): 377. [35] COLUCCI M, CARSETTI R, CASCIOLI S, et al. B cell phenotype in pediatric idiopathic nephrotic syndrome[J]. Pediatr Nephrol, 2019, 34(1): 177-181. doi: 10.1007/s00467-018-4095-z [36] 王美秋, 夏正坤, 高春林. 利妥昔单抗在儿童原发性肾病综合征中的应用[J]. 医学研究生学报, 2020, 33(4): 433-437.WANG M Q, The application of rituximab in children with primary nephrotic syndrome[J]. Journal of Postgraduate Medicine, 2020.33(4): 433-437. [37] KARI J, ALHASAN K, ALBANNA A, et al. Rituximab versus cyclophosphamide as first steroid-sparing agent in childhood frequently relapsing and steroid-dependent nephrotic syndrome[J]. Pediatr Nephrol, 2020, 358(8): 1445-1453. [38] BHATIA D, SINHA A, HARI P, et al. Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome[J]. Pediatr Res, 2018, 84(4): 520-526. doi: 10.1038/s41390-018-0088-7 [39] 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(7): 954-958. doi: 10.3969/j.issn.1006-5725.2020.07.024YU P, PENG Q Q, DONG C, et al, Clinical significance of B lymphocyte phenotype in children with hormone-dependent and frequently relapsing nephrotic syndrome[J]. Journal of Practical Medicine, 2020.36(7): 954-958. doi: 10.3969/j.issn.1006-5725.2020.07.024 [40] 陈少艳, 刘基铎, 肖明锋, 等, 淋巴细胞亚群检测在感染性疾病中的应用[J]. 国际检验医学杂志, 2017, 38(2): 206-208. https://www.cnki.com.cn/Article/CJFDTOTAL-GWSQ201702024.htmCHEN S Y, LIU J D, XIAO M F, et al, Application of lymphocyte subset detection in infectious diseases[J]. International Journal of Laboratory Medicine, 2017.38(02): 206-208. https://www.cnki.com.cn/Article/CJFDTOTAL-GWSQ201702024.htm [41] HOOGSTAD-VAN EVERT J, BEKKERS R, OTTEVANGER N, et al. Harnessing natural killer cells for the treatment of ovarian cancer[J]. Gynecol Oncol, 2020, 157(3): 810-816. doi: 10.1016/j.ygyno.2020.03.020 [42] GIANCHECCHI E, DELFINO D V, FIERABRACCI A, et al. NK cells in autoimmune diseases: Linking innate and adaptive immune responses[J]. Autoimmun Rev, 2018, 17(2): 1442-1154. [43] 周晖登, 黄海锋, 唐银琳, 等. NK细胞对激素敏感型肾病综合征患儿预后判断的价值[J]. 现代免疫学, 2019, 39(1): 41-44. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY201901008.htmZHOU H D, HUANG H F, TANG Y L, et al, The prognostic value of NK cells in children with hormone-sensitive nephrotic syndrome[J]. Modern Immunology, 2019.39(1): 41-44. https://www.cnki.com.cn/Article/CJFDTOTAL-SHMY201901008.htm
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