PDF(1617 KB)
PDF(1617 KB)
PDF(1617 KB)
滤泡辅助性T细胞及半乳糖缺乏的IgA1在儿童过敏性紫癜中的表达及意义
Expression and significance of follicular helper T cells and galactose-deficient IgA1 in children with Henoch-Schönlein purpura
目的 探讨滤泡辅助性T（Tfh）细胞和半乳糖缺乏的IgA1（Gd-IgA1）在儿童过敏性紫癜（HSP）发病机制中的作用及两者之间的相关性。方法 选取初发HSP患儿36例，根据是否发生紫癜性肾炎（HSPN）分为HSPN组（11例）和非HSPN组（25例）。另选取15例门诊体检儿童作为健康对照组。采用流式细胞术检测外周血中Tfh细胞（CD4+CXCR5+ICOS+）比例。采用ELISA法检测外周血中IL-21、IL-6、血清IgA1、血清Gd-IgA1表达水平。采用Pearson相关分析法分析HSP组患儿血清Gd-IgA1浓度与Tfh细胞比例及其相关因子的相关性。结果 HSPN和非HSPN组患儿外周血Tfh细胞比例及IL-21、IL-6表达水平较健康对照组升高（P < 0.05），HSPN组上述指标较非HSPN组亦明显上升（P < 0.05）。HSPN和非HSPN组患儿血清中IgA1、Gd-IgA1表达水平较健康对照组升高（P < 0.05），HSPN组患儿血清IgA1和Gd-IgA1水平较非HSPN组亦明显升高（P < 0.05）。HSP组患儿血清Gd-IgA1水平与Tfh细胞比例及IL-21、IL-6水平均呈显著正相关关系（P < 0.05）。结论 Tfh细胞及其相关细胞因子和血清Gd-IgA1共同参与HSP/HSPN的发生。Tfh细胞可能介导了Gd-IgA1生成增加。
Objective To study the role of follicular helper T (Tfh) cells and galactose-deficient IgA1 (Gd-IgA1) in the pathogenesis of childhood Henoch-Schönlein purpura (HSP) and the correlation between them. Methods A total of 36 children with newly-diagnosed HSP were enrolled. They were divided into two groups:HSP nephritis (HSPN) group with 11 children and non-HSPN group with 25 children according to the presence or absence of HSPN. Another 15 children who underwent physical examination at the outpatient service were enrolled as the healthy control group. Flow cytometry was used to measure the proportion of Tfh cells (CD4+CXCR5+ICOS+) in peripheral blood. ELISA was used to measure the levels of interleukin-21 (IL-21) and interleukin-6 (IL-6) in peripheral blood and the serum levels of IgA1 and Gd-IgA1. A Pearson correlation analysis was used to investigate the correlation of serum Gd-IgA1 concentration with Tfh cells and related factors expression in the children with HSP. Results Both the HSPN and non-HSPN groups had significantly higher proportion of Tfh cells and expression levels of IL-21 and IL-6 in peripheral blood than the healthy control group (P < 0.05). The HSPN group had significant increases in the above indices compared with the non-HSPN group (P < 0.05). Both the HSPN and non-HSPN groups had significantly higher serum levels of IgA1 and Gd-IgA1 than the healthy control group (P < 0.05). The HSPN group had significantly higher serum levels of IgA1 and Gd-IgA1 than the non-HSPN group (P < 0.05). In the children with HSP, serum Gd-IgA1 level was positively correlated with Tfh cells proportion and IL-21 and IL-6 levels (P < 0.05). Conclusions Tfh cells and related cytokines and serum Gd-IgA1 are involved in the development of HSP/HSPN. Tfh cells may mediate the increased production of Gd-IgA1.
过敏性紫癜 / 辅助性T细胞 / 半乳糖缺乏的IgA1 / 细胞因子 / 儿童
Henoeh-Schönlein purpura / Helper T cell / Galactose-deficient IgA1 / Cytokine / Child
[1] Pohl M. Henoch-Schönlein purpura nephritis[J]. Pediatr Nephrol, 2015, 30(2):245-252.
[2] Trnka P. Henoch-Schönlein purpura in children[J]. J Paediatr Child Health, 2013, 49(12):995-1003.
[3] Delbet JD, Hogan J, Aoun B, et al. Clinical outcomes in children with Henoch-Schönlein purpura nephritis without crescents[J]. Pediatr Nephrol, 2017, 32(7):1193-1199.
[4] Xia Y, Mao J, Chen Y, et al. Clinical outcomes in children with Henoch-Schönlein purpura nephritis grade IIIa or IIIb[J]. Pediatr Nephrol, 2011, 26(7):1083-1088.
[5] Chen O, Zhu XB, Ren H, et al. The imbalance of Th17/Treg in Chinese children with Henoch-Schönlein purpura[J]. Int Immunopharmacol, 2013, 16(1):67-71.
[6] 孙大庆, 张秋业, 董增义, 等. 过敏性紫癜病儿树突细胞分泌白细胞介素-12水平与TH1/TH2的变化[J]. 中国当代儿科杂志, 2006, 8(4):307-310.
[7] Crotty S. Follicular helper CD4 T cells (TFH)[J]. Annu Rev Immunol, 2011, 29:621-663.
[8] Kiryluk K, Moldoveanu Z, Sanders JT, et al. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis[J]. Kidney Int, 2011, 80(1):79-87.
[9] Kawasaki Y. The pathogenesis and treatment of pediatric Henoch-Schönlein purpura nephritis[J]. Clin Exp Nephrol, 201l, 15(5):648-657.
[10] 中华医学会儿科学分会肾脏学组. 紫癜性肾炎诊治循证指南(2016)[J]. 中华儿科杂志, 2017, 55(9):647-651.
[11] 王春美, 罗源, 王颖超, 等. 滤泡辅助性T细胞和滤泡调节性T细胞在儿童过敏性紫癜发病中的作用[J]. 中国当代儿科杂志, 2015, 17(10):1084-1087.
[12] Zhang Z, Zhao S, Zhang L, et al. A higher frequency of CD4(+)CXCR5(+) T follicular helper cells in patients with newly diagnosed Henoch-Schönlein purpura nephritis[J]. Int Immunopharmacol, 2016, 32:8-15.
[13] Ettinger R, Sims GP, Fairhurst AM, et al. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells[J]. J Immunol, 2005, 175(12):7867-7879.
[14] Pène J, Gauchat JF, Lécart S, et al. Cutting edge:IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells[J]. J Immunol, 2004, 172(9):5154-5157.
[15] Knoppova B, Reily C, Maillard N, et al. The origin and activities of IgA1-containing immune complexes in IgA nephropathy[J]. Front Immunol, 2016, 7:117.
[16] Suzuki H, Fan R, Zhang Z, et al. Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity[J]. J Clin Invest, 2009, 119(6):1668-1677.
[17] Ebefors K, Liu P, Lassén E, et al. Mesangial cells from patients with IgA nephropathy have increased susceptibility to galactose-deficient IgA1[J]. BMC Nephrol, 2016, 17:40.
[18] 康志娟, 刘波, 李志辉, 等. 半乳糖缺陷IgA1在儿童紫癜性肾炎早期诊断中的意义[J]. 中国当代儿科杂志, 2019, 21(2):172-175.
[19] Dullaers M, Li D, Xue Y, et al. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts[J]. Immunity, 2009, 30(1):120-129.
[20] Suzuki H, Raska M, Yamada K, el al. Cytokines alter IgA1 O-glycosylation by dysregulating C1GalT1 and ST6GalNAc-II enzymes[J]. J Biol Chem, 2014, 289(8):5330-5339.
[21] Davin JC, Coppo R. Henoch-Schönlein purpura nephritis in children[J]. Nat Rev Nephrol, 2014, 10(10):563-573.
