滤泡辅助性T细胞及半乳糖缺乏的IgA_(1)在儿童过敏性紫癜发病机制中的意义

The significance of follicular helper T cells and galactose-deficient IgA_(1) in the pathogenesis of Henoch-Schönlein purpura in children

目的探讨滤泡辅助性T(follicular helper T,Tfh)细胞和半乳糖缺乏的IgA1(galactose-deficient IgA1,Gd-IgA1)在儿童过敏性紫癜(Henoch-Schönlein purpura,HSP)及紫癜性肾炎(Henoch-Schönlein purpura nephritis,HSPN)发生发展中的作用及二者之间相关性。方法选取初发HSP患儿62例,根据是否合并肾脏损害分为HSP组(32例)和紫癜性肾炎(HSPN)组(30例)。另选取20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^(+)PD-1^(+))比例。采用免疫比浊法检测血清IgA表达水平、采用ELISA法检测血清Gd-IgA1表达水平。结果(1)HSP组和HSPN组患儿外周血中Tfh细胞比例、血清Gd-IgA1的表达水平较健康对照组显著升高(P<0.01),HSPN组较HSP组明显增高(P<0.05)。(2)HSPN组中,肾脏病理Ⅲ级及以上患儿、大量蛋白尿患儿外周血Tfh细胞比例、血清Gd-IgA1表达水平分别较肾脏病理Ⅲ级以下患儿、非大量蛋白尿患儿明显升高(P<0.01)。(3)健康对照组儿童外周血Tfh细胞比例与血清Gd-IgA1水平、血清IgA及Gd-IgA1水平均呈正相关关系(P<0.05),HSP组及HSPN组患儿外周血Tfh细胞比例与血清Gd-IgA1水平、血清IgA及Gd-IgA1水平均呈非正相关关系(P>0.05)。结论Tfh细胞过度活化、血清Gd-IgA1水平增高可能是HSP/HSPN发病机制之一,二者升高的程度与疾病的活动度及严重程度可能相关。Tfh细胞可能导致Gd-IgA1生成增加的机制有待进一步研究。

Objective To investigate the role of follicular helper T(Tfh)cells and galactose deficiency IgA1(Gd-IgA1)in the children that were suffering from Henoch-Schönlein purpura(HSP)and Henoch-Schönlein purpura nephritis(HSPN)and the correlation between them.Methods According to the presence or absence of renal injury,62 children with HSP were divided into HSP group with 32 children and HSPN group with 30 children.Twenty children who underwent physical examination at outpatients were known as the healthy control group.Flow cytometry was used to measure the proportion of Tfh(CD4+CXCR5+PD-1+)in peripheral blood.Immunoturbidimetry and ELISA were used to measure the serum levels of IgA1 and Gd-IgA1 respectively.Results(1)The proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA1 in both HSP group and HSPN group had significantly increased than those in healthy control group(P<0.01).Compared result of the HSPN group with HSP group,the proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA1 in HSPN group were higher than that in HSP group(P<0.05).(2)In the HSPN group,the proportion of peripheral blood Tfh cells and the serum levels of Gd-IgA1 in group of renal pathology≥gradeⅢand heavy proteinuria were significantly elevated compared with group of renal pathology<gradeⅢand non-heavy proteinuria(<0.01).(3)In the healthy control group,the serum levels of Gd-IgA1 was positively correlated with the proportion of Tfh cells in peripheral blood and the serum levels of Gd-IgA1(P<0.05).Conversely,a non-positive correlation was shown in HSP and HSPN groups(P>0.05).Conclusion The excessive activation of Tfh cells and the serum levels of Gd-IgA1 may be one of the pathogenesis of HSP/HSPN,the degree of increment of the two factors may be related to the activity and severity of the disease.The mechanism of Tfh cells potentially leading to an increase of Gd-IgA1 production requires further study.