儿童原发膜性肾病肾小球C1q或IgA沉积的意义探讨

C1q or IgA deposition in glomeruli of children with primary membranous nephropathy

目的探讨儿童原发膜性肾病(PMN)肾小球C1q或IgA沉积与临床和病理表现的关系。方法回顾性总结并分析2012年12月至2020年12月北京大学第一医院儿科诊断的33例PMN患儿临床及病理表现[肾组织磷脂酶A2受体(PLA2R)抗原、IgG亚型检测]、血清抗PLA2R抗体及治疗反应等资料。分别根据PLA2R检测结果、肾脏病理表现、是否有C1q沉积、是否有IgA沉积分别分为PLA2R相关组和非PLA2R相关组、典型PMN组和不典型PMN组、C1q沉积组和无C1q沉积组、IgA沉积组和无IgA沉积组。组间比较采用t检验、Mann-Whitney U检验或Fisher确切概率法。结果33例PMN患儿中男20例、女13例,起病年龄11(8,13)岁,临床表现为肾病水平蛋白尿者32例。病程4.6(2.1,11.6)个月时行肾活检,28例(85%)在肾活检前接受糖皮质激素和(或)免疫抑制剂治疗。PLA2R相关组20例(61%),非PLA2R相关组13例(39%)。与非PLA2R相关组相比,PLA2R相关组发病年龄偏大[12(10,13)比7(3,12)岁,Z=-2.52,P=0.011]、前驱感染率低[45%(9/20)比11/13,P=0.032]、自发缓解率低(0比4/13,P=0.017)。肾组织PLA2R抗原阳性与肾脏IgG4沉积为主或共沉积(13/17比5/15)以及肾活检时低白蛋白水平[(25±6)比(29±7)g/L,t=2.14]均显著相关(P=0.031、0.041)。肾脏病理表现为典型PMN者12例、不典型PMN者21例,两组间临床及肾脏病理表现差异均无统计学意义(均P>0.05)。肾小球C1q沉积者10例(32%),其肾活检前病程短于无C1q沉积者[1.8(0.8,5.9)比6.0(2.5,22.3)个月,Z=-2.27,P=0.023];肾小球IgA沉积者12例(36%),其肾活检前病程、临床和病理表现与无IgA沉积者间差异均无统计学意义(均P>0.05)。结论伴或不伴肾小球C1q或IgA沉积不影响PMN患儿的临床表现、肾组织PLA2R和IgG亚型分布以及治疗反应。

Objective To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy(PMN)in children.Methods The clinical and pathological manifestations including(phospholipase A2 receptor,PLA2R)and IgG subclasses staining in renal biopsies,serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed.According to results of PLA2R test and findings renal pathological,the patients were divided into PLA2R-related group and non-PLA2R-related group,typical MN group and atypical MN group,C1q deposit group and non-C1q deposit group,as well as IgA deposit group and non-IgA deposit group respectively.T-test,Mann-Whitney U test and Fisher′s exact probability test were used for comparison between the groups.Results Among the 33 children with PMN,there were 20 males and 13 females,of that the age of onset was 11(8,13)years,and 32 patients had nephrotic level proteinuria.Renal biopsies were performed at 4.6(2.1,11.6)months after onset,and 28 patients(85%)received glucocorticoid or immunosuppressive therapy prior to renal biopsy.There were 20 cases(61%)with PLA2R-related MN and 13 cases(39%)with non-PLA2R-related MN.Compared with the non-PLA2R-related group,the PLA2R-related group had an older age of onset(12(10,13)vs.7(3,12)years,Z=-2.52,P=0.011),a lower preceding infection rate(45%(9/20)vs.11/13,P=0.032)and lower spontaneous remission rate(0 vs.4/13,P=0.017).Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4(13/17 vs.5/15,P=0.031)and low albumin levels at renal biopsy((25±6)vs.(29±7)g/L,t=2.14,P=0.041).There were 12 patients with typical PMN and 21 patients with atypical PMN,and no significant difference in clinical and pathological manifestations was found between these 2 groups(all P>0.05).There were 10 cases(32.3%)with glomerular C1q deposition,and their disease course before renal biopsy was significantly shorter than those without C1q deposition(1.8(0.8,5.9)vs.6.0(2.5,22.3)months,Z=-2.27,P=0.023).Twelve cases(36.4%)had glomerular IgA deposition,and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition(all P>0.05).Conclusion Glomerular C1q or IgA deposition may not affect the clinical manifestations,glomerular PLA2R and IgG subclasses staining pattern,or the response to treatment of PMN in children.