原发性肾病综合征患儿血、尿中可溶性程序性死亡受体1和配体1水平及其临床意义

目的检测原发性肾病综合征(PNS)患儿血清及尿液中可溶性程序性死亡受体1(sPD-1)和可溶性程序性死亡配体1(sPD-L1)水平,并探讨其临床意义。方法病例来自苏州大学附属儿童医院2017年7月至2017年11月收住入院的PNS患儿,按照PNS病程分为发作期组(36例)和缓解期组(33例)。选取同时期因入学体检或偏矮偏胖在儿童保健科门诊和内分泌科住院部体检的健康儿童30例为健康对照组。收集血清和尿液标本,采用酶联免疫吸附法(ELISA)检测血清及尿液中sPD-1和sPD-L1水平。Pearson和Spearman相关法分析血清和尿液sPD-1、sPD-L1水平与淋巴细胞亚群、尿微量蛋白水平的相关性。结果PNS缓解期组患儿血清sPD-1含量明显低于健康对照组[1.60(0.48,8.15)ng/ml比7.38(2.15,19.02)ng/ml,P﹤0.01];发作期组患儿尿液sPD-1水平高于缓解期组和健康对照组[1.21(0.61,2.56)比0.51(0.31,0.97)pg/μg,P﹤0.001;1.21(0.61,2.56)比0.82(0.34,1.15)pg/μg,P﹤0.01]。发作期组和缓解期组患儿血清和尿液中sPD-L1水平均高于健康对照组(均P﹤0.001)。发作期组血清sPD-1水平与外周血CD3^+、CD3^+CD4^+、CD3^+CD8^+T细胞计数和CD3^-CD19^+、CD19^+CD23^+B细胞计数呈正相关(r值分别为0.537、0.478、0.454、0.429和0.374;P值分别为0.002、0.008、0.012、0.018和0.042)。发作期组患儿尿液sPD-1水平和24h尿微量白蛋白/体重比值(24hUmAlb/Wt)、尿N乙酰氨基葡萄糖苷酶/尿肌酐比值(UNAG/Cr)及β2微球蛋白/尿肌酐比值(Uβ2MG/Cr)呈正相关(r值分别为0.409、0.588和0.276;P值分别为0.016、0.000和0.032)。结论PNS患儿血清和尿液sPD-1、sPD-L1水平动态变化提示PD-1/PD-L1信号通路可能参与了PNS的发生发展过程。

Clinical significance of sPD-1 and sPD-L1 in serum and urine of children with primary nephrotic syndrome

Objectives To detect the level of soluble programmed death 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in serum and urine of children with primary nephrotic syndrome (PNS), and explore its clinical significance. Methods From July 2017 to November 2017, children with PNS admitted to the Children's Hospital Affiliated to Soochow University were divided into onset group (36 cases) and remission group (33 cases). Thirty healthy children who underwent medical examination for enrollment, undersize or overweight in the outpatient department of pediatric health care and inpatient department of Endocrinology were selected as healthy control group. Serum and urine samples were collected, in which the levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA). The correlation between serum and urine sPD-1, sPD-L1 levels and lymphocyte subsets, urinary protein were analyzed by Pearson and Spearman correlation analysis. Results The level of sPD-1 in serum was lower in remission group than those in healthy control group [1.60(0.48, 8.15) ng/ml vs 7.38(2.15, 19.02) ng/ml, P﹤0.01]. The level of urinary sPD-1 in onset group was higher than that in remission group [1.21(0.61, 2.56) pg/μg vs 0.51(0.31, 0.97) pg/μg, P﹤0.001] and healthy control group [1.21(0.61, 2.56) pg/μg vs 0.82(0.34, 1.15) pg/μg, P﹤0.01]. The levels of sPD-L1 in serum and urine were higher in onset and remission group than those in healthy control group (P﹤0.001). The level of sPD-1 in the serum was positive correlated with the numbers of CD3+, CD3+CD4+, CD3+ CD8+ T lymphocytes and CD3-CD19+, CD19+CD23+ B lymphocytes (r=0.537, 0.478, 0.454, 0.429 and 0.374; P=0.002, 0.008, 0.012, 0.018 and 0.042). The level of sPD-1 in the urine had positive relation with the ratio of 24 hours urinary albumin and weight (24 h UmAlb/Wt), N-acetylglucosaminidase and urinary creatinine (UNAG/Cr) and β2 microglobulin and urinary creatinine (Uβ2MG/Cr) (r=0.409, 0.588 and 0.276; P=0.016, 0.000 and 0.032). Conclusions The dynamic changes of sPD-1 and sPD-L1 in serum and urine suggested that PD-1/PD-L1 signaling pathway is involved in the development process of childhood primary nephrotic syndrome.