核周型抗中性粒细胞胞浆抗体对儿童系统性红斑狼疮的临床意义

doi:10.12372/jcp.2022.21e1211

摘要/Abstract

摘要：

目的分析核周型抗中性粒细胞胞浆抗体（pANCA）检测对儿童系统性红斑狼疮（SLE）的临床意义。方法回顾性分析2016年1月至2021年7月就诊的SLE患儿的临床资料,对pANCA阳性和阴性患儿的自身抗体相关指标、免疫功能、肾功能及肾脏病理进行分析。结果共纳入191例SLE患儿,女160例、男31例,平均年龄（12.0±3.5）岁。pANCA阳性组81例,其中pANCA（甲醛抗性）阳性26例、pANCA（甲醛敏感）阳性55例;抗髓过氧化物酶（MPO）抗体阳性29例,占pANCA阳性患儿的35.8%。与pANCA阴性组相比,pANCA阳性组患儿血沉较高,Hb较低,自身抗体中抗核抗体、抗双链DNA（dsDNA）抗体、抗干燥综合征抗原 A（SSA）抗体、抗着丝点蛋白B（CENP-B）抗体、抗组蛋白抗体、抗核糖体核蛋白（rRNP）抗体、抗核小体抗体以及抗Ro-52抗体的阳性率均较高,差异有统计学意义（P<0.05）。与pANCA阴性组相比,pANCA阳性组患儿补体C3和C4较低,尿肌酐、尿免疫球蛋白G/尿肌酐（UCr）、α1-微球蛋白/UCr、β1-微球蛋白/UCr、尿微量白蛋白/UCr水平较高,尿隐血和尿蛋白比例较高,差异均有统计学意义（P<0.05）。共112例SLE患儿行肾穿刺活检,与pANCA阴性组相比,pANCA阳性组系膜增生比例较高,肾小球系膜和毛细血管袢的IgG、IgM、IgA、C1q和C3沉积比例较高,差异均有统计学意义（P<0.05）。结论在儿童SLE中,pANCA阳性提示更容易发生肾损伤,病情更严重。

关键词: 系统性红斑狼疮, 抗中性粒细胞胞浆抗体, 肾脏病理, 儿童

Abstract:

Objective To investigate the clinical significance of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in children with systemic lupus erythematosus. Methods The clinical data of SLE children treated from January 2016 to July 2021 were retrospectively analyzed. The autoantibody related indexes, immune function, renal function and renal pathology of pANCA positive and negative children were analyzed. Results A total of 191 SLE children (160 girls and 31 boys) were enrolled, and the average age was (12.0±3.5) years. There were 81 children in pANCA positive group, among whom 26 were formaldehyde-resistant pANCA positive and 55 were formaldehyde-sensitive pANCA positive. Anti-myeloperoxidase (MPO) antibody was positive in 29 children, accounting for 35.8% of pANCA positive children. Compared with pANCA negative group, children in pANCA positive group had higher ESR, lower Hb, and higher positive rates of antinuclear antibody, anti-double-stranded DNA (dsDNA) antibody, anti-Sjögren's-syndrome-related antigen A (SSA) autoantibody, anticentromere protein B (CENP-B) antibody, anti-histone antibody, anti-ribosome ribonucleoprotein (rRNP) antibody, anti-nucleosome antibody and anti-Ro-52 antibody. The differences were statistically significant (P<0.05). Compared with pANCA negative group, pANCA positive group had lower levels of complement C3 and C4, higher levels of urinary creatinine (UCr), urinary immunoglobulin G/UCr, α1-microglobulin/UCr, β1-microglobulin/UCr and urinary microalbumin/UCr, and higher proportion of urinary occult blood and urinary protein, and the differences were statistically significant (P<0.05). A total of 112 children with SLE underwent renal biopsy. Compared with the pANCA negative group, the proportion of mesangial hyperplasia and the deposition proportion of IgG, IgM, IgA, C1q and C3 in glomerular mesangium and capillary loop was higher in the pANCA positive group, and the differences were statistically significant (P<0.05). Conclusions In children with SLE, pANCA positive children are more likely to have renal injury and more severe symptoms.

Key words: systemic lupus erythematosus, antineutrophil cytoplasmic antibody, renal pathology, child

何萍, 沈佳, 徐丹, 王紫燕. 核周型抗中性粒细胞胞浆抗体对儿童系统性红斑狼疮的临床意义[J]. 临床儿科杂志, 2022, 40(10): 739-744.

HE Ping, SHEN Jia, XU Dan, WANG Ziyan. Clinical significance of perinuclear anti-neutrophil cytoplasmic antibody in children with systemic lupus erythematosus[J]. Journal of Clinical Pediatrics, 2022, 40(10): 739-744.

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参考文献 17

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项目	pANCA阴性(n=110)	pANCA阳性(n=81)	统计量	P
WBC[M(P₂₅~P₇₅)]×10⁹/L	6.1(4.1~8.8)	5.6(3.8~8.5)	Z=0.93	0.351
PLT[M(P₂₅~P₇₅)]×10⁹·L^-1	242.5(94.0~315.5)	175.0(80.0~252.0)	Z=1.87	0.061
Hb[M(P₂₅~P₇₅)]/g·L^-1	118.0(111.0~132.0)	102.0(92.0~129.0)	Z=2.25	0.024
CRP[M(P₂₅~P₇₅)]/mg·L^-1	0.4(0.2~2.2)	0.4(0.1~1.7)	Z=0.61	0.540
血沉[M(P₂₅~P₇₅)]/mm·h^-1	8.5(3.5~28.3)	36.0(13.0~70.0)	Z=3.10	0.002
自身抗体阳性[n(%)]
ANA	64(58.2)	77(95.1）	χ²=32.83	<0.001
dsDNA抗体	30(27.2）	64(79.0）	χ²=49.96	<0.001
抗Sm抗体	24(21.8）	26(32.1）	χ²=2.55	0.110
抗SSA抗体	25(22.7）	36(44.4）	χ²=10.12	0.001
抗Scl-70抗体	9(8.2）	3(3.7）	χ²=1.59	0.207
抗CENP-B抗体	0(0.0）	5(6.2）	χ²=4.76	0.029
抗SSB抗体	8(7.3）	8(9.9）	χ²=0.41	0.521
抗Jo-1抗体	0(0.0）	2(2.5）	-	0.179¹⁾
抗U1-nRNP/Sm抗体	30(27.3）	28(34.6）	χ²=1.17	0.279
抗组蛋白抗体	18(16.4）	41(50.6）	χ²=25.64	<0.001
抗rRNP抗体	27(24.6）	31(38.3）	χ²=4.16	0.041
抗核小体抗体	15(13.6）	52(64.2）	χ²=52.37	<0.001
抗Ro-52抗体	28(25.5）	33(40.7）	χ²=5.02	0.025
抗PM-ScL抗体	3(2.7）	3(3.7）	χ²=0.16	0.649
抗PCNA抗体	9(8.2）	8(9.9）	χ²=0.17	0.684
抗AMA-M2抗体	9(8.2）	9(11.1）	χ²=0.47	0.493

项目	pANCA阴性(n=110)	pANCA阳性(n=81)	统计量	P
CD3⁺($\bar{x}±s$)/%	72.5±8.6	72.0±9.8	t=0.26	0.792
CD4⁺($\bar{x}±s$)/%	30.5±7.1	31.5±9.4	t=0.52	0.603
CD8⁺($\bar{x}±s$)/%	36.2±10.9	35.6±9.5	t=0.26	0.796
CD3^-CD19⁺[M(P₂₅~P₇₅)]/%	16.8(12.7~22.9)	17.1(11.7~23.9)	Z=0.21	0.838
CD3^-CD16⁺56⁺[M(P₂₅~P₇₅)] /%	8.1(4.6~10.8)	6.7(3.3~10.0)	Z=1.01	0.315
C3[M(P₂₅~P₇₅)]/g·L^-1	0.9(0.7~1.1)	0.4(0.3~0.7)	Z=4.02	<0.001
C4[M(P₂₅~P₇₅)]/g·L^-1	0.2(0.1~0.2)	0.1(0.0~0.1)	Z=3.94	<0.001
IgA[M(P₂₅~P₇₅)]/g·L^-1	1.9(1.4~2.7)	1.7(1.3~2.4)	Z=0.89	0.376
IgG[M(P₂₅~P₇₅)]/g·L^-1	12.3(10.0~14.9)	14.0(11.1~19.1)	Z=1.55	0.121
IgM[M(P₂₅~P₇₅)]/g·L^-1	1.3(0.9~1.8)	1.1(0.8~1.7)	Z=0.80	0.426
UCr[M(P₂₅~P₇₅)]/mmol·L^-1	7.3(4.5~9.0)	9.0(6.1~11.3)	Z=2.05	0.040
UIgG/UCr[M(P₂₅~P₇₅)]/mg·mmol^-1	0.0(0.0~0.7)	2.1(0.1~16.4)	Z=3.10	0.002
α1-MG/UCr[M(P₂₅~P₇₅)]/mg·mmol^-1	0.6(0.3~1.0)	1.7(0.7~3.0)	Z=3.30	0.001
β1-MG/UCr[M(P₂₅~P₇₅)]/mg·mmol^-1	0.0(0.0~0.1)	0.1(0.0~0.4)	Z=2.34	0.020
U-TRF/UCr[M(P₂₅~P₇₅)]/mg·mmol^-1	0.0(0.0~0.0)	0.0(0.0~7.9)	Z=1.95	0.051
NAG/UCr[M(P₂₅~P₇₅)]/U·mmol^-1	2.3(1.0~3.7)	3.2(1.8~7.2)	Z=2.45	0.014
UMA/UCr[M(P₂₅~P₇₅)]/mg·mmol^-1	2.2(0.6~6.3)	6.5(0.9~30.1)	Z=1.98	0.048
尿隐血阳性[n(%)]	23(20.9)	37(45.7)	χ²=13.28	<0.001
尿蛋白阳性[n(%)]	12(10.9)	24(29.6)	χ²=10.69	0.001

项目	pANCA阴性(n=63)	pANCA阳性(n=49)	χ²值	P
系膜增生	11(17.5 )	22(44.9)	9.98	0.002
毛细血管袢改变(受挤压和开放不良)	2(3.2)	3(6.1)	0.56	0.454
毛细血管壁基底膜增厚	1(1.6)	6(12.2)	3.68	0.055
新月体形成	0(0.0)	3(6.1)	1.96	0.161
免疫标记
IgG	5(7.9)	19(38. 8)	15.60	<0.001
IgM	7(11.1)	22(44.9)	16.40	<0.001
IgA	4(6.4)	19(38. 8)	17.76	<0.001
C1q	6(9.5)	20(40.8)	15.14	<0.001
C3	6(9.5)	22(44.9)	18.40	<0.001