可溶性白介素2受体和肿瘤坏死因子α对狼疮性肾炎活动度的预测价值

doi:10.3969/j.issn.1674-8115.2021.01.009

摘要/Abstract

摘要：

目的·研究血清可溶性白介素2受体（soluble interleukin-2 receptor，sIL-2R）和肿瘤坏死因子α（tumor necrosis factor-α，TNF-α）水平与狼疮性肾炎（lupus nephritis，LN）病情的相关性及对LN活动度的预测价值。方法·采用横断面研究，收集2018年1月—12月于上海交通大学医学院附属仁济医院东院就诊的LN患者40例及健康者68例（对照组），收集其临床相关指标并检测血清sIL-2R和TNF-α。比较LN患者和对照组血清sIL-2R和TNF-α水平，并采用Spearman秩相关分析评价LN患者sIL-2R和TNF-α与临床指标的相关性。此外，将LN患者分为活动组和非活动组，比较两者临床指标的差异，采用多因素Logistic回归分析LN活动度的预测因素，并用受试者工作特征（receiver operating characteristic，ROC）曲线评价其对LN患者疾病活动度的预测价值。结果·LN患者血清sIL-2R和TNF-α水平显著高于对照组（均P<0.05）。LN患者血清sIL-2R水平与系统性红斑狼疮疾病活动指数（systemic lupus erythematosus disease activity index-2000，SLEDAI-2K）、24 h尿总蛋白（24 hours urine total protein，24h-UTP）、抗双链DNA抗体（anti-double stranded DNA antibody，anti-dsDNA）、血肌酐和高敏C反应蛋白（high sensitive C-reactive protein，h-CRP）呈正相关（均P<0.05），和补体C3呈负相关（P=0.002）。TNF-α水平与SLEDAI-2K、24h-UTP、血肌酐和h-CRP呈正相关（均P<0.05），但与anti-dsDNA和补体C3无明显相关性。LN活动组患者24h-UTP、肌酐、anti-dsDNA、TNF-α和sIL-2R水平显著高于非活动组（均P<0.05），补体C3水平低于非活动组（P=0.000）。sIL-2R（OR=1.011）和anti-dsDNA（OR=1.025）是提示LN患者疾病活动的预测因素（均P<0.05）。sIL-2R联合anti-dsDNA预测LN患者疾病活动度的曲线下面积为0.957（P=0.000）。结论·LN患者中血清sIL-2R和TNF-α水平升高，sIL-2R和TNF-α水平与LN疾病活动相关，sIL-2R联合anti-dsDNA可有效地预测LN患者疾病活动度。

关键词: 可溶性白介素2受体, 肿瘤坏死因子α, 狼疮性肾炎

Abstract:

Objective·To investigate the correlations of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-α (TNF-α) with lupus nephritis (LN) and their predictive values in disease activity of LN.

Methods·This was a cross-sectional study. From January 2018 to December 2018, 40 patients who underwent kidney biopsy and was diagnosed as having LN and 68 healthy controls in Renji Hospital, Shanghai Jiao Tong University School of Medicine were included. Clinical characteristics and laboratory parameters were collected and serum sIL-2R and TNF-α were measured. Serum sIL-2R and TNF-α were compared between the LN group and the control group. The correlations of sIL-2R and TNF-α with laboratory parameters of LN were evaluated by Spearman analysis. Further, the LN patients were divided into the active group and the non-active group. The predictive values of sIL-2R and TNF-α were evaluated by Logistic analysis and receiver operating characteristic (ROC) curve.

Results·Serum sIL-2R and TNF-α levels were significantly higher in the LN group than those in the control group (all P<0.05). Positive correlations were observed between sIL-2R and systemic lupus erythematosus disease activity index-2000 (SLEDAI-2K), 24 hours urine total protein (24h-UTP), anti-double stranded DNA antibody (anti-dsDNA), serum creatinine and high sensitive C-reactive protein (h-CRP) (all P<0.05), while a negative correlation was found between sIL-2R and C3 (P=0.002). Meanwhile, TNF-α positively correlated with SLEDAI-2K, 24h-UTP, serum creatinine and h-CRP, whereas no significant correlation was found between TNF-α and anti-dsDNA or C3. 24h-UTP, anti-dsDNA, serum creatinine, sIL-2R and TNF-α were significantly higher (all P<0.05) and C3 was lower in the active group than those in the non-active group of LN (P=0.000). Anti-dsDNA (OR=1.025) and sIL-2R (OR=1.011) were predictive factors of disease activity of LN (all P<0.05) and the area under ROC curve of their combination of prediction was 0.957 (P=0.000).

Conclusion·Serum sIL-2R and TNF-α levels increase in LN patients and are correlated with the disease activity of LN. Combining anti-dsDNA and sIL-2R can predict the disease activity of LN effectively.

Key words: soluble interleukin-2 receptor (sIL-2R), tumor necrosis factor-α (TNF-α), lupus nephritis (LN)

中图分类号:

R593.24⁺2

黄冠文, 包继文, 李子扬, 张敏芳, 周文彦, 王琴, 倪兆慧, 王玲. 可溶性白介素2受体和肿瘤坏死因子α对狼疮性肾炎活动度的预测价值[J]. 上海交通大学学报(医学版), 2021, 41(1): 55-61.

Guan-wen HUANG, Ji-wen BAO, Zi-yang LI, Min-fang ZHANG, Wen-yan ZHOU, Qin WANG, Zhao-hui NI, Ling WANG. Predictive value of soluble interleukin-2 receptor and tumor necrosis factor-α in disease activity of lupus nephritis[J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(1): 55-61.

Index	Control group (n=68)	LN group (n=40)	P value
Age/year	38.6±13.1	42.6±11.3	0.078
Sex/n (%)			0.057
Male	17 (25.0)	4 (10.0)
Female	51 (75.0)	36 (90.0)
WBC/(×10⁹·L^-1)	5.7±1.2	6.8±2.1	0.000
RBC/(×10¹²·L^-1)	4.4±0.6	4.1±0.8	0.017
Hemoglobin/(g·L^-1)	138.8±13.2	111.6±18.1	0.000
Platelet/(×10⁹·L^-1)	217.8±37.7	179.5±43.0	0.000
Albumin/(g·L^-1)	45.7±2.8	35.7±4.2	0.000
Serum creatinine/(μmol·L^-1)	57.9 (54.5, 62.2)	78.5 (67.6, 100.0)	0.000
h-CRP/(mg·L^-1)	0.3 (0.2, 0.4)	1.0 (0.3, 2.4)	0.048
24h-UTP/mg	-	1 580.0 (357.4, 7 214.0)	-
C3/(g·L^-1)	-	0.7±0.2	-
C4/(g·L^-1)	-	0.2±0.1	-
Anti-dsDNA	-	102.0 (39.1, 270.3)	-
ANA (+)/n (%)	-	30 (75.0)	-
Anti-Sm (+)/n (%)	-	23 (57.5)	-
Anti-SSA-Ro52 (+)/n (%)	-	17 (42.5)	-
Anti-SSA-Ro60 (+)/n (%)	-	19 (47.5)	-
ANuA (+)/n (%)	-	18 (45.0)	-
Anti-U1RNP (+)/n (%)	-	11 (27.5)	-

Index	Control group (n=68)	LN group (n=40)	P value
Age/year	38.6±13.1	42.6±11.3	0.078
Sex/n (%)			0.057
Male	17 (25.0)	4 (10.0)
Female	51 (75.0)	36 (90.0)
WBC/(×10⁹·L^-1)	5.7±1.2	6.8±2.1	0.000
RBC/(×10¹²·L^-1)	4.4±0.6	4.1±0.8	0.017
Hemoglobin/(g·L^-1)	138.8±13.2	111.6±18.1	0.000
Platelet/(×10⁹·L^-1)	217.8±37.7	179.5±43.0	0.000
Albumin/(g·L^-1)	45.7±2.8	35.7±4.2	0.000
Serum creatinine/(μmol·L^-1)	57.9 (54.5, 62.2)	78.5 (67.6, 100.0)	0.000
h-CRP/(mg·L^-1)	0.3 (0.2, 0.4)	1.0 (0.3, 2.4)	0.048
24h-UTP/mg	-	1 580.0 (357.4, 7 214.0)	-
C3/(g·L^-1)	-	0.7±0.2	-
C4/(g·L^-1)	-	0.2±0.1	-
Anti-dsDNA	-	102.0 (39.1, 270.3)	-
ANA (+)/n (%)	-	30 (75.0)	-
Anti-Sm (+)/n (%)	-	23 (57.5)	-
Anti-SSA-Ro52 (+)/n (%)	-	17 (42.5)	-
Anti-SSA-Ro60 (+)/n (%)	-	19 (47.5)	-
ANuA (+)/n (%)	-	18 (45.0)	-
Anti-U1RNP (+)/n (%)	-	11 (27.5)	-

Index	Non-active group (n=23)	Active group (n=17)	P value
Age/year	41.9±12.6	43.5±10.3	0.672
Sex/n (%)			0.574
Male	2 (8.7)	2 (11.8)
Female	21 (91.3)	15 (88.2)
Previous treatment/n (%)
Prednisone	23 (100.0)	15 (88.2)	0.174
Immunosuppressant	12 (52.2)	8 (47.1)	0.750
WBC/(×10⁹·L^-1)	7.3±2.6	6.4±1.5	0.185
RBC/(×10¹²·L^-1)	4.2±0.8	3.9±0.9	0.216
Hemoglobin/(g·L^-1)	115.3±18.6	106.7±16.1	0.147
Platelet/(×10⁹·L^-1)	183.0±42.7	174.7±43.1	0.558
Albumin/(g·L^-1)	37.0±4.2	34.8±4.0	0.108
Serum creatinine/(μmol·L^-1)	76.8±26.0	107.8±51.8	0.017
24h-UTP/mg	643.0 (289.0, 3 983.5)	3 856.6 (551.0, 8 839.0)	0.047
C3/(g·L^-1)	0.7±0.1	0.5±0.2	0.000
anti-dsDNA	52.1 (30.2, 140.0)	295.6 (125.8, 389.8)	0.000
h-CRP/(mg·L^-1)	0.3 (0.1, 1.3)	2.3 (0.1, 4.7)	0.501
Treg/%	11.5±3.5	10.1±3.7	0.434
TNF-α/(pg·mL^-1)	11.8±6.6	16.1±4.5	0.024
sIL-2R/(U·mL^-1)	455.2±141.1	687.8±190.0	0.000

Index	Non-active group (n=23)	Active group (n=17)	P value
Age/year	41.9±12.6	43.5±10.3	0.672
Sex/n (%)			0.574
Male	2 (8.7)	2 (11.8)
Female	21 (91.3)	15 (88.2)
Previous treatment/n (%)
Prednisone	23 (100.0)	15 (88.2)	0.174
Immunosuppressant	12 (52.2)	8 (47.1)	0.750
WBC/(×10⁹·L^-1)	7.3±2.6	6.4±1.5	0.185
RBC/(×10¹²·L^-1)	4.2±0.8	3.9±0.9	0.216
Hemoglobin/(g·L^-1)	115.3±18.6	106.7±16.1	0.147
Platelet/(×10⁹·L^-1)	183.0±42.7	174.7±43.1	0.558
Albumin/(g·L^-1)	37.0±4.2	34.8±4.0	0.108
Serum creatinine/(μmol·L^-1)	76.8±26.0	107.8±51.8	0.017
24h-UTP/mg	643.0 (289.0, 3 983.5)	3 856.6 (551.0, 8 839.0)	0.047
C3/(g·L^-1)	0.7±0.1	0.5±0.2	0.000
anti-dsDNA	52.1 (30.2, 140.0)	295.6 (125.8, 389.8)	0.000
h-CRP/(mg·L^-1)	0.3 (0.1, 1.3)	2.3 (0.1, 4.7)	0.501
Treg/%	11.5±3.5	10.1±3.7	0.434
TNF-α/(pg·mL^-1)	11.8±6.6	16.1±4.5	0.024
sIL-2R/(U·mL^-1)	455.2±141.1	687.8±190.0	0.000

Variable	Logistic regression coefficient B	Standard error	Wald	P value	OR (95%CI)
sIL-2R	0.011	0.005	5.156	0.023	1.011 (1.002?1.021)
Anti-dsDNA	0.025	0.009	7.594	0.006	1.025 (1.007?1.044)
Constant	-11.233	3.766	8.010	0.005	-

可溶性白介素2受体和肿瘤坏死因子α对狼疮性肾炎活动度的预测价值

Predictive value of soluble interleukin-2 receptor and tumor necrosis factor-α in disease activity of lupus nephritis

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