白介素-18在ANCA相关性小血管炎肾损害患者中的表达及其临床意义
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摘要
目的通过检测抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AASV)肾损害患者血清及尿液白介素-18(IL-18)水平,探讨IL-18在AASV肾损害应用中的可能价值。方法比较健康对照组与AASV组、AASV活动组与缓解组间血/尿IL-18水平,分析尿IL-18与传统病情活动性指标如ANCA滴度、血肌酐、C-反应蛋白(CRP)、伯明翰系统性血管炎活动度评分量表(BVAS)评分值等的相关性,绘制尿IL-18评估AASV活动性的ROC曲线,评价IL-18在AASV肾损害中的意义。结果AASV组尿IL-18水平比健康对照组显著升高(P<0.05),AASV活动组尿液与血液IL-18水平均高于缓解组(P<0.05)。治疗随访半年后,病情由活动转为缓解的患者尿IL-18水平较治疗前明显下降(P<0.05)。AASV患者尿IL-18与血清ANCA滴度、BVAS评分值呈正相关(P<0.05),与血肌酐、胱抑素C、CRP、尿微量白蛋白/肌酐比值、尿β_2-微球蛋白等无明显线性相关。AASV活动期患者的血、尿IL-18水平呈正相关(P<0.05)。尿IL-18评估AASV病情活动性的曲线下面积(AUC)为0.816(P<0.05),当检测的截点值为0.130 pg·mL~(-1)·Cr~(-1)时,其敏感度和特异度分别为85.7%和71.4%。结论AASV肾损害患者尿液IL-18水平升高,与疾病活动性相关,在早期预测AASV病情及活动性上有一定价值。
Objective To investigate the possible value of interleukin-18(IL-18) in the application of renal damage induced by ANCA associated small vessel vasculitis(AASV). Methods The levels of serum and urine IL-18 were compared between control group and AASV group,or between AASV active group and remission group. The correlation between urine IL-18 and other clinical indicators such as serum ANCA,creatinine,C-reactive protein(CRP) and BVAS score was analyzed. In combining with ROC curve of urine IL-18 in determining the activity of AASV,the significance of IL-18 in AASV renal damage was evaluated. Results The levels of urinary IL-18 in the AASV group were significantly higher than those in the control group(P < 0. 05),and the active AASV group had a higher expression of urine and serum IL-18 than the remission group(P <0. 05). Six months after treatment,urinary IL-18 levels in patients whose disease was changed from activity to remission were significantly decreased(P < 0. 05). Urinary IL-18 in AASV patients was positively correlated with serum ANCA and BVAS score(P < 0. 05),but had no significantly liner correlation with creatinine,serum cystatin C,C-reactive protein,urinary albumin/creatinine ratio and β_2-microglobulin. Serum and urine IL-1 8 had a positive correlation in AASV active group(P < 0. 05). The area under the ROC curve for urine IL-18 in diagnosis of renal damage in AASV w as 0. 8 1 6(P < 0. 0 5),w hen the cut-off value w as 0. 1 3 0 pg·m L~(-1)·Cr~(-1),the sensitivity and specificity w ere 8 5. 7 % and 7 1. 4 % respectively. Conclusions The levels of urinary IL-1 8 w ere elevated in patients w ith renal im pairm ent of AASV and correlated w ith disease activity. Urinary IL-1 8 had a certain value in the early prediction of AASV disease activity.
Objective To investigate the possible value of interleukin-18(IL-18) in the application of renal damage induced by ANCA associated small vessel vasculitis(AASV). Methods The levels of serum and urine IL-18 were compared between control group and AASV group,or between AASV active group and remission group. The correlation between urine IL-18 and other clinical indicators such as serum ANCA,creatinine,C-reactive protein(CRP) and BVAS score was analyzed. In combining with ROC curve of urine IL-18 in determining the activity of AASV,the significance of IL-18 in AASV renal damage was evaluated. Results The levels of urinary IL-18 in the AASV group were significantly higher than those in the control group(P < 0. 05),and the active AASV group had a higher expression of urine and serum IL-18 than the remission group(P <0. 05). Six months after treatment,urinary IL-18 levels in patients whose disease was changed from activity to remission were significantly decreased(P < 0. 05). Urinary IL-18 in AASV patients was positively correlated with serum ANCA and BVAS score(P < 0. 05),but had no significantly liner correlation with creatinine,serum cystatin C,C-reactive protein,urinary albumin/creatinine ratio and β_2-microglobulin. Serum and urine IL-1 8 had a positive correlation in AASV active group(P < 0. 05). The area under the ROC curve for urine IL-18 in diagnosis of renal damage in AASV w as 0. 8 1 6(P < 0. 0 5),w hen the cut-off value w as 0. 1 3 0 pg·m L~(-1)·Cr~(-1),the sensitivity and specificity w ere 8 5. 7 % and 7 1. 4 % respectively. Conclusions The levels of urinary IL-1 8 w ere elevated in patients w ith renal im pairm ent of AASV and correlated w ith disease activity. Urinary IL-1 8 had a certain value in the early prediction of AASV disease activity.
引文
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[16]Han WK,Choi HK,Roth RM,et al.Serial ANCA titers:useful tool for prevention of relapses in ANCA-associated vasculitis[J].Kidney Int,2003,63(3):1079-1085.
[17]Luqmani RA,Bacon PA,Moots RJ,et al.Birmingham vasculitis activity score(BVAS)in systemic necrotizing vasculitis[J].QJM,1994,87(11):671-678.
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[19]Wawrocki S,Druszczynska M,Kowalewicz-Kulbat M,et al.Interleukin 18(IL-18)as a target for immune intervention[J].Acta Biochimica Polonica,2016,63(1):59-63.
[20]Parikh CR,Abraham E,Ancukiewicz M,et al.Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit[J].J Am Soc Nephrol,2005,16(10):3046-3052.
[21]Pressler BM,Falk RJ,Preston CA.Interleukin-18,neutrophils,and ANCA[J].Kidney Int,2006,69(3):424-425.
[22]Hewins P,Morgan MD,Holden N,et al.IL-18 is upregulated in the kidney and primes neutrophil responsiveness in ANCA-associated vasculitis[J].Kidney Int,2006,69(3):605-615.
[23]Novick D,Elbirt D,Dinarello CA,et al.Interleukin-18 binding protein in the sera of patients with wegener’s granulomatosis[J].J Clin Immunol,2009,29(1):38-45.
[24]蔡娟,王卫黎,黄鑫,等.抗中性粒细胞胞浆抗体相关性血管炎患者白细胞介素18的水平及意义[J].临床肾脏病杂志,2015,15(9):530-534.
[2]Lyons PA,Rayner TF,Trivedi S,et al.Genetically distinct subsets within ANCA-associated vasculitis[J].N Engl J Med,2012,367(3):214-223.
[3]陈凌舟,彭卫华.抗中性粒细胞胞质抗体相关性小血管炎发病机制研究进展[J].临床肾脏病杂志,2017,17(3):185-188.
[4]Morgan MD,Harper L,Williams J,et al.Anti-neutrophil cytoplasm-associated glomerulonephritis[J].J Am Soc Nephrol,2006,17(5):1224-1234.
[5]赵明辉,章友康,刘玉春,等.抗中性粒细胞胞浆抗体相关小血管炎的系统表现[J].中华内科杂志,2000,39(1):50.
[6]彭卫华,陈凌舟,许敏敏,等.ANCA相关性小血管炎肾损害患者尿液肾损伤生物标志物的检测及意义[J].中国中西医结合肾病杂志,2017,18(10):867-872.
[7]Jafari-Nakhjavani MR,Abedi-Azar S,Nejati B.Correlation of plasma interleukin-18 concentration and severity of renal involvement and disease activity in systemic lupus erythematosus[J].JNephropathol,2016,5(1):28-33.
[8]Elneam AI,Mansour NM,Zaki NA,et al.Serum interleukin-18and its gene haplotypes profile as predictors in patients with diabetic nephropathy[J].Open Access Maced J Med Sci,2016,4(3):324-328.
[9]Liang D,Ma W,Yao C,et al.Imbalance of interleukin 18 and interleukin 18 binding protein in patients with lupus nephritis[J].Cell Mol Immunol,2006,3(4):303-306.
[10]Andreucci M,Faga T,Riccio E,et al.The potential use of biomarkers in predicting contrast-induced acute kidney injury[J].Int J Nephrol Renovasc Dis,2016,9:205-221.
[11]Jennette JC,Falk RJ,Bacon PA,et al.2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides[J].Arthritis Rheum,2013,65(1):1-11.
[12]胡伟新,黎磊石.中国肾脏病学[M].北京:人民军医出版社,2008:523-554.
[13]Mukhtyar C,Lee R,Brown D,et al.Modification and validation of the birmingham vasculitis activity score(Version 3)[J].Ann Rheum Dis,2009,68(12):1827-1832.
[14]王海燕.KDIGO肾小球肾炎临床实践指南[M].北京:人民卫生出版社,2013:269-292.
[15]陈凌舟,许敏敏,彭卫华.ANCA相关性血管炎的诊治和疗效评估指标研究近况[J].中国中西医结合肾病杂志,2017,18(2):173-176.
[16]Han WK,Choi HK,Roth RM,et al.Serial ANCA titers:useful tool for prevention of relapses in ANCA-associated vasculitis[J].Kidney Int,2003,63(3):1079-1085.
[17]Luqmani RA,Bacon PA,Moots RJ,et al.Birmingham vasculitis activity score(BVAS)in systemic necrotizing vasculitis[J].QJM,1994,87(11):671-678.
[18]Kawai H,Banno S,Kikuchi S,et al.Retrospective analysis of factors predicting end-stage renal failure or death in patients with microscopic polyangiitis with mainly renal involvement[J].Clin Exp Nephrol,2014,18(5):795-802.
[19]Wawrocki S,Druszczynska M,Kowalewicz-Kulbat M,et al.Interleukin 18(IL-18)as a target for immune intervention[J].Acta Biochimica Polonica,2016,63(1):59-63.
[20]Parikh CR,Abraham E,Ancukiewicz M,et al.Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit[J].J Am Soc Nephrol,2005,16(10):3046-3052.
[21]Pressler BM,Falk RJ,Preston CA.Interleukin-18,neutrophils,and ANCA[J].Kidney Int,2006,69(3):424-425.
[22]Hewins P,Morgan MD,Holden N,et al.IL-18 is upregulated in the kidney and primes neutrophil responsiveness in ANCA-associated vasculitis[J].Kidney Int,2006,69(3):605-615.
[23]Novick D,Elbirt D,Dinarello CA,et al.Interleukin-18 binding protein in the sera of patients with wegener’s granulomatosis[J].J Clin Immunol,2009,29(1):38-45.
[24]蔡娟,王卫黎,黄鑫,等.抗中性粒细胞胞浆抗体相关性血管炎患者白细胞介素18的水平及意义[J].临床肾脏病杂志,2015,15(9):530-534.