Urine S100 proteins as potential biomarkers of lupus nephritis activity.
Urine S100 proteins as potential biomarkers of lupus nephritis activity.
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DOI：
10.1186/s13075-017-1444-4
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发表时间：
2017-10-24
影响因子：
4.9
通讯作者：
Brunner HI
中科院分区：
文献类型：
--
作者：
Turnier JL;Fall N;Thornton S;Witte D;Bennett MR;Appenzeller S;Klein-Gitelman MS;Grom AA;Brunner HI
需要改进的非侵入性生物标志物来准确检测狼疮性肾炎(LN)的活动性。本研究的目的是评价血清和尿液中的5种S100蛋白(S100A4、S100A6、S100A8/9和S100A12)在儿童期起病的系统性红斑狼疮(CSLE)中作为全球和肾脏系统特异性疾病活动的潜在生物标志物。在这项多中心研究中，使用商业酶联免疫吸附试验检测了四个CSLE队列和健康对照组的血清和尿液中的S100蛋白。根据生物样品的可用性，患者被分为四组：(1)纵向血清，(2)纵向尿液，(3)横断面血清，(4)横断面尿液。使用系统性红斑狼疮疾病活动指数2000(SLEDAI-2K)和SLEDAI-2K肾域评分来定义全球和肾脏疾病活动。统计分析采用非参数检验，包括Wilcoxon符号等级检验、Kruskal-Wallis检验、Mann-Whitney U检验和Spearman等级相关系数。活动期LN患者尿S100蛋白均高于活动期肾外疾病患者和健康对照组。随着LN的改善，所有患者的尿S100蛋白水平均下降，其中S100A4下降最为显著。增生期LN患者尿S100A4水平也高于膜性LN患者。肾脏S100A4染色定位于单核细胞、足细胞和远端肾小管上皮细胞。不管测试的是S100蛋白，血清水平并没有随着CSLE的改善而改变。CSLE患者尿S100水平升高与LN活性升高相关，而血清S100水平与疾病活动性无关。尿S100A4作为LN活动性生物标志物显示出最大的前景，因为随着LN的改善，尿中S100A4显著降低，尿液中孤立地升高，并且常驻肾细胞中染色阳性。本文的在线版本(doi：10.1186/s13075-017-1444-4)包含补充材料，授权用户可以使用。
Improved, noninvasive biomarkers are needed to accurately detect lupus nephritis (LN) activity. The purpose of this study was to evaluate five S100 proteins (S100A4, S100A6, S100A8/9, and S100A12) in both serum and urine as potential biomarkers of global and renal system-specific disease activity in childhood-onset systemic lupus erythematosus (cSLE). In this multicenter study, S100 proteins were measured in the serum and urine of four cSLE cohorts and healthy control subjects using commercial enzyme-linked immunosorbent assays. Patients were divided into cohorts on the basis of biospecimen availability: (1) longitudinal serum, (2) longitudinal urine, (3) cross-sectional serum, and (4) cross-sectional urine. Global and renal disease activity were defined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the SLEDAI-2K renal domain score. Nonparametric testing was used for statistical analysis, including the Wilcoxon signed-rank test, Kruskal-Wallis test, Mann-Whitney U test, and Spearman’s rank correlation coefficient. All urine S100 proteins were elevated in patients with active LN compared with patients with active extrarenal disease and healthy control subjects. All urine S100 protein levels decreased with LN improvement, with S100A4 demonstrating the most significant decrease. Urine S100A4 levels were also higher with proliferative LN than with membranous LN. S100A4 staining in the kidney localized to mononuclear cells, podocytes, and distal tubular epithelial cells. Regardless of the S100 protein tested, serum levels did not change with cSLE improvement. Higher urine S100 levels are associated with increased LN activity in cSLE, whereas serum S100 levels do not correlate with disease activity. Urine S100A4 shows the most promise as an LN activity biomarker, given its pronounced decrease with LN improvement, isolated elevation in urine, and positive staining in resident renal cells. The online version of this article (doi:10.1186/s13075-017-1444-4) contains supplementary material, which is available to authorized users.
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影响因子：
27.4
作者：
Holzinger, Dirk;Frosch, Michael;Wittkowski, Helmut
通讯作者：
Wittkowski, Helmut
影响因子：
2.6
作者：
Alvarado, A. S.;Malvar, A.;Rovin, B. H.
通讯作者：
Rovin, B. H.
影响因子：
3.9
作者：
Soyfoo, Muhammad S.;Roth, Johannes;Decaux, Guy
通讯作者：
Decaux, Guy
影响因子：
2.6
作者：
Perfumo, F;Martini, A
通讯作者：
Martini, A
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V