活化白细胞黏附分子（ALCAM）：2型糖尿病合并糖尿病肾病患者的一种新型生物标志物。
ALCAM a novel biomarker in patients with type 2 diabetes mellitus complicated with diabetic nephropathy.
作者信息
Sulaj Alba, Kopf Stefan, Gröne Elisabeth, Gröne Hermann-Josef, Hoffmann Sigrid, Schleicher Erwin, Häring Hans-Ulrich, Schwenger Vedat, Herzig Stephan, Fleming Thomas, Nawroth Peter P, von Bauer Rüdiger
机构信息
Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
Department of Medicine I and Clinical Chemistry, University of Heidelberg, INF 410, 69120 Heidelberg, Germany.
出版信息
J Diabetes Complications. 2017 Jun;31(6):1058-1065. doi: 10.1016/j.jdiacomp.2017.01.002. Epub 2017 Jan 21.
BACKGROUND & AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN.
METHODS
A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA. Expression of ALCAM and S100B in kidney histology from patients with DN was determined by immunohistochemistry. Cell expression of ALCAM and S100B was analyzed through confocal immunofluorescence microscopy.
RESULTS
Serum concentration of sALCAM was increased in diabetic patients with DN compared to non-diabetic (59.85±14.99ng/ml vs. 126.88±66.45ng/ml, P<0.0001). Moreover sALCAM correlated positively with HbA1c (R=0.31, P<0.0001), as well as with the stages of chronic kidney disease and negatively correlated with eGFR (R=-0.20, P<0.05). In diabetic patients with normal albuminuria sALCAM was increased compared to patients with DN (126.88±66.45ng/ml vs. 197.50±37.17ng/ml, P<0.0001). In diabetic patients, ALCAM expression was significantly upregulated in both the glomeruli and tubules (P<0.001). ALCAM expression in the glomeruli correlated with presence of sclerosis (R=0.25, P<0.001) and localized mainly in the podocytes supporting the hypothesis that membrane bound ALCAM drives diabetic nephropathy and thus explaining sALCAM decrease in diabetic patients with DN. The expression of S100B was increased significantly in the glomeruli of diabetic patients (P<0.001), but not in the tubules. S100B was as well localized in the podocytes.
CONCLUSIONS
This study identifies for the first time ALCAM as a potential mediator in the late complications of diabetes in the kidney.
背景与目的
活化白细胞细胞黏附分子（ALCAM/CD166）的功能类似于晚期糖基化终产物受体，后者与糖尿病肾病（DN）的发生发展有关。我们研究了DN患者中ALCAM及其配体S100B的表达情况。
方法
通过酶联免疫吸附测定（ELISA）评估了34例非糖尿病患者、29例2型糖尿病且蛋白尿正常的患者以及107例2型糖尿病合并DN的患者血清中可溶性ALCAM（sALCAM）的浓度。采用免疫组织化学法测定DN患者肾脏组织中ALCAM和S100B的表达。通过共聚焦免疫荧光显微镜分析ALCAM和S100B的细胞表达情况。
结果
与非糖尿病患者相比，DN糖尿病患者的血清sALCAM浓度升高（59.85±14.99ng/ml对126.88±66.45ng/ml，P<0.0001）。此外，sALCAM与糖化血红蛋白（HbA1c）呈正相关（R=0.31，P<0.0001），也与慢性肾脏病分期呈正相关，与估算肾小球滤过率（eGFR）呈负相关（R=-0.20，P<0.05）。与DN患者相比，2型糖尿病且蛋白尿正常的患者sALCAM升高（126.88±66.45ng/ml对197.50±37.17ng/ml，P<0.0001）。在糖尿病患者中，肾小球和肾小管中的ALCAM表达均显著上调（P<0.001）。肾小球中ALCAM的表达与硬化的存在相关（R=0.25，P<0.001），且主要定位于足细胞，这支持了膜结合ALCAM驱动糖尿病肾病的假说，从而解释了DN糖尿病患者sALCAM降低的原因。糖尿病患者肾小球中S100B的表达显著增加（P<0.001），但肾小管中未增加。S100B也定位于足细胞。
结论
本研究首次确定ALCAM是糖尿病肾脏晚期并发症的潜在介质。
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