Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes
Densin and filtrin in the pancreas and in the kidney, targets for humoral autoimmunity in patients with type 1 diabetes
复制标题
DOI：
10.1002/dmrr.655
复制
发表时间：
2007-02-01
影响因子：
8
通讯作者：
Holthofer, Harry
中科院分区：
文献类型：
--
作者：
Rinta-Valkama, Johanna;Aaltonen, Petri;Holthofer, Harry
背景与目的胰岛细胞自身抗体的产生是I型糖尿病患者的一个典型现象。在胰腺中探索了最近显示存在于肾足细胞中的致密蛋白的表达。此外，我们研究了是否densin和filtrin，另一种分子之间共享的肾脏足细胞和胰岛细胞，可以作为自身抗原和是否对这些自身抗体可以检测到在1型diabetes.Methods胰腺densin的表达进行了研究，逆转录聚合酶链反应（RT-PCR）和免疫荧光。采用放射免疫沉淀法对66例儿童和青少年I型糖尿病患者及对照组进行了致密蛋白自身抗体（DAA）和滤过蛋白自身抗体（FAA）的检测。在诊断时和2年、5年和10年后获得血清样品。结果在胰腺中观察到Densin表达，定位于β细胞。在33%的患者中检测到DAA，并且通常在诊断时就已经看到阳性。FAA在11%的患者中观察到。随访期间，胰岛细胞抗体（伊卡）阳性、GADA阳性和蛋白酪氨酸磷酸酶相关胰岛抗原2抗体（IA-2A）阳性患者的比例下降，DAA也有类似趋势，但FAA没有。在14例有肾损伤体征的患者中，4例DAA阳性，2例FAA阳性。Densin和filtrin可以作为自身抗原，在1型糖尿病患者中可以检测到针对这些抗原的自身抗体。版权所有（c）2006约翰威利父子有限公司。
Background and aim The development of autoantibodies against antigens of the pancreatic islet cells is a typical phenomenon in patients with type I diabetes. The expression of densin, recently shown to be present in kidney podocytes, was explored in the pancreas. Additionally, we studied whether densin and filtrin, another molecule shared between the kidney podocytes and pancreatic islet cells, can act as autoantigens and whether autoantibodies against these can be detected in patients with type 1 diabetes.Methods Expression of pancreatic densin was studied with reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence. Children and adolescents (n = 66) with type I diabetes and control subjects were analysed for densin autoantibodies (DAA) and filtrin autoantibodies (FAA) using radioirnmunoprecipitation assay. The serum samples were obtained at the time of diagnosis and after a duration of 2, 5 and 10 years.Results Densin expression was observed in the pancreas, localising to the beta cells. DAA were detected in 33% of the patients and the positivity was typically seen already at diagnosis. FAA were observed in 11% of the patients. The proportion of islet cell antibody (ICA) positive, GADA positive and protein tyrosine phosphatase -related islet antigen 2 antibody (IA-2A)positive patients decreased during the follow-up period, and a similar trend was seen for DAA but not for FAA. Among the 14 patients with signs of renal injury, four tested positive for DAA and two for FAA.Conclusions Densin is a novel molecule shared by the kidney glomerular podocytes and pancreatic islet cells. Densin and filtrin can act as autoantigens, and autoantibodies against these can be detected in patients with type 1 diabetes. Copyright (c) 2006 John Wiley & Sons, Ltd.