Ahlgren Kerstin M, Fall Tove, Landegren Nils, Grimelius Lars, von Euler Henrik, Sundberg Katarina, Lindblad-Toh Kerstin, Lobell Anna, Hedhammar Åke, Andersson Göran, Hansson-Hamlin Helene, Lernmark Åke, Kämpe Olle
Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
PLoS One. 2014 Aug 25;9(8):e105473. doi: 10.1371/journal.pone.0105473. eCollection 2014.
AIMS/HYPOTHESIS: Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.
Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.
None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.
CONCLUSIONS/INTERPRETATIONS: Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
目的/假设:糖尿病是犬类最常见的内分泌疾病之一,通常认为其起源于自身免疫。尽管人类1型糖尿病(T1D)和犬糖尿病的临床表现相似,但其病因可能不同。本研究的目的是调查类似于人类T1D的自身免疫病因在犬类中是否如先前报道的那样普遍。
对来自40个不同品种的121只糖尿病犬的血清进行胰岛细胞抗体(ICA)和GAD65自身抗体(GADA)检测,并与133只健康犬的血清进行比较。使用犬类和人类冰冻切片通过间接免疫荧光检测ICA。通过对人类和犬类GAD65进行体外转录和翻译(ITT),然后进行免疫沉淀来检测GADA。对5只糖尿病犬和2只对照犬的胰腺切片进行组织病理学检查,包括胰岛素、胰高血糖素、生长抑素和胰多肽的免疫染色。
在犬类或人类冰冻胰岛切片上,所分析的犬血清中没有一个ICA检测呈阳性。然而,一只糖尿病犬的血清在犬类GADA检测中呈弱阳性,一只健康犬的血清在人类GADA检测中呈弱阳性。组织病理学显示内分泌胰岛有明显的退行性变化,包括空泡化和胰岛素免疫染色的不同程度丧失。未发现炎症迹象。
结论/解读:与先前的观察结果相反,基于使用四种不同检测方法对胰岛蛋白的体液自身反应性测试结果以及组织病理学检查,我们没有发现任何证据支持犬糖尿病存在胰岛自身免疫病因。