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1型糖尿病自身免疫不同阶段儿童对小麦多肽刺激的CD4⁺ T细胞增殖反应。

CD4⁺ T-cell proliferation responses to wheat polypeptide stimulation in children at different stages of type 1 diabetes autoimmunity.

作者信息

Hamari Susanna, Kirveskoski Tiina, Glumoff Virpi, Kulmala Petri, Simell Olli, Knip Mikael, Ilonen Jorma, Veijola Riitta

机构信息

Department of Pediatrics, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland; Department of Medical Microbiology and Immunology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.

出版信息

Pediatr Diabetes. 2015 May;16(3):177-88. doi: 10.1111/pedi.12256. Epub 2015 Jan 30.

Abstract

AIMS

Our aim was to study whether immune responses to wheat-based proteins are related to the development of type 1 diabetes.

METHODS

We analysed proliferative T-cell responses after in vitro gliadin, gluten, whole wheat, and tetanus toxoid stimulation with a carboxyfluorescein succinimidyl ester (CFSE) based T-cell proliferation assay in children at various phases of type 1 diabetes autoimmunity and in healthy autoantibody-negative control children.

RESULTS

At an early stage of beta cell autoimmunity the strength and frequencies of positive proliferation responses to gliadin, gluten, and whole wheat did not differ between newly seroconverted children positive for one islet autoantibody and the controls. However, in prediabetic children with at least two islet autoantibodies and also in children with newly diagnosed type 1 diabetes positive T-cell responses to gliadin were significantly less frequent and the strength of gliadin responses was reduced when compared to the controls. No differences were seen in T-cell responses to wheat-based antigens when comparing children with long-lasting type 1 diabetes with healthy controls.

CONCLUSIONS/INTERPRETATION: Decreased in vitro T-cell responses to wheat-based antigens were observed in children with multiple islet autoantibodies and in those with newly diagnosed type 1 diabetes, probably reflecting a generally aberrant immune response during the development of type 1 diabetes.

摘要

目的

我们的目的是研究对小麦蛋白的免疫反应是否与1型糖尿病的发生有关。

方法

我们使用基于羧基荧光素琥珀酰亚胺酯(CFSE)的T细胞增殖试验,分析了1型糖尿病自身免疫不同阶段的儿童以及健康的自身抗体阴性对照儿童在体外接受麦醇溶蛋白、麸质、全麦和破伤风类毒素刺激后的T细胞增殖反应。

结果

在β细胞自身免疫的早期阶段,新出现一种胰岛自身抗体血清转化阳性的儿童与对照组相比,对麦醇溶蛋白、麸质和全麦的阳性增殖反应强度和频率没有差异。然而,与对照组相比,至少有两种胰岛自身抗体的糖尿病前期儿童以及新诊断为1型糖尿病的儿童对麦醇溶蛋白的阳性T细胞反应频率显著降低,且麦醇溶蛋白反应强度减弱。将患有长期1型糖尿病的儿童与健康对照组进行比较时,未发现对基于小麦的抗原的T细胞反应存在差异。

结论/解读:在患有多种胰岛自身抗体的儿童和新诊断为1型糖尿病的儿童中,观察到体外对基于小麦的抗原的T细胞反应降低,这可能反映了1型糖尿病发展过程中普遍存在的异常免疫反应。

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