electrochemiluminescence-assays-for-human-islet-autoantibodies

Electrochemiluminescence Assays for Human Islet Autoantibodies

Pinpointing islet autoantibodies associated with type 1 diabetes (T1D) leads the way to project and deter this disease in the general population. A novel ...

a-high-throughput-electrochemiluminescence-7-plex-assay

A High-Throughput Electrochemiluminescence 7-Plex Assay Simultaneously Screening for Type 1 Diabetes and Multiple Autoimmune Diseases

Islet autoantibodies (IAbs) are widely used in type 1 diabetes (T1D) diagnosis and prediction. Four major IAbs to insulin (IAA), glutamate ...

University of Colorado Denver

First Affiliated Hospital of Nanjing Medical University

University of Colorado School of Medicine

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobinA1c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1DM patients (duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

Islet Autoantibody Detection by Electrochemiluminescence (ECL) Assay.

Islet autoantibodies (IAbs) are the most reliable biomarkers to assess risk of progression to clinical type 1 diabetes (T1D). There are four major biochemically defined IAbs currently used in clinical trials that are equally important for disease prediction. The current screening methods use a radio-binding assay (RBA) for single IAb measurement, which are laborious and inefficient for large-scale screening. More importantly, up to 40% of patients with T1D have other autoimmune conditions that can be identified through relevant autoantibody testing. Thus, there is a need to screen for T1D and other autoimmune diseases simultaneously.

High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously.

Type 1 diabetes (T1D) is now predictable by measuring specific islet autoantibodies (IAbs). Almost all children who developed multiple IAbs will progress to T1D with time, while individuals with single IAb have a very low risk although it is an important earlier biomarker. The poor prediction of single IAb has been found to be associated with IAb affinity. Majority of single IAb generated in current standard IAb radio-binding assay (RBA) are of low affinity, which have been demonstrated low risk in T1D development. New generation of nonradioactive IAb assay with electrochemiluminescence (ECL) technology has been shown to discriminate high-affinity from low-affinity IAbs and greatly improve sensitivity and disease specificity. With a high-affinity IAb assay, like ECL assay, single IAb will be expected to be a reliable biomarker for T1D early prediction. Although appearance of IAbs is most reliable biomarkers for T1D, there are no direct evidences that IAbs contribute to β-cell damage. With recent studies on ZnT8, a merging protein on β-cell surface membrane associated with insulin secretion, a subclass of ZnT8 autoantibodies directed to extra-cellular epitopes of ZnT8 on β-cell surface has recently been identified in T1D patients and these cell surface autoantibodies have been found to appear very early, before other IAbs. These findings lead us to a hypothesis that the immunogenic epitopes on β-cell surface might be early targets for autoimmune disease and IAbs to cell surface epitopes might be involved in β-cell destruction, which will change the paradigm of IAbs in T1D pathogenesis.

ArticleTotal : 2	Year
Publication title	2018
Publication title	2020

Article	Year
The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients. Science China. Life sciences\| PubMed ID: 27225179	2016
Islet Autoantibody Detection by Electrochemiluminescence (ECL) Assay. Journal of clinical & cellular immunology\| PubMed ID: 29487479	2017
High-throughput multiplexed autoantibody detection to screen type 1 diabetes and multiple autoimmune diseases simultaneously. EBioMedicine\| PubMed ID: 31447394	2019
Islet autoantibodies in disease prediction and pathogenesis. Diabetology international\| PubMed ID: 31949998	2020

Yong Gu

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