Observational Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. May 15, 2024; 15(5): 935-944
Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.935
Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease
Eiji Kawasaki, Hidekazu Tamai, Takahiro Fukuyama, Yoko Sagara, Ryutaro Hidaka, Aira Uchida, Masayuki Tojikubo, Narihito Tatsumoto, Yuko Akehi, Yuji Hiromatsu
Eiji Kawasaki, Hidekazu Tamai, Takahiro Fukuyama, Yoko Sagara, Ryutaro Hidaka, Aira Uchida, Masayuki Tojikubo, Narihito Tatsumoto, Yuko Akehi, Yuji Hiromatsu, The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, Kurume 830-8577, Japan
Author contributions: Kawasaki E designed and performed the research and wrote the manuscript; Kawasaki E contributed to the conception, design, analysis, and interpretation of data for the work. Tamai H, Fukuyama T, Sagara Y, Hidaka R, Uchida A, Tojikubo M, Akehi Y, and Hiromatsu Y contributed to interpreting data for the work. All authors have read and approved the final manuscript.
Institutional review board statement: This study’s protocol has been reviewed and approved by the ethics committee of Shin-Koga Hospital.
Informed consent statement: Informed consent was obtained in the form of opt-out on the website, and all patients were allowed to refuse participation according to the Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects and the local Institutional Review Board Approval due to the use of existing samples that have undergone clinical testing (residual samples).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Eiji Kawasaki, MD, PhD, Director, The Diabetes, Thyroid and Endocrine Center, Shin-Koga Hospital, 120 Tenjin-cho, Kurume 830-8577, Japan. e-kawasaki@tenjinkai.or.jp
Received: January 27, 2024
Peer-review started: January 27, 2024
First decision: February 5, 2024
Revised: February 7, 2024
Accepted: March 11, 2024
Article in press: March 11, 2024
Published online: May 15, 2024
Processing time: 104 Days and 10.4 Hours
ARTICLE HIGHLIGHTS
Research background

Anti-islet autoantibodies serve as valuable markers for predicting and diagnosing type 1 diabetes (T1D). It is well-established that 20%-30% of T1D patients also have autoimmune thyroid disease (AITD). However, data regarding anti-islet autoantibodies in AITD patients remain limited. The 3 Screen Islet Cell Autoantibody enzyme-linked immunosorbent assay (3 Screen ICA ELISA) is a multiplex anti-islet autoantibody assay capable of simultaneously measuring autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A).

Research motivation

The motivation behind this research is to investigate the frequency and titer of anti-islet autoantibodies in patients with AITD, aiming to facilitate the staging and early diagnosis of T1D.

Research objectives

The primary objectives of this research are as follows: (1) To determine the frequency and titer of anti-islet autoantibodies in AITD patients using the 3 Screen ICA ELISA method; and (2) To compare these findings to those of individual autoantibodies, particularly GADA, which are commonly the first markers assessed in general clinical practice.

Research methods

The research methodology involved the following steps: (1) Selection of a cohort of 495 patients with AITD, categorized into three groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396); and (2) Examination of the frequency of anti-islet autoantibodies, including 3 Screen ICA, GADA, IA-2A, and ZnT8A using the bridging-type ELISA method.

Research results

The key findings of the study include: (1) Frequencies of 3 Screen ICA in AITD patients with T1D, AITD patients with T2D, and those without diabetes being 88.9%, 6.2%, and 5.1%, with no significant difference between the latter two groups; (2) The frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in those without diabetes compared to GADA, respectively, and a significant proportion of 3 Screen ICA-positive patients were negative for GADA (12.5%, 20.0%, and 20.0%); and (3) There was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index).

Research conclusions

This study concludes that some AITD patients without diabetes exhibit comparable 3 Screen ICA titers to those observed in AITD patients with T1D. These findings suggest that 3 Screen ICA is outperforms GADA in identifying latent anti-islet autoantibody-positive individuals within the AITD patient population.

Research perspectives

To further investigate the predictive potential of 3 Screen ICA for the development of T1D, it is recommended that prospective studies be conducted in the future. These studies should focus on tracking changes in glucose tolerance and endogenous insulin secretion in AITD patients with T2D and those without diabetes. Such investigations will provide valuable insights into the clinical utility of 3 Screen ICA in identifying individuals at risk of transitioning to T1D.