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
Abstract
BACKGROUND

In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice.

AIM

To investigate the frequency of anti-islet autoantibodies in AITD patients.

METHODS

Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups.

RESULTS

The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, 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 AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, 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). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves’ disease and Hashimoto’s thyroiditis in any of the groups.

CONCLUSION

Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

Keywords: Anti-islet autoantibodies; Autoimmune thyroid disease; Real-world practice; Retrospective study; Type 1 diabetes

Core Tip: This study presents the clinical utility of 3 Screen Islet Cell Autoantibody enzyme-linked immunosorbent assay (3 Screen ICA ELISA) in identifying anti-islet autoantibody-positive individuals among patients with autoimmune thyroid disease (AITD). Our findings demonstrate that 5.1% of AITD patients test positive for 3 Screen ICA with titers comparable to those of patients with type 1 diabetes (T1D) despite not having diabetes themselves. These results have the potential to enhance the staging and early diagnosis of T1D in AITD patients in clinical practice.