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Review
. 2023 Jun 11;24(12):10012.
doi: 10.3390/ijms241210012.

Anti-Islet Autoantibodies in Type 1 Diabetes

Eiji Kawasaki  1
Affiliations
Review

Anti-Islet Autoantibodies in Type 1 Diabetes

Eiji Kawasaki. Int J Mol Sci. .

Abstract

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. A combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate a more accurate diagnosis and prediction of autoimmune disorders. The aim of this review is to summarize what is known about the clinical significance of anti-islet autoantibodies in the pathogenesis and diagnosis of T1D.

Keywords: enzyme-linked immunosorbent assay; epitope; glutamic acid decarboxylase; latent-autoimmune diabetes in adults; prediction; type 1 diabetes.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Chronology of anti-islet autoantibody discovery. Anti-islet autoantibodies used for prediction and diagnoses of T1D are IAA, GADA, IA-2A, and ZnT8A.
Figure 2
Figure 2
Three stages of natural history of T1D.
Figure 3
Figure 3
Combinatorial analysis of anti-islet autoantibodies in patients with acute-onset T1D (A), SPIDDM (B), and fulminant T1D (C) Adapted with permission from Ref. [35].
Figure 3
Figure 3
Combinatorial analysis of anti-islet autoantibodies in patients with acute-onset T1D (A), SPIDDM (B), and fulminant T1D (C) Adapted with permission from Ref. [35].
Figure 4
Figure 4
Illustration of antigenic epitopes recognized by T1D sera in GAD65 (A), IA-2 (B), and ZnT8 (C) proteins.
Figure 4
Figure 4
Illustration of antigenic epitopes recognized by T1D sera in GAD65 (A), IA-2 (B), and ZnT8 (C) proteins.
Figure 5
Figure 5
Prevalence of GADA, IA-2A, ZnT8A, and IAA in 788 insulin-naïve adult-onset patients with diabetes.
Figure 6
Figure 6
Comparison of GADA epitopes (top) and IgG subclasses (bottom) in T1D patients without and with autoimmune thyroid disease. (Left panel) T1D without AITD. (Right panel) T1D with AITD.
Figure 7
Figure 7
Clinical utilities of anti-islet autoantibodies in patients with diabetes.
See this image and copyright information in PMC

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