Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Anti-Islet Autoantibodies in Type 1 Diabetes

Version 1 : Received: 3 May 2023 / Approved: 4 May 2023 / Online: 4 May 2023 (05:18:16 CEST)

A peer-reviewed article of this Preprint also exists.

Kawasaki, E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int. J. Mol. Sci. 2023, 24, 10012. Kawasaki, E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int. J. Mol. Sci. 2023, 24, 10012.

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. 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 more accurate diagnosis and prediction of autoimmune disorders.

Keywords

Enzyme-linked immunosorbent assay; Epitope, Glutamic acid decarboxylase; Latent-autoimmune diabetes in adults; Prediction; Type 1 diabetes

Subject

Medicine and Pharmacology, Endocrinology and Metabolism

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