**Table 1.**

*Autoantibodies to pancreatic antigens, prevalence rate, and risk of developing T1D in 5 years.*

There are five commonly tested AAb markers used in the diagnosis of T1D, which include ICA (islet-cell cytoplasmic AAb), GADA (glutamic acid decarboxylase (GAD) AAb), IA-2A (insulinoma 2 (IA-2)-associated AAb), IAA (insulin AAb), and ZNT8A (zinc transporter 8 AAb) (**Table 1**). At least one of the five autoantibodies is present in >95% of individuals with T1D upon hyperglycemia detection [8]. Patients with multiple autoantibody positivity are at a higher risk of developing T1D, although this risk varies depending on age, antibody type, and metabolic status [12]. However, a subset of patients who do not have any of the above AAbs at diagnosis have been found, indicating either a possibility of insensitive tests or the presence of additional T1D-associated autoantibodies in these patients.

Although AAbs appear before T1D diagnosis, they appear relatively late in the autoimmune process. T1D prevention may be more effective before the onset of the active autoimmune response and appearance of AAbs, suggesting that AAbs may not be effective markers to identify high-risk groups for T1D prevention [2]. Overall, AAbs are not useful as biomarkers for therapeutic outcomes and do not track disease progression [13]. Thus, it is crucial to investigate additional biomarkers that can serve as predictors of disease progression.

Autoreactive CD4+ and CD8+ T cells are thought to be the main mediators behind beta cell destruction in T1D [6, 14]. Insulitis, or leukocyte invasion of pancreatic islets, has been observed in mouse models and pancreatic biopsies of T1D patients, with infiltrates, predominately consisting of CD8+ cytotoxic T cells [15]. As autoreactive T cells play a direct role in beta cell destruction, T cell markers have the potential to provide unique insights into the pathogenesis and progression of T1D [6]. Despite their large potential, T cell biomarkers run into many challenges, making them difficult to use routinely. T cell quantification assays are limited by their lack of sensitivity [15, 16], as well as the low frequency of autoreactive T cells in peripheral blood and low avidity for peptide MHC ligands [17]. Avidity for TCR is hoped to increase through engineering the MHC peptide ligand into a multimer in recent studies [18]. Other advancements are being made in T cell biomarker identification, but further validation and standardization of the most promising biomarkers and assays are needed before widespread use [19, 20].
