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<p>A proportion of patients with new-onset diabetes share similar symptoms with type 1 diabetes (T1D) patients but they are negative for islet antigen-specific autoantibodies. This study was to develop an islet antigen-specific CD8<sup>+</sup> T-cell assay to provide autoimmune evidence regarding these “suspected” T1D patients. HLA-A*0201 individuals with autoAbs<sup>+</sup> T1D, autoAbs<sup>−</sup> suspected T1D, and type 2 diabetes, along with HLA-A*0201 healthy controls were recruited. Using interferon-γ enzyme-linked immunospot assays, the percentages of participants in each group with various islet antigen-specific CD8<sup>+</sup> T cells were determined. Sixteen out of the 28 islet antigen-specific epitopes tested were T1D specific, meaning that there was a significantly (<i>P</i> &lt; 0.05) greater epitope positivity rate in the autoAbs<sup>+</sup> T1D cohort than in the healthy controls. Using a cutoff value of two positive epitopes, the 16-epitope panel led to a sensitivity of 75.0% and a specificity of 94.4% regarding the autoAbs<sup>+</sup> T1D patients. Even when using an optimized five-epitope panel, the results were highly accurate. Notably, in the application phase of the study, 77.8% of a new cohort of autoAbs<sup>−</sup> suspected T1D patients exhibited positivity when using the five-epitope optimized panel. This highly accurate method, especially for pediatric patients, will improve clinical diagnosis and etiological classification of autoimmune T1D.</p> Graphic Abstract <p></p>

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Pivotal epitopes for islet antigen-specific CD8+ T cell detection improve classification of suspected type 1 diabetes with the HLA-A*0201 allele

  • 期刊论文

  • 发表日期：

    2025年3月26日

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  • Yang Chen,
  • Min Shen,
  • Yong Gu,
  • Xinyu Xu,
  • Lingling Bian,
  • Fan Yang,
  • Shuang Chen,
  • Li Ji,
  • Jin Liu,
  • Jing Zhu,
  • Zheng Zhang,
  • Qi Fu,
  • Yun Cai,
  • Heng Chen,
  • Kuanfeng Xu,
  • Min Sun,
  • Xuqin Zheng,
  • Jie Shen,
  • Hongwen Zhou,
  • Mei Zhang,
  • Kathryn Haskins,
  • Liping Yu,
  • Tao Yang,
  • Yun Shi

摘要

A proportion of patients with new-onset diabetes share similar symptoms with type 1 diabetes (T1D) patients but they are negative for islet antigen-specific autoantibodies. This study was to develop an islet antigen-specific CD8+ T-cell assay to provide autoimmune evidence regarding these “suspected” T1D patients. HLA-A*0201 individuals with autoAbs+ T1D, autoAbs− suspected T1D, and type 2 diabetes, along with HLA-A*0201 healthy controls were recruited. Using interferon-γ enzyme-linked immunospot assays, the percentages of participants in each group with various islet antigen-specific CD8+ T cells were determined. Sixteen out of the 28 islet antigen-specific epitopes tested were T1D specific, meaning that there was a significantly (P < 0.05) greater epitope positivity rate in the autoAbs+ T1D cohort than in the healthy controls. Using a cutoff value of two positive epitopes, the 16-epitope panel led to a sensitivity of 75.0% and a specificity of 94.4% regarding the autoAbs+ T1D patients. Even when using an optimized five-epitope panel, the results were highly accurate. Notably, in the application phase of the study, 77.8% of a new cohort of autoAbs− suspected T1D patients exhibited positivity when using the five-epitope optimized panel. This highly accurate method, especially for pediatric patients, will improve clinical diagnosis and etiological classification of autoimmune T1D.

Graphic Abstract