Aims: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID-19). Pre-existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS-CoV-2 antigens in unexposed patients with T1D. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were collected from SARS-CoV-2 unexposed patients with T1D and healthy control subjects. SARS-CoV-2 specific T cells were identified in PBMCs by ex-vivo interferon (IFN)γ-ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. Results: T1D patients unexposed to SARS-CoV-2 exhibited higher rates of virus-specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT-8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT-8 autoantigens. Conclusions: The increased frequency of SAR-CoV-2- reactive T cells in T1D patients might protect against severe COVID-19 and overt infections. These results emphasise the long-standing association between viral infections and T1D.

T-cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes

Palmieri, Camillo;Santamaria, Gianluca;Cristiani, Costanza Maria;Garofalo, Cinzia;Abatino, Antonio;Parise, Martina;Aversa, Ilenia;Malanga, Donatella;Gallo, Raffaella;Cuda, Giovanni;Viglietto, Giuseppe;Costanzo, Francesco;Gnasso, Agostino;Irace, Concetta
2024-01-01

Abstract

Aims: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID-19). Pre-existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS-CoV-2 antigens in unexposed patients with T1D. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were collected from SARS-CoV-2 unexposed patients with T1D and healthy control subjects. SARS-CoV-2 specific T cells were identified in PBMCs by ex-vivo interferon (IFN)γ-ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. Results: T1D patients unexposed to SARS-CoV-2 exhibited higher rates of virus-specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT-8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT-8 autoantigens. Conclusions: The increased frequency of SAR-CoV-2- reactive T cells in T1D patients might protect against severe COVID-19 and overt infections. These results emphasise the long-standing association between viral infections and T1D.
2024
COVID‐19
SARS‐CoV‐2
T1D
autoimmunity
cross‐reactivity
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12317/94439
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