A pilot study of preproinsulin peptides reactivity in Chinese patients with type 1 diabetes

Background The aim of our study is to investigate whether preproinsulin (PPI) could trigger a proinflammatory CD4(+) T cell response in Chinese patients with type 1 diabetes (T1D). Methods Peripheral blood mononuclear cells were stimulated by a pool of 13 PPI peptides. Additional five PPI peptides previously proved to be antigenic in other cohorts of patients with T1D were also used. PPI reactive T cell responses were measured by interferon (IFN)-gamma ELISPOT assay. Results Fifty-one Chinese patients with T1D were enrolled in this study and 72.34% of them were positive for at least one islet autoantibody. The stimulation index (SI) value of IFN-gamma response to PPI peptide pool or peptides with dominant epitopes was below 3 in patients when SI >= 3 was used as the positive cut-off value. Two peptides (B9-23 and C19-A3) restricted to DQ8 or DR4 molecule failed to induce positive IFN-gamma response in patients with high-risk HLA-DQ8 or HLA-DR4/DR9 alleles. RNA-seq analysis of PPI specific CD4(+) T cell lines further showed that most of the IFN-gamma associated genes remained unchanged. Conclusions This is the first report of CD4(+) T cell epitope mapping of PPI in Chinese T1D. The lack of positive IFN-gamma response to PPI peptides indicates that PPI might not be the principal antigenic candidate for autoreactive CD4(+) T cells in Chinese T1D. Therefore, the efficacy of PPI-based immunotherapies in attenuating proinflammatory CD4(+) T cell response requires further investigation.