A Pilot Study of Preproinsulin Peptides Reactivity in Chinese Type 1 Diabetic Patients

Abstract

Type 1 diabetes (T1D) is an autoimmune disease in which auto-reactive T cells infiltrate the pancreatic islets and destroy insulin-producing β cells. Preproinsulin (PPI) is considered as an important autoantigen for developing T1D in Caucasian population, particularly in those bearing T1D associated susceptible alleles DRB1*04:01, DQA1*03:01 and DQB1*03:02. However, whether PPI could trigger similar responses in Chinese T1D patients remains elusive. Peripheral blood mononuclear cells from 19 newly diagnosed T1D (Mean Age =16.7yr) and 32 long term T1D patients (Mean Age =21.3yr) of Chinese Han nationality were isolated and stimulated by a pool of 13 different PPI peptides, which were synthesized according to epitope mapping of the full length PPI. PPI reactive T cells were measured by IFN-γELISPOT assay. Briefly, the mean values in wells with peptides were compared with those in background wells to derive a stimulation index (SI). A specific IFN-γresponse is defined as SI≥3. All patients showed a significant IFN-γresponse to OKT 3 stimulation, and 96% of patients showed positive responses to Pentaxim vaccine. However, we did not detect specific IFN-γresponse to PPI peptides with a range of concentrations (i.e., 1ug/ml to 100ug/ml). To confirm our results, 2 peptides (C19-A3, B9-23) with dominant epitopes known to be presented by DR4 and DQ8 were also tested. In agreement with the PPI peptide pool study, these 2 peptides did not induce specific IFN-γproducing T cells activity. This includes six patients with DQA1*03:01 and DQB1*03:02 alleles. This is the first report describing IFN-γresponse of T cells to overlapping human PPI peptides in Chinese T1D patient. It is worth knowing that, unlike the Caucasian T1D population, around 30% of Chinese T1D population uniquely consist the DRB1*09:01 allele (20% in our study population). Thus, the lack of specific response in our patient cohort suggests that PPI might not be the principal disease causing antigen in Chinese T1D due to the population heterogeneity. Disclosure Y. Xian: None. H. Xu: None. J. Lv: None. Y. Gao: None. W. Ren: None. Q. Huang: None. Z. Jiang: None. J. Yan: None. B. Yao: None. J. Weng: None.