1676-P: Immune Responses to Insulin B:9-23–Related Peptides Were Observed in Fulminant Type 1 Diabetes

Most type 1 diabetes (T1D) is considered to be a T helper (Th)-1 type anti-islet autoimmune disease. Recently, we reported that the immune responses to insulin B9-23-related peptides were strengthened in T1D. Meanwhile, fulminant T1D (FT1D), a novel subtype of T1D characterized by extremely rapid onset and complete deficiency of insulin due to destruction of pancreatic β-cells, has been believed to be caused by viral infection as the etiological mechanism; but, whether the etiology associates with anti-islet immune reactions or not remains unknown. This study aims to investigate whether the immune responses to insulin B9-23-related peptides associate with FT1D. Peripheral mononuclear cells (MNCs) were obtained from 72 patients with acute-onset T1D (AT1D; age, 46.2 ± 14.7 y/o; disease duration (DD), 8.8 ± 10.7 years), 15 patients with FT1D (age, 46.1 ± 14.2 y/o; DD, 4.7 ± 8.2 years) and 25 patients with type 2 diabetes (T2D; age, 63.3 ± 13.1 y/o; DD, 17.0 ± 10.2 years). The MNCs were stimulated by insulin B9-23, B10-24, B11-25 and B12-26 for 24 hours. Subsequently, ELISpot assay was performed for investigating a frequency of interferon (IFN)-gamma (g)-producing MNCs. The maximum number of IFN-g spots in the peptides-related data of each subject was used for analysis and expressed by the number of spot-forming cells (SFCs) per 2.5×10⁵ cells. As a result, the spot number was significantly higher in AT1D (2.6 ± 3.0 SFCs) and FT1D (2.5 ± 2.6 SFCs) as compared to T2D groups (1.0 ± 1.1 SFCs) (P <0.05 by t-test), suggesting that Th1-type immune responses to insulin B9-23-related peptides were observed in FT1D, and that the degree of response was comparable in the two groups, suggesting the association between anti-islet autoimmunity and FT1D. This cross-sectional study could not reveal an association between the Th1-type immune responses and disease activity which may be inferred from the residual serum C-peptide levels or disease duration, which warrant further investigation by accumulating more subjects.