Humoral and cellular immune responses to IGF-2 in type 1 diabetes (128.21)

Abstract

Abstract Background IGF-2 is the dominant member of insulin family expressed in the thymus, Igf2 expression contributes to complete tolerance of insulin, and Igf2 transcription is defective in the thymus of diabetes-prone BB rats. Objectives To evaluate the immunological tolerance to IGF-2 in T1D patients; andTo analyse the type of cellular response induced by IGF-2 B11-25, the homologous sequence of Insulin B9-23, a major T1D auto-antigen. Results Using a sensitive and specific radio-binding assay, the presence of autoantibodies against IGF-2 was investigated in 100 newly diagnosed T1D patients and 100 healthy controls. No significant difference appeared between the two groups.We also investigated the profile of IL-10/IFN-γ secretion following presentation of Insulin B9-23 and IGF-2 B11-25 to PBMCs from T1D patients and healthy controls. Compared to Insulin B9-23 in ELISpot, ELISA and real-time RT-PCR, the presentation of IGF-2 B11-25 induced a regulatory/tolerogenic profile with a significantly higher increase of IL10 transcription and IL-10 secretion. Conclusions The very strong tolerance to IGF-2 is associated to active regulatory properties that might be exploited for development of a tolerogenic self-vaccine against T1D. (Supported by the Belgian NFSR, Walloon Region TOLEDIAB project, and FP6 Euro-Thymaide Integrated Project)