Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

A lower frequency of insulin peptide B9-23-reactive IL-10-producing cells observed in type 1 diabetic patients with HLA-DRB1*09:01. (#101)

Yoichi Oikawa 1 , Yutaka Hattori 2 , Akira Shimada 1
  1. Tokyo Saiseikai Central Hospital, Tokyo, Japan
  2. Division of Clinical Physiology and Therapeutics, Keio University Faculty of Pharmacy, Tokyo, Japan

BACKGROUND: Type 1 diabetes (T1D) is considered as a Th1-type anti-islet autoimmune disease. Insulin is one of the major islet-associated antigens, and insulin peptide B9–23 (ins B9-23) is considered as a main epitope of T cells both in mouse and human T1D. Meanwhile, HLA-DRB1*09:01 as well as HLA-DRB1*04:05 is an important susceptible HLA genotype in type 1 diabetes in Japan. However, the relationship between immune responses to ins B9-23 and HLA-DRB1*09:01 in patients with T1D remained to be elucidated.
AIM: The aim of this study is to investigate the cellular immune responses to ins B9-23 in T1D with HLA-DRB1*09:01, and compared with T2D with HLA-DRB1*09:01.
METHODS: Cytokines (IFN-gamma and IL-10) secretion from peripheral mononuclear cells against responses to insulin or insulin peptide (ins B9–23) were studied by enzyme-linked immunospot (ELISPOT) assay in 23 patients with T1D and 26 patients with T2D. All patients were treated with insulin. Genotyping of HLA DRB1 was also performed.
RESULTS: In the subjects with HLA-DRB1*09:01, but not those without it, a frequency of ins B9-23-reactve IL-10-producing cells was significantly lower in the patients with T1D than those with T2D. Meanwhile, there was no significant difference in a frequency of ins B9-23-reactive IFN-gamma-producing cells between subjects with T1D and T2D, in spite of the presence or absence of HLA-DRB1*09:01.
DISCUSSION and CONCLUSIONS: These findings suggest that a decrease in ins B9-23-reactive IL-10-producing cells may be associated with the development of anti-islet autoimmunity and T1D exclusively in the subjects with HLA-DRB1*09:01. According to an analysis by using T Cell Epitope Prediction Tools, a binding affinity of ins B9-23 to HLA-DRB1*09:01 is low; this finding may partly account for the possibility that, in the subjects with HLA-DRB1*09:01, ins B9-23-reactive IL-10-producing cells is less prone to expand under the condition of the presence of anti-islet autoimmunity.