Immune reactivity to a homologue of wheat storage globulin, Glb1 in human type 1 diabetes

Abstract

Type 1 diabetes (T1D) is a T cell mediated autoimmune disease dependent on gene-environment interaction. A wheat storage globulin with 80% amino acid homology to Glb1 (referred to as Glb1), was identified as the first candidate diabetes-related wheat protein in diabetes-prone rats. Glb1 antibodies were also found in pooled diabetic serum (MacFarlane et al., JBC, 2003). In this study, we evaluated the response of peripheral blood T cells to recombinant Glb1 protein in T1D patients and healthy controls. T cell response was measured using a CFSE proliferation assay and reported as cell division index (CDI). Th1 and Th2 cytokines were analyzed using cytometric bead arrays. Glb1 antibodies were evaluated by ELISA. T1D patients showed a higher mean CDI in response to Glb1. More than 1/3 of patients were responders (CDI > control mean + 3 SD). Cytokine analysis of the culture supernatant from Glb1-stimulated PBMC of patients showed a Th1 response, with IFN-γ most abundant. Approximately 25% of patients displayed Glb1 antibody levels higher than the control group mean + 2 SD. This study demonstrates high T cell reactivity with a Th1 response and antibodies to Glb1 in a subset of T1D patients. Further study is required to determine whether Glb1 plays a direct role in the pathogenesis of T1D or whether immune reactivity against this protein is a biomarker of a related process. (Supported by JDRF and CIHR)