A Type 1 Diabetes-related Protein from Wheat (Triticum aestivum)

Abstract

The development of autoimmune type 1 diabetes involves complex interactions among several genes and environmental agents. Human patients with type 1 diabetes show an unusually high frequency of wheat gluten-sensitive enteropathy; T-cell response to wheat proteins is increased in some patients, and high concentrations of wheat antibodies in blood have been reported. In both major models of spontaneous type 1 diabetes, the BioBreeding (BB) rat and non-obese diabetic mouse, at least half of the cases are diet-related. In studies of BB rats fed defined semipurified diets, wheat gluten was the most potent diabetes-inducing protein source. A major limitation in understanding how wheat or other dietary antigens affect type 1 diabetes has been the difficulty in identifying specific diabetes-related dietary proteins. To address this issue, we probed a wheat cDNA expression library with polyclonal IgG antibodies from diabetic BB rats. Three clones were identified, and the intensity of antibody binding to one of them, WP5212, was strongly associated with pancreatic islet inflammation and damage. The WP5212 putative protein has high amino acid sequence homology with a wheat storage globulin, Glb1. Serum IgG antibodies from diabetic rats and humans recognized low molecular mass (33-46 kDa) wheat proteins. Furthermore, antibodies to Glb1 protein were found in serum from diabetic patients but not in age-, sex-, and HLA-DQ-matched controls. This study raises the possibility that in some individuals, type 1 diabetes may be induced by wheat proteins. Also, it provides a first candidate wheat protein that is not only antigenic in diabetic rats and human patients but is also closely linked with the autoimmune attack in the pancreas.

The Impact of Diet Wheat Source on the Onset of Type 1 Diabetes Mellitus—Lessons Learned from the Non-Obese Diabetic (NOD) Mouse Model

“…However, there may be other wheat proteins involved in the onset of T1D. For example, a wheat globulin protein Glb1 was identified as a diabetic related autoantigen using serum from diabetic BioBreeding rats [34]. Antibodies to this protein were also found in the serum of diabetic patients [35].…”

Diagonal two-dimensional electrophoresis (D-2DE): a new approach to study the effect of osmotic stress induced by polyethylene glycol in durum wheat (Triticum durum Desf.)

“…A recent study identified Globulin 3A as the first candidate wheat protein to be associated with the development of Type 1 diabetes (T1D) [29].…”

A Potential Link between Environmental Triggers and Autoimmunity

“…In association with various autoimmune disorders, wheat proteins and, more specifically, gluten, have received significant attention [98–100]. Indeed, it has been demonstrated that a wheat-based diet induces not only Th1-type cytokine bias in the gut but also increased T-cell reactivity to gluten, with a higher frequency of diabetes [99–101]. In addition to diabetes, it has been shown that celiac disease (CD) is associated with various extraintestinal autoimmune disorders that involve the thyroid, joints, heart, skin, pancreas, bone, liver, reproductive organs, and the nervous system [102–112].…”