Immune Reactivity to a Glb1 Homologue in a Highly Wheat-Sensitive Patient With Type 1 Diabetes and Celiac Disease
- Majid Mojibian, MLD12,
- Habiba Chakir, PHD12,
- Amanda J. MacFarlane, PHD12,
- David E. Lefebvre, BSC12,
- John R. Webb, PHD2,
- Claire Touchie, MD3,
- Jacob Karsh, MD3,
- Jennifer A. Crookshank, MSC1 and
- Fraser W. Scott, PHD12
- 1Molecular Medicine, Ottawa Health Research Institute, Ottawa, Ontario, Canada
- 2Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada
- 3Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada
- Address correspondence and reprint requests to Fraser W. Scott, Molecular Medicine, Ottawa Health Research Institute, 501 Smyth Rd., Ottawa ON, K1H 8L6. E-mail: fscott{at}ohri.ca
- Glb1, wheat storage globulin-1
- IFN-γ, γ-interferon
- IL, interleukin
- PBMC, peripheral blood mononuclear cell
In type 1 diabetes, the environmental factors that induce the patient’s immune system to attack and destroy the insulin-secreting β-cells are not known. There is evidence that some cases of type 1 diabetes could be wheat related (1,2). Exposure to wheat protein was a risk factor for development of type 1 diabetes autoantibodies in high-risk infants (1,2), and as many as 2–8% of type 1 diabetic patients have celiac disease (3), also known as gluten-sensitive enteropathy. Some studies in animals also suggest that wheat could be involved (4–7). Recently, a wheat protein, WP5212, with 80% amino acid homology to wheat storage globulin-1 (Glb1), was identified as the first candidate diabetes-related wheat protein in diabetes-prone rats (5). We report the case of a highly wheat-sensitive patient with type 1 diabetes/celiac disease who displayed strong antibody and T-cell responses to this protein.
A 28-year-old Caucasian female, with a 10-year history of type 1 diabetes, presented early in 1999 with diarrhea followed by oral ulcerations and severe lip swelling (Fig. 1A). At diagnosis, anti-gliadin IgG, anti-tissue transglutaminase IgA, and endomysial antibodies were present. The diarrhea and lip swelling improved initially with a gluten-free diet, but the symptoms recurred within a few months with worsening of the oral ulcerations, lip swelling, and continued diarrhea. Despite 6 months of a standard gluten-free diet, a duodenal biopsy showed mild villous atrophy. Colonoscopy and small bowel follow-through were normal. Biopsy of the oral lesion showed noncaseating granulomas, which were negative for IgG, IgA, IgM, C3, fibrinogen, and albumin with no histological evidence of eosinophilia. The patient was evaluated by a clinical allergist. Skin prick tests for several foods, including wheat, were all negative, and there was no evidence of IgE-mediated food allergy. In December 2001, the mucosa of her lower lip …
