Tissue transglutaminase generates deamidated epitopes on gluten, increasing reactivity with hydrolyzed wheat protein–sensitized IgE

• Published in: Journal of allergy and clinical immunology 2013-12, Vol.132 (6), p.1436-1438.e4
• Main Authors: Nakamura, Ryosuke, PhD, Nakamura, Rika, PhD, Sakai, Shinobu, PhD, Adachi, Reiko, PhD, Hachisuka, Akiko, PhD, Urisu, Atsuo, MD, PhD, Fukutomi, Yuma, MD, PhD, Teshima, Reiko, PhD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Allergens - immunology; Allergies; Allergy and Immunology; Antigens; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; Enzymes; Epitopes, B-Lymphocyte - immunology; Female; Food allergies; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gluten; Glutens - chemistry; Glutens - immunology; GTP-Binding Proteins; Humans; Hydrolysis; Immunoglobulin E - metabolism; Infant; Male; Medical sciences; Methods; Middle Aged; Patients; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Serologic Tests - methods; Transglutaminases - immunology; Triticum; Wheat Hypersensitivity - diagnosis; Wheat Hypersensitivity - immunology; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.07.017

Many celiac disease studies have shown that digestion-resistant peptide fragments of wheat gluten can access the lamina propria and be deamidated by tTG.7 However, it is also well known that gluten is deamidated during hydrolysis under acidic and heating conditions.8 Therefore we performed limited proteolysis of gluten, tTG-Glu, and Glp19S with the endoproteinase Glu-C, which cleaves at glutamic acid residues in peptides (see the Methods section in this article's Online Repository). tTG treatment induced a mobility shift of gluten with a smear pattern, which was completely eliminated by Glu-C treatment (see Fig E2 in this article's Online Repository at www.jacionline.org). Wheat Gluten [omega]-5 gliadin 0.01% Glp19S 0.1% Glp19S Wheat Bread Positive control HWP-sensitized subjects 1 55/F 4.38 6.15 0.34 123 3 9 0 0 3 Yes WDEIA (history) 2 41/F 21.8 36.2 7.01 285 5 8 7 5 7 Yes WDEIA (history) 3 51/F 2.28 3.65 0.34 210 5 ND 3 2 4 Yes WDEIA (history) 4 42/F 23.4 31.4 2.06 4,050 3 ND 0 0 4 Yes WDEIA (history) 5 23/F 1.79 3.12 0.34 1,510 3 9 0 0 6 Yes WDEIA (history) Patients with PedWA 1 5/M 100 ND ND 800 ND ND ND ND ND No FA (history) 2 1/F 92.8 ND ND 2,900 ND ND ND ND ND No FA (history) 3 2/M 100 ND ND 23,221 ND ND ND ND ND No FA (history) 4 3/M (Class 4) 66.6 0.4 512 ND ND ND ND ND No FA with anaphylaxis (history) 5 1/F 17.6 17.6 ND 191 ND ND ND ND ND No FA (OFC) 6 7/M 11.4 20 0.49 ND ND ND ND ND ND No FA (OFC) Healthy control subjects 1 24/F ND ND ND 22 ND ND ND ND ND No None 2 61/F ND ND ND 37 ND ND ND ND ND No None 3 55/F ND ND ND 17 ND ND ND ND ND No None 4 55/M ND ND ND 17 ND ND ND ND ND No None Table E1 Serologic and clinical features of enrolled wheat allergic subjects For SPTs, Glp19S (a gift from Katayama Chemical Industries, Osaka, Japan) and commercial wheat and bread allergen extracts (Torii Pharmaceutical, Tokyo, Japan) were used.