Allergy to deamidated gluten in patients tolerant to wheat: specific epitopes linked to deamidation

Abstract

Background Gluten proteins can be modified by deamidation to enhance their solubility and technological applications. However, severe allergic reactions have been reported after the consumption of food products containing deamidated gluten (DG) in subjects tolerant to wheat. This work aimed to characterize allergen profiles for these patients in comparison with those of patients allergic to wheat and to identify IgE‐binding epitopes. Methods Sera were obtained from 15 patients allergic to DG and from nine patients allergic to wheat proteins (WP). IgE‐binding profiles were characterized both in ELISA and in a humanized rat basophilic leukaemia (RBL) cell model. Epitopes were mapped on γ‐ and ω2‐gliadin sequences by Pepscan, and effect of glutamine/glutamic acid substitutions was studied. Results Compared to the heterogeneous pattern of allergens detected by IgE from patients allergic to WP, responses of patients allergic to DG were homogeneous. In ELISA, all the sera displayed IgE binding to deamidated γ‐ and ω2‐gliadins and deamidated total gliadins, frequently with high concentrations. These modified proteins induced RBL degranulation with most of the sera from DG‐allergic patients. A consensus epitope was found on native γ‐ and ω2‐gliadins (QPQQPFPQ); it was repeated several times in their sequences. The substitution of two or three glutamines of this epitope into glutamic acid at positions Q3 or Q4 and Q8 (QPEEPFPE) increased its recognition the best. Conclusion Allergy to DG is a separate entity from wheat allergy. It can be evidenced by strong IgE binding to deamidated gliadins or peptides of the type QPEEPFPE.

An Animal Model for Wheat Allergy Skin Sensitisation: A Comparative Study in Naive versus Tolerant Brown Norway Rats

“…or orally with acid-hydrolysed gluten developed specific IgG 1 responses with a binding capacity different from that in rats sensitised with unmodified gluten. This is in agreement with Denery-Papini et al [41], who found that IgE from patients allergic to deamidated gluten had the strongest reaction, with an epitope where 2 or 3 of 4 glutamines were changed to glutamate due to deamidation.…”

Acid Hydrolysis of Wheat Gluten Induces Formation of New Epitopes but Does Not Enhance Sensitizing Capacity by the Oral Route: A Study in “Gluten Free” Brown Norway Rats

“…This is in line with results presented by Denery-Papini et al . [33] who found that IgE from patients allergic to gluten deamidated by heating and acid treatment reacted strongest with an epitope where two or three glutamines were deamidated to glutamic acid. These data supports our finding, that acid hydrolysis of gluten induces formation of new epitopes.…”

Combining Analyses of Basophil Allergen Threshold Sensitivity, CD-sens, and IgE Antibodies to Hydrolyzed Wheat, ω-5 Gliadin and Timothy Grass Enhances the Prediction of Wheat Challenge Outcome

“…Further research is needed to clarify if the raised HWP-specific IgE can be a result of cross-reactions of wheat-specific IgE to HWP or possibly be a double sensitization by wheat and HWP. In addition, Denery-Papini et al [30] showed recently that this type of allergy to deaminated gluten has a separate entity, which is characterized by a homogeneous IgE-Ab response, and is a direct consequence of present technologies applied to industrial food products. We found that most children with IgE-Ab <8 kU A /l to HWP did not react in CD-sens to HWP in comparison to those with higher IgE-Ab levels.…”