Objective Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD.
Design 42 children with human leucocyte antigen (HLA)-DQ2.5+ (aged 3–17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD.
Results 90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults.
Conclusions Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.
- food intolerance mechanisms
- CD4+ T cell
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Contributors MH conceived the study, designed and performed experiments, analysed and interpreted data, and wrote the manuscript. AR, CJ and KW performed experiments and analysed the data. CP performed patient recruitment, feeding studies, symptom diary collection and sample collection. NL designed experiments and interpreted the data. DC performed paediatric patient diagnoses and recruitment. JT-D conceived the study, designed the experiments, interpreted data and wrote the manuscript.
Funding The laboratory was supported by the National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme and Victorian State Government Operational Infrastructure Support.
Competing interests MH and JT-D are co-inventors of patents pertaining to the use of gluten peptides in therapeutics, diagnostics and nontoxic gluten. DC and JT-D hold shares in Nexpep Pty Ltd. JT-D is an advisor to ImmusanT Inc. The other authors do not have any conflicts to disclose.
Patient consent for publication Not required.
Ethics approval The study was approved by the human research ethics committees of the Royal Children’s Hospital (32018), the Walter and Eliza Hall Institute (03/04) and Melbourne Health (2003.009). All participants and/or their parents provided written informed consent.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.
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