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T-cell response to gluten peptides similar in children, adults with celiac disease
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T-cells in children with celiac disease were found to respond to gluten peptides comparably to T-cells in adults with celiac disease in a recent study, suggesting that peptide-based treatments and diagnostics for adult patients may also be used in pediatric patients.
“Contrary to the prevailing theory, and to our surprise, we found that children reacted to the same key peptides of gluten that we had previously identified as toxic in adults with celiac disease,” Jason A. Tye-Din, PhD, from the Walter and Eliza Hall Institute of Medical Research, said in a press release. “The results of this study suggest that diagnostic tools and treatments currently being developed may be applicable in celiac disease patients of all ages.”
Tye-Din and colleagues collected blood samples to measure gluten-specific T-cell responses to a 3-day oral wheat challenge in 41 Australian children (median age, 9 years; 17 male) who adhered to a strict gluten-free diet for a minimum of 3 months, and evaluated whether gluten peptide recognition was comparable in T-cell clones from four adults.
Gluten-specific responses by T-cells were identified in 73% of the children, and their T-cells recognized the same peptides that were immunogenic to adults. Deamidation of peptides strengthened these responses, and age and time since diagnosis did not affect the extent of T-cell responses to dominant peptides. T-cell clones specific for dominant alpha- or omega-gliadin peptides reacted to wheat, rye and barely peptides similarly in children and adults, and alpha-gliadin-specific T-cells had similar biases in T-cell receptor usage in children and adults.
“We show the specificity of the gluten-specific T cell response reactivated by oral wheat challenge in children with [celiac disease] does not differ from adults,” the researchers wrote. “Stability of epitopes recognized by gluten-reactive CD4+ T cells after diagnosis of [celiac disease], whether in childhood or adult life, indicates clinical applications of gluten-derived T cell epitopes should be relevant to [celiac disease] patients of all ages.”
“This study demonstrates that, worldwide, most children and adults with celiac disease have very similar immune responses to gluten,” Leslie Williams, president and CEO of ImmusanT, said in a press release. “We will continue to pursue development of celiac disease diagnostic, therapeutic and preventive strategies that focus on gluten peptides consistently recognized by T cells, with the fresh knowledge that these advancements could be capable of reaching most people with celiac disease, regardless of their age.” – by Adam Leitenberger
Disclosure: Williams is an employee of ImmusanT. Tye-Din reports he is a co-inventor of patents pertaining to the use of gluten peptides in therapeutics, diagnostics and nontoxic gluten; a shareholder of Nexpep Pty Ltd; and a consultant to ImmusanT. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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