Coeliac disease: immunogenicity studies of barley hordein and rye secalin‐derived peptides

Abstract

Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.

Celiac Disease and Autoimmune Diseases

“…Malabsorption of calcium and vitamin D lead to osteoporosis, pathological fractures, bone and secondary hyperparathyroidism. 1,2 CD has a range of symptoms. The most common symptoms include diarrhea, bloating, weight loss, and steatorrhea (fatty diarrhea).…”

“…Other symptoms are fatigue, growth disorder in children, atrophy and muscle weakness. 1,2 It is usually during infancy or early childhood (two weeks until one year old) that CD begins. It is possible that symptoms appear when children first begin to eat foods that contain gluten.…”

“…In adults, symptoms may gradually emerge within a few months or even years. 1 An increased prevalence of autoimmune disorders including autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases, and inflammatory bowel disease are detected in celiac patients.…”

“…1,2 Some celiac patients do not have symptoms; because the healthy part of the intestine does not absorb enough nutrients to prevent symptoms' development. As just symptoms, some adults have fatigue and anemia.…”

“…High incidences of cancers are seen in celiac patients. 1,2 Other symptoms are amenorrhea, infertility, pyloric stenosis, ecchymosis and petechia (lack of vitamin K), edema, and dermatitis herpetiformis. Dermatitis herpetiformis is an au toimmune blistering disorder that is often associated with a gluten-sensitive enterop athy (GSE).…”