Coeliac disease, low immunotoxic foods

Coeliac disease widespread in the western world, Eastern Europe and Asia at rates of 1% and 1.44% of north Indians. Armstrong, Hegade and Robins 2012 write that genes related to coeliac disease also overlap with other autoimmune diseases. Human leukocyte antigen genotyping increases sensitivity in detecting coeliac disease in atypical cases. The authors also describe proinflammatory pitfalls of vitamin A supplementation in active coeliac disease. [1]

Genetic testing for Coeliac disease
The combination of a tTG antibody more than 100U/ml and symptomatic response to a gluten-free diet (GFD) avoids the need for a diagnostic biopsy. Antibodies against deamidated gliadin peptides (α-DGP) have a high sensitivity and specificity for coeliac disease.

Coeliac disease is extremely unlikely to affect persons who test negative for both HLA-DQ2 and HLA-DQ8. Susceptibility for coeliac disease was found to be linked to HLA-DQ2  and  HLA-G I . Protection of the disease is linked to NLRP3, however,  NLRP1 predisposes to the development of the disease.

Testing oat cultivar for gluten-free diet [2]
Comino et al. 2011 examined differences in monoclonal antibodies moAb G12  against the main immunotoxic 33-mer peptide (A1 and G12).   The oat cultivars presented different reactivity and one cultivar had no detectable reactivity. The immunogenicity was determined with isolated peripheral blood mononuclear T cells from patients with CD. A direct correlation of the reactivity with G12 and the immunogenicity of the cereal cultivar was confirmed. The authors suggest to use  moAbG12 antibody reaction to find immunologically safe oat cultivars for a gluten-free diet.

Identifying hordein fractions in barley to create hordein-free barley [3]
Tanner et al. 2010 identified the immunotoxicity of hordeins from experimental barley lines using peripheral hordein-specific blood T-cells from coeliac volunteers under oral barley challenge

The authors found that D- and C-hordeins were the most immunotoxic of all prolamin fractions , and barley lines lacking B- and C-hordeins had a 5-fold reduced hordein-content, and a 20-fold reduced immunotoxicity as found in wild-type barley. Fresh activated T-cells may be used to identify low  B- and C-hordeins barley to create of hordein-free barley.

Germinating enzyme pretreatment of coeliac-safe food products [4]
Gluten-free diet excludes food products containing wheat, rye and barley. In a study of Stenman et al. 2010 the immunotoxicity of  rye secalin  in vitro in intestinal epithelial cell models was found to be comparable to wheat gliadin. This confirms the need to exclude rye from the coeliac patient's diet.

Pretreatment of rye with germinating barley enzymes provided the most efficient degradation of secalin and gliadin peptides, reducing all toxic reactions induced by secalin. The authors suggest further studies  to use such enzymes as medical treatment of coeliac disease, or to use it for the production of coeliac-safe food products.

Transgenic wheat plants  with low toxicity [5] 
Gil-Humanes et al. 2010 down-regulated the expression of gliadins in transgenic bread wheat using a set of RNAi hairpin constructs expressed in the endosperm, obtaining wheat lines with very low levels of toxicity.

[1] Armstrong MJ, Hegade VS, Robins G: Advances in coeliac disease. Curr Opin Gastroenterol. 2012 Mar;28(2):104-12.
http://www.ncbi.nlm.nih.gov/pubmed/22123644

[2] Comino I, Real A, de Lorenzo L, Cornell H, López-Casado MÁ, Barro F, Lorite P, Torres MI, Cebolla A, Sousa C: Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease. Gut. 2011 Jul;60(7):915-22.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112367/?tool=pubmed

[3] Tanner GJ, Howitt CA, Forrester RI, Campbell PM, Tye-Din JA, Anderson RP: Dissecting the T-cell response to hordeins in coeliac disease can develop barley with reduced immunotoxicity. Aliment Pharmacol Ther. 2010 Nov;32(9):1184-91. doi: 10.1111/j.1365-2036.2010.04452.x
http://www.ncbi.nlm.nih.gov/pubmed/21039679

[4] Stenman SM, Lindfors K, Venäläinen JI, Hautala A, Männistö PT, Garcia-Horsman JA, Kaukovirta-Norja A, Auriola S, Mauriala T, Mäki M, Kaukinen K: Degradation of coeliac disease-inducing rye secalin by germinating cereal enzymes: diminishing toxic effects in intestinal epithelial cells. Clin Exp Immunol. 2010 Aug;161(2):242-9.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2909406/?tool=pubmed

[5] Gil-Humanes J, Pistón F, Tollefsen S, Sollid LM, Barro F: Effective shutdown in the expression of celiac disease-related wheat gliadin T-cell epitopes by RNA interference. Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):17023-8.
http://www.ncbi.nlm.nih.gov/pubmed/20829492