Gianfrani C et al. (2007) Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology 133: 780–789

The development by an Italian research team of a method to reduce the immunogenicity of gluten could be of great benefit to people with celiac disease. Celiac disease is caused by an immune reaction to digestive products of gluten in people expressing human leukocyte antigen (HLA) DQ2 and DQ8 heterodimers. Binding of certain gluten-derived peptides to DQ2 or DQ8 molecules results in an inflammatory response mediated by interferon-γ. In particular, deamidation of certain glutamine residues to glutamate by intestinal tissue transglutaminase enzyme results in more-acidic peptides with greater affinity for DQ2 and DQ8, and consequently a more severe T-cell-mediated inflammatory response. Gianfrani et al. found that blocking these glutamine residues with lysine methyl ester (Lys-CH3) strongly inhibited the immune response to immunotoxic peptides in T cells from patients with celiac disease.

A transamidation reaction attached Lys or Lys-CH3 to a glutamine residue of α-gliadin p56–68, an immunotoxic derivative of gluten. The modified peptide had greatly reduced affinity for the DQ2 heterodimer, and significantly reduced interferon-γ release (indistinguishable from a negative control) from T cells of patients with celiac disease compared with native or deamidated peptides.

Treating wheat flour with microbial transglutaminase in the presence of Lys-CH3 neutralized the immunotoxicity of the digested products. Gluten extracts from treated flour produced minimal interferon-γ release from celiac disease T cells; by contrast, untreated extracts evoked a strong response.

The results suggest that wheat products can be enzymatically modified to eliminate immunotoxic effects in individuals with celiac disease.