Proline-rich gluten peptides

Proline-rich gluten peptides are fragments of wheat, barley, and rye proteins that are resistant to degradation by human digestive enzymes due to their high proline and glutamine content (Scherf et al., 2016). The most prominent of these is the 33-mer alpha-gliadin peptide, which is highly immunogenic in individuals with Celiac disease (Shan et al., 2002). Upon entering the lamina propria of the small intestine, these peptides are deamidated by tissue transglutaminase 2 (TG2), significantly increasing their affinity for HLA-DQ2 and HLA-DQ8 receptors on antigen-presenting cells (Sollid, 2002). This process initiates an inflammatory T-cell response, resulting in villous atrophy, crypt hyperplasia, and malabsorption (Lebwohl et al., 2018). Therapeutic interventions, such as latiglutenase and TAK-062, aim to enzymatically degrade these peptides in the stomach or duodenum to prevent the downstream immune cascade (Pultz et al., 2021). Additionally, detection of these peptides in excreta serves as a biomarker for monitoring dietary adherence and the efficacy of gluten-targeted therapies (Moreno et al., 2017).

Other names

Gluten-derived proline-rich peptidesGliadin-derived peptidesImmunogenic gluten peptides33-mer gliadin peptideGluten immunogenic peptides (GIP)

Enzymatic degradation of immunogenic gluten peptides into non-toxic fragments using exogenous proteases or sequestration by non-absorbable polymers to prevent epithelial translocation.