Stefano Guandalini1, Mala Setty. 1. Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. sguandalini@peds.bsd.uchicago.edu
Abstract
PURPOSE OF REVIEW: Research in celiac disease is unraveling new findings at a high rate, and major advances seem to occur in all areas such as genetics, environmental factor, pathophysiology, and even prospective therapeutic implications. RECENT FINDINGS: New insight is being gained into the interplay between genetic and environmental factors causing celiac disease. In addition to the known human leukocyte antigen haplotypes, genome-wide studies have now identified additional susceptibility loci and the majority of newly discovered risk regions harbor genes controlling immune pathways. The mechanism of translocation of gliadin peptides across the intestinal barrier has been the subject of much investigation, and there is now evidence that the toxic 33-mer peptide can also be translocated transcellularly. As for the paracellular route, this appears to be enhanced by gliadin's stimulation of zonulin release. The growing role of the innate immunity is being recognized and the increased expression of some Toll-like receptors appears to delineate a new inherent defect in this branch of innate immunity. Finally, new perspectives are opening in the treatment of celiac disease based on new detoxified grains, enzymatic degradation of gluten, and prevention of its crossing the mucosal barrier. SUMMARY: The pace of new knowledge in this 'ancient' disease is very fast, and this review outlines the principal lines of such exciting developments.
PURPOSE OF REVIEW: Research in celiac disease is unraveling new findings at a high rate, and major advances seem to occur in all areas such as genetics, environmental factor, pathophysiology, and even prospective therapeutic implications. RECENT FINDINGS: New insight is being gained into the interplay between genetic and environmental factors causing celiac disease. In addition to the known human leukocyte antigen haplotypes, genome-wide studies have now identified additional susceptibility loci and the majority of newly discovered risk regions harbor genes controlling immune pathways. The mechanism of translocation of gliadin peptides across the intestinal barrier has been the subject of much investigation, and there is now evidence that the toxic 33-mer peptide can also be translocated transcellularly. As for the paracellular route, this appears to be enhanced by gliadin's stimulation of zonulin release. The growing role of the innate immunity is being recognized and the increased expression of some Toll-like receptors appears to delineate a new inherent defect in this branch of innate immunity. Finally, new perspectives are opening in the treatment of celiac disease based on new detoxified grains, enzymatic degradation of gluten, and prevention of its crossing the mucosal barrier. SUMMARY: The pace of new knowledge in this 'ancient' disease is very fast, and this review outlines the principal lines of such exciting developments.
Authors: Henry J McSorley; Soraya Gaze; James Daveson; Dianne Jones; Robert P Anderson; Andrew Clouston; Nathalie E Ruyssers; Richard Speare; James S McCarthy; Christian R Engwerda; John Croese; Alex Loukas Journal: PLoS One Date: 2011-09-16 Impact factor: 3.240