Celiac disease: how complicated can it get?

In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4+ T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4+ T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma

gc)Emerging technologies in upper gastrointestinal endoscopy and celiac disease.

Despite advances in our knowledge of celiac disease, the most current and authoritative recommendations conclude that diagnosis requires at least four biopsy specimens to be taken from the duodenal area. These recommendations are based on the perception that classic endoscopic markers are not adequate to target biopsy sampling to sites of villous damage in the duodenum. In the past few years, newly developed procedures and technologies have improved endoscopic recognition of the duodenum. These advances make possible the real-time recognition of the duodenal villous pattern during an upper endoscopy procedure, and thereby have the potential to optimize diagnostic accuracy. It is, therefore, reasonable to hypothesize that upper endoscopy might have a more incisive role in the diagnosis of celiac disease than merely providing a means of obtaining biopsy specimens for histological analysis. This Review highlights the new technologies in the field of upper endoscopy that could be helpful for the diagnosis of celiac disease, including the water-immersion technique, chromoendoscopy, high-resolution magnification endoscopy, optimal band imaging, optical coherence tomography and confocal endomicroscop