Recent Advances in Celiac Disease

Abstract

Recent diagnostic advances have demonstrated that celiac disease is relatively common although most patients have less florid symptoms than previously recognised. The mucosal lesion of this autoimmune disorder depends on both adaptive and innate immune responses. The characteristic antibodies to tissue transglutaminase-2 (tTG-2) and deamidated gliadin peptides may be produced in persons possessing the relevant HLA-DQ genotypes if intact gliadin peptides can penetrate the epithelial barrier to reach antigen presenting cells. Progression from celiac autoimmunity to overt disease may depend on innate immune mechanisms, not HLA-restricted, where IL-15 is generated within the epithelial compartment. A specific innate immune response previously thought restricted to invertebrates, the encapsulation reaction, may contribute to mucosal volume expansion through recruitment of syndecan-expressing leukocytes and stimulated matrix production. It is notable that tissue transglutaminase is critical in this reaction in insects, and that the very few insects that can predate wheat, possess specific salivary or intestinal enzymes that degrade gluten. Animal models in HLA-DQ transgenic mice suggest that the microbial flora of the intestine may play a role in host responses and modulate the evolution of the disease. This suggests that therapeutic modulation of the microbiome may contribute to management of celiac disease. In developing world countries, there is a potential difficulty in histological diagnosis because of the widespread incidence of environmental enteropathy amongst apparently healthy children. Thus, recognition of local patterns of enteropathy will be important for histopathologists, and high titre tTG-2 autoantibody titres may hold considerable diagnostic significance.

Intraepithelial lymphocytes, scores, mimickers and challenges in diagnosing gluten-sensitive enteropathy (celiac disease)

“…MALT of the gut is, indeed, crucial for the immunology and preservation of the microbiome[ 1 , 18 , 25 ]. Lymphocytes are recognized in the duodenal surface epithelium, because of some characteristics that allow them to be differentiated from the epithelial cells.…”

“…False-negative aTTG results may be seen in patients harbouring IgA deficiency, which is detected in 1/10 of the GSE patients and testing of IgG isotype of aTTG is mandatory. To date, deamidated gliadin peptide (DGP) seems to have better sensitivity in detecting early-stage GSE as compared to the TTG and EMA, and has been proposed to be the first line of investigation in IgA deficient patients (see below for differences among gastroenterological societies)[ 25 , 41 , 44 , 45 ]. False-positive results may occur in the setting of patients suffering from inflammatory bowel disease (IBD), primary biliary cirrhosis, cardiovascular disease, autoimmune enteropathy and other immune-mediated disorders[ 25 , 29 , 41 , 44 , 46 ].…”

“…Autoimmune enteropathy (AIE) is another GSE-mimicker because it is characterized by villous atrophy unresponsive to a GFD[ 25 , 110 ]. The histological evidence of enteropathy, a lack of any triggering food protein, anti-enterocyte antibodies as well as persistent diarrhoea after prolonged fasting and presence of organ-specific serum antibodies are essential for the diagnosis of this entity.…”

The Role of Molecular Typing for DQ2 and DQ8 Alleles Using Polymerase Chain Reaction Amplification in Children with Autoimmune Conditions

“…These haplotypes are mandatory, but insufficient to cause the disease without another factors intervention. Thereby DQ2 and DQ8 haplotypes demonstrated a negative predictive value of 100% for the diagnosis of gluten enteropathy [34].…”

Editorial: Striving for Excellence in Pediatric Gastroenterology Care — A Continuous Effort

“…The first article is on BRecent advances in celiac disease [ 1]. Celiac disease (CD) is a very common cause of chronic diarrhea and has a prevalence of~1% in the general population of North India [2].…”