The gliadin-CFTR connection: new perspectives for the treatment of celiac disease

Familial loss-of-function mutations of the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) channel protein cause cystic fibrosis (CF), the most frequent inherited life-threatenin...
Source: Italian Journal of Pediatrics - Category: Pediatrics Authors: Tags: Commentary Source Type: research

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In conclusion, the incidence of M abscessus does not seem to be increasing in non-CF patients in our institution. There may be an epidemiological link with acid suppression and reflux disease, this hypothesis has been previously reported in patients with CF.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
Pancreatic exocrine insufficiency occurs when there is insufficient production or delivery of pancreatic enzymes required for the digestion and absorption of food. It is associated with relatively poor outcomes, including reduced quality of life and survival.1 Common causes are cancer of the head/body of the pancreas, chronic pancreatitis, pancreatic resection and cystic fibrosis. It can occur following duodenectomy, gastrectomy or untreated coeliac disease via a reduction in cholecystokinin and thereby post-prandial pancreatic stimulation.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Source Type: research
Authors: Dietrich CF, Hollerweger A, Dirks K, Higginson A, Serra C, Calabrese E, Dong Y, Hausken T, Maconi G, Mihmanli I, Nürnberg D, Nylund K, Pallotta N, Ripollés T, Romanini L, Săftoiu A, Sporea I, Wüstner M, Maaser C, Gilja OH Abstract Transabdominal gastrointestinal ultrasound (GIUS) is unique in its capacity to examine the bowel non-invasively and in its physiological condition, including extra-intestinal features such as the splanchnic vessels, mesentery, omentum and lymph nodes- even at the bedside. Despite this, and its extensive documentation for its usefulness, it has only been fully im...
Source: Medical Ultrasonography - Category: Radiology Tags: Med Ultrason Source Type: research
We present an extremely rare case of a 3-year-old child with a primary carcinoid tumor of the prostate. A 3-year-old boy presented with failure to thrive, constipation, recurrent respiratory tract infections, and pain in the genital area. His karyotype was normal and cystic fibrosis and coeliac disease were excluded prior to further investigation. An abdominopelvic computed tomography scan revealed a prostatic mass. Transrectal ultrasound-guided prostate biopsy was therefore performed and pathological examination revealed a carcinoid tumor.
Source: Urology - Category: Urology & Nephrology Authors: Tags: Pediatric Case Reports Source Type: research
We present an extremely rare case of a 3-year-old child with a primary carcinoid tumour of the prostate. A 3-year-old boy presented with failure to thrive, constipation, recurrent respiratory tract infections and pain in the genital area. His karyotype was normal and cystic fibrosis and coeliac disease were excluded prior to further investigation. An abdominopelvic CT scan revealed a prostatic mass. Transrectal ultrasound-guided prostate biopsy was therefore performed and pathological examination revealed a carcinoid tumour.
Source: Urology - Category: Urology & Nephrology Authors: Source Type: research
Authors: Maiuri L, Raia V, Piacentini M, Tosco A, Villella VR, Kroemer G Abstract Cystic Fibrosis (CF) is the most frequent lethal monogenetic disease affecting humans. CF is characterized by mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel whose malfunction triggers the activation of transglutaminase-2 (TGM2), as well as the inactivation of the Beclin-1 (BECN1) complex resulting in disabled autophagy. CFTR inhibition, TGM2 activation and BECN1 sequestration engage in an 'infernal trio' that locks the cell in a pro-inflammatory state through anti-homeostatic feedforward lo...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Abstract In celiac disease (CD), an intolerance to dietary gluten/gliadin, antigenic gliadin peptides trigger an HLA-DQ2/DQ8-restricted adaptive Th1 immune response. Epithelial stress, induced by other non-antigenic gliadin peptides, is required for gliadin to become fully immunogenic. We found that cystic-fibrosis-transmembrane-conductance-regulator (CFTR) acts as membrane receptor for gliadin-derived peptide P31-43, as it binds to CFTR and impairs its channel function. P31-43-induced CFTR malfunction generates epithelial stress and intestinal inflammation. Maintaining CFTR in an active open conformation by the C...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Objectives: Pancreatic insufficiency in children is usually associated with diseases such as cystic fibrosis, Shwachman-Diamond syndrome, or chronic pancreatitis. Fecal elastase-1 is a reliable laboratory test for the diagnosis of exocrine pancreatic insufficiency (EPI). Transient pancreatic insufficiency has been rarely described and data on this entity are lacking in the medical literature. In this retrospective study we report 17 cases of transient pancreatic insufficiency presented mainly with failure to thrive and/or diarrhea. Methods: We followed 43 children (age range 1 month–18 years) with low fecal elas...
Source: Journal of Pediatric Gastroenterology and Nutrition - Category: Gastroenterology Tags: Original Articles: Pancreatology Source Type: research
Intestinal handling of dietary proteins usually prevents local inflammatory and immune responses and promotes oral tolerance. However, in ~ 1% of the world population, gluten proteins from wheat and related cereals trigger an HLA DQ2/8-restricted TH1 immune and antibody response leading to celiac disease. Prior epithelial stress and innate immune activation are essential for breaking oral tolerance to the gluten component gliadin. How gliadin subverts host intestinal mucosal defenses remains elusive. Here, we show that the α-gliadin-derived LGQQQPFPPQQPY peptide (P31–43) inhibits the function of cystic&nbs...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Immunology, Membrane & Intracellular Transport, Molecular Biology of Disease Articles Source Type: research
Coeliac disease (CD) is an inflammatory autoimmune disease caused by ingestion of gluten proteins, mainly gliadin. Undigested gliadin proline-rich peptides trigger the innate and adaptive immune response, resulting in intestinal cell stress and damage. A new study by Villella et al (2019) addressing the unclear primary cause of intestinal cell stress reports that gliadin peptides inhibit the function of the chloride and bicarbonate channel CFTR, causing intestinal cell stress, which is sufficient to trigger CD symptoms. Notably, CFTR potentiators used to treat cystic fibrosis effectively rescue CFTR function and marke...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Immunology, Membrane & Intracellular Transport, Molecular Biology of Disease News [amp ] Views Source Type: research
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