Cystic fibrosis is a risk factor for celiac disease.

Walkowiak, Jarosław; Blask-Osipa, Anna; Lisowska, Aleksandra; Oralewska, Beata; Pogorzelski, Andrzej; Cichy, Wojciech; Sapiejka, Ewa; Kowalska, Mirosława; Korzon, Michał; Szaflarska-Popławska, Anna

doi:10.18388/abp.2010_2382

Cited by 43 publications

(51 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HLA-DQA1 and HLA-DQB1 are likely genetic markers of the Celiac Disease [71] which was suggested to be a risk factor in CF [72, 73]. Therefore, together with our present results, we propose HLA-DQA1 and HLA-DQB1 genes, as new modifiers in CF.…”

Section: Resultssupporting

confidence: 79%

In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis

2017

View full text Add to dashboard Cite

Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

show abstract

Section: Resultssupporting

confidence: 79%

In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis

2017

View full text Add to dashboard Cite

show abstract

“…An approximately threefold increase in the prevalence of fully diagnosed CD, as well as a ~ 4% prevalence of positive anti‐TG2‐IgA autoantibodies, a serological marker of CD, even in the absence of villous atrophy (Lionetti et al , ), has been reported in several cohorts of patients with cystic fibrosis (CF; Fluge et al , ; Walkowiak et al , ; De Lisle & Borowitz, ), including ours (Appendix Table S1). CF is the most frequent monogenic lethal disease worldwide (Cutting, ) , caused by loss‐of‐function mutations of the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic adenosine monophosphate (cAMP)‐regulated anion channel that mediates chloride/bicarbonate transport across epithelia (Gadsby et al , ; Cutting, ).…”

Section: Introductionsupporting

confidence: 57%

A pathogenic role for cystic fibrosis transmembrane conductance regulator in celiac disease

Villella¹,

et al. 2018

View full text Add to dashboard Cite

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 fibrosis transmembrane conductance regulator (CFTR), an anion channel pivotal for epithelial adaptation to cell‐autonomous or environmental stress. P31–43 binds to, and reduces ATPase activity of, the nucleotide‐binding domain‐1 (NBD1) of CFTR, thus impairing CFTR function. This generates epithelial stress, tissue transglutaminase and inflammasome activation, NF‐κB nuclear translocation and IL‐15 production, that all can be prevented by potentiators of CFTR channel gating. The CFTR potentiator VX‐770 attenuates gliadin‐induced inflammation and promotes a tolerogenic response in gluten‐sensitive mice and cells from celiac patients. Our results unveil a primordial role for CFTR as a central hub orchestrating gliadin activities and identify a novel therapeutic option for celiac disease.

show abstract

“…The authors postulated that intestinal inflammation, exocrine pancreatic insufficiency leading to protein exposure, and a shorter time of breast feeding may predispose genetically CF patients to celiac disease. 10 Indeed, children with CF have increased intestinal inflammatory markers, including eosinophilic cationic protein and neutrophil elastase. 11 Evidence also suggests that complementary food avoidance before 4 months of age allows breast milk to provide immunologic protection from celiac disease in genetically at-risk individuals.…”

Section: Discussionmentioning

confidence: 99%