scholarly journals Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 765
Author(s):  
Emina Halilbasic ◽  
Elisabeth Fuerst ◽  
Denise Heiden ◽  
Lukasz Japtok ◽  
Susanne C. Diesner ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Lipid Mediator ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Sphingosine 1 Phosphate ◽  
Pathogen Colonization

Recent research has linked sphingolipid (SL) metabolism with cystic fibrosis transmembrane conductance regulator (CFTR) activity, affecting bioactive lipid mediator sphingosine-1-phosphate (S1P). We hypothesize that loss of CFTR function in cystic fibrosis (CF) patients influenced plasma S1P levels. Total and unbound plasma S1P levels were measured in 20 lung-transplanted adult CF patients and 20 healthy controls by mass spectrometry and enzyme-linked immunosorbent assay (ELISA). S1P levels were correlated with CFTR genotype, routine laboratory parameters, lung function and pathogen colonization, and clinical symptoms. Compared to controls, CF patients showed lower unbound plasma S1P, whereas total S1P levels did not differ. A positive correlation of total and unbound S1P levels was found in healthy controls, but not in CF patients. Higher unbound S1P levels were measured in ΔF508-homozygous compared to ΔF508-heterozygous CF patients (p = 0.038), accompanied by higher levels of HDL in ΔF508-heterozygous patients. Gastrointestinal symptoms were more common in ΔF508 heterozygotes compared to ΔF508 homozygotes. This is the first clinical study linking plasma S1P levels with CFTR function and clinical presentation in adult CF patients. Given the emerging role of immunonutrition in CF, our study might pave the way for using S1P as a novel biomarker and nutritional target in CF.

Cystic fibrosis

2011 ◽  
Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Regulator Protein ◽  
Salt And Water Balance ◽  
Cystic Fibrosis Transmembrane

Gastrointestinal manifestations 156Management of gastrointestinal symptoms in children with CF 158Nutrition in CF 158Nutritional management 159Vitamins 160The incidence of cystic fibrosis (CF) is around 1 in 2500. Cases are diagnosed as a consequence of population screening or high-risk screening, or following presentation with clinical symptoms typical of the disorder. The basic defect is in the CFTR (cystic fibrosis transmembrane conductance regulator) protein which codes for a cyclic adenosine monophosphate-regulated chloride transporter in epithelial cells of exocrine organs. This is involved in salt and water balance across epithelial surfaces. The gene is on chromosome 7. There are multiple known mutations, the most common being ...

scholarly journals Sphingosine-1-Phosphate Is a Novel Regulator of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Activity

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0130313 ◽  
Author(s):  
Firhan A. Malik ◽  
Anja Meissner ◽  
Illya Semenkov ◽  
Steven Molinski ◽  
Stan Pasyk ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Sphingosine 1 Phosphate ◽  
Cystic Fibrosis Transmembrane

scholarly journals Predictive value of cystic fibrosis transmembrane conductance regulator (CFTR) in the diagnosis of gastric cancer

2014 ◽  
Vol 37 (4) ◽  
pp. 226 ◽  
Author(s):  
Haiyan Liu ◽  
Wenyong Wu ◽  
Yang Liu ◽  
Changle Zhang ◽  
Zheng Zhou
Keyword(s):  
Gastric Cancer ◽  
Cystic Fibrosis ◽  
Cancer Patients ◽  
Enzyme Linked Immunosorbent Assay ◽  
Transmembrane Conductance Regulator ◽  
Operating Characteristics ◽  
Transmembrane Conductance ◽  
Serum Samples ◽  
Gastric Cancer Patients ◽  
Cystic Fibrosis Transmembrane

Purpose: Gastric cancer is associated with poor prognosis. The high mortality rate of gastric cancer is mainly attributed to late detection, so diagnosis and treatment are crucial to decreasing mortality. The purpose of this study was to examine the predictive accuracy and discriminative ability of cystic fibrosis transmembrane conductance regulator (CFTR) in gastric cancer patients, in addition to the classical cancer tumor biomarkers carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA). Methods: The study was performed on 78 serum samples from gastric cancer patients and 88 serum samples from healthy adults. Serum levels of CFTR, CA199, CEA and CHN were determined by enzyme-linked immunosorbent assay (ELISA) Results: Spearman’s coefficient analysis showed that, in some cases, CFTR was strongly correlated with CA199 and that CFTR levels increased with age. Kruskal-Wallis testing indicated concentrations of CFTR and CA199 had statistically significant association with stage. Logistic regression showed that CFTR and CA199 independently predicted gastric cancer. Receiver operating characteristics (ROC) showed that combinations of CFTR, CA199, and CEA yielded the best ROC curve, with an AUC of 0.875. Conclusions: The results of this study indicate that the serum CFTR has a broad application prospects for detection of GC.

scholarly journals Intestinal current measurement and nasal potential difference to make a diagnosis of cases with inconclusive CFTR genetics and sweat test

2020 ◽  
Vol 7 (1) ◽  
pp. e000736 ◽  
Author(s):  
Rebecca Minso ◽  
Angela Schulz ◽  
Christian Dopfer ◽  
Nadine Alfeis ◽  
Andrea van Barneveld ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Clinical Symptoms ◽  
Potential Difference ◽  
Sweat Test ◽  
Transmembrane Conductance Regulator ◽  
Coding Region ◽  
Transmembrane Conductance ◽  
Related Disorder ◽  
False Positive Diagnosis ◽  
Nasal Potential Difference

BackgroundNasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and CFTR genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).MethodsNPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.ResultsWe assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and CFTR genetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with a CFTR genotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identified CFTR mutation. If two CFTR sequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range.ConclusionThe majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-type CFTR coding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region of CFTR or elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.

scholarly journals Interleukin 8 Secretion from Monocytes of Subjects Heterozygous for the ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation Is Altered

2004 ◽  
Vol 11 (5) ◽  
pp. 819-824 ◽  
Author(s):  
Munir M. Zaman ◽  
Andres Gelrud ◽  
Omer Junaidi ◽  
Meredith M. Regan ◽  
Michel Warny ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Mapk Signaling ◽  
Receptor Expression ◽  
Interleukin 8 ◽  
Healthy Controls ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Surface Receptors ◽  
Cftr Mutations ◽  
Cystic Fibrosis Transmembrane

ABSTRACT Patients with cystic fibrosis (CF) exhibit an excessive host inflammatory response. The aim of this study was to determine (i) whether interleukin 8 (IL-8) secretion is increased from monocytes from subjects heterozygous as well as homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutations and (ii) whether this is due to increased cell surface lipopolysaccharide (LPS) receptors or, alternatively, increased activation of mitogen-activated protein kinases (MAPK). The basal level of IL-8 secretion was higher from monocytes from CF patients than from monocytes from healthy controls (P = 0.02) and obligate heterozygotes (parents of the CF patients). The 50% effective concentrations for LPS-induced IL-8 production for monocytes from both CF patients and obligate heterozygotes were 100-fold lower than those for monocytes from healthy controls (P < 0.05). No differences in the levels of IL-1β production were seen between these groups. Expression of the LPS surface receptors CD14 and Toll-like receptor 4 were not different between CF patients and healthy controls. In contrast, phosphorylation of the MAPKs p38 and ERK occurred at lower doses of LPS in monocytes from patients heterozygous and homozygous for CFTR mutations. These results indicate that a single allelic CFTR mutation is sufficient to augment IL-8 secretion in response to LPS. This is not a result of increased LPS receptor expression but, rather, is associated with alterations in MAPK signaling.

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