scholarly journals Immunoglobulin A Mucosal Immunity and Altered Respiratory Epithelium in Cystic Fibrosis

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3603
Author(s):  
Sophie Gohy ◽  
Alexandra Moeremans ◽  
Charles Pilette ◽  
Amandine Collin
Keyword(s):  
Cystic Fibrosis ◽  
Mucociliary Clearance ◽  
Current Knowledge ◽  
Immunoglobulin A ◽  
Bacterial Overgrowth ◽  
Respiratory Epithelium ◽  
Physical Barrier ◽  
Local Immunity ◽  
Cftr Protein ◽  
Protein Dysfunction

The respiratory epithelium represents the first chemical, immune, and physical barrier against inhaled noxious materials, particularly pathogens in cystic fibrosis. Local mucus thickening, altered mucociliary clearance, and reduced pH due to CFTR protein dysfunction favor bacterial overgrowth and excessive inflammation. We aimed in this review to summarize respiratory mucosal alterations within the epithelium and current knowledge on local immunity linked to immunoglobulin A in patients with cystic fibrosis.

Cystic Fibrosis: Pathophysiology of Lung Disease

2019 ◽  
Vol 40 (06) ◽  
pp. 715-726 ◽  
Author(s):  
Christelle Bergeron ◽  
André M. Cantin
Keyword(s):  
Cystic Fibrosis ◽  
Mucociliary Clearance ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Cftr Gene ◽  
Susceptibility To Infection ◽  
Life Threatening ◽  
Cftr Protein ◽  
And Function

AbstractCystic fibrosis (CF) is a common, life-threatening, multisystemic, autosomal recessive disorder. In the last few years, giant steps have been made with regard to the understanding of CF pathophysiology, allowing the scientific community to propose mechanisms that cause the myriad of CF clinical manifestations. Following the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989, the structure and function of the CFTR protein were described. Since then, more than 2,000 variants of the CFTR gene and their impact on the amount and function of the CFTR protein have been reported. The role of the CFTR protein as an ion channel transporting chloride and bicarbonate and its repercussions on different epithelial cell-lined organs and mucus are now better understood. Mechanisms behind susceptibility to infection in CF have also been proposed and include abnormalities in the composition, volume and acidity of the airway surface liquid, changes in the submucosal gland's anatomy and function, and deficiencies in the mucociliary clearance system. Numerous hypotheses explaining the excessive inflammatory response in CF are also debated and involve impaired mucociliary clearance, persistent hypoxia, lipid abnormalities, protease and antiprotease disproportion, and oxidant and antioxidant imbalance. The purpose of this review is to summarize our current knowledge of CF pathophysiology, including significant historic discoveries and most recent breakthroughs, and to improve understanding and awareness of this fatal disease.

The effect of probiotics on the level of immunoglobulin A in women with violation of the biocenosis of the vagina

2017 ◽  
pp. 85-88
Author(s):  
O.I. Ostapenko ◽  
◽  
V.P. Kvashenko ◽  
I.K. Akimova ◽  
I.N. Nosova ◽  
...  
Keyword(s):  
Immunoglobulin A ◽  
Lactobacillus Rhamnosus ◽  
Test System ◽  
Main Group ◽  
Reproductive Age ◽  
Local Action ◽  
Serum Immunoglobulin ◽  
Control Group ◽  
Local Immunity ◽  
Serum Iga

The objective: the study of immunomodulatory effects of a probiotic, which contains lyophilized Lactobacillus (Lactobacillus rhamnosus) – 13 mg (2,0ґ109 CFU) and lyophilized bifidobacteria (Bifidobacterium lactis) – 4 mg (2,0ґ109 CFU) the level of serum immunoglobulin IgA as a marker of local immunity in the plasma of women of reproductive age with the violation of the biocenosis of the vagina. Patients and methods. The study involved 86 patients of reproductive age with the violation of the vaginal biocenosis, which were divided into two groups according to received treatment. A survey was conducted for all patients in both groups: determine the level of serum IgA, measuring pH of vaginal environment and the quantification of lactobacilli and pathogenic flora with the help of test-system «Florotsenoz» before treatment and in 6 weeks after treatment. The state of vaginal microbiocenosis in both groups before treatment was homogeneous. Patients in both groups as therapy at the first stage of treatment received, if necessary antimicrobial therapy depending on the selected flora. In the second stage (restoration of microflora) patient of the main group received systemic probiotic combined with a complex prebiotic local action, patients in the control group, the probiotic localy in the form of the vaginal candles or tablets. Results. The research stated the increasing level of serum IgA in blood plasma of patients of the main group compared to control group at 20%, normalizing the pH of the vaginal environment in the main group in 94% of cases, which indicates an increase of immunity in mucosal. Conclusion. The inclusion of the systemic probiotic in the scheme of treatment of disorders of biocenosis of the vagina system enhances the increasing of immunity of the mucous membranes, and the vaginal tablets prebiotic of local action restores the own normal microflora of the vagina. Key words: serum immunoglobulin A, local immunity, vaginal dysbiosis, probiotics, prebiotics, vaginal microbiocenosis, the pH of the vaginal environment.

PRO–CF–MED, Clinical Proof of concept for a RNA–targeting Oligonucleotide for a Cystic fibrosis–F508del MEDication, Horizon2020

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 52-54
Author(s):  
Nicolas Lamontagne
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Rna Targeting ◽  
Threatening Condition ◽  
Life Threatening ◽  
Cftr Protein ◽  
Disease Modifying ◽  
Cystic Fibrosis Transmembrane ◽  
Specific Challenge

Cystic fibrosis (CF) is a progressive life–shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leading to a dysfunctional CFTR protein. The disease affects over 70,000 patients worldwide and while many mutations are known, the F508del mutation affects 90% of all patients. The absence of CFTR in the plasma membrane leads to a dramatic decrease in chloride efflux, resulting in viscous mucus that causes severe symptoms in vital organs like the lungs and intestines. For CF patients that suffer from the life threatening F508del mutation only palliative treatment exist. PRO–CF–MED addresses the specific challenge of this call by introducing the first disease modifying medication for the treatment of the CF patients with F508del mutation. The PRO–CF–MED project has been designed to assess the potential clinical efficacy of QR–010, an innovative disease modifying oligonucleotide–based treatment for F508del patients. Partners within PRO–CF–MED have generated very promising preclinical evidence for QR–010 which allows for further clinical assessment of QR–010 in clinical trials. PRO–CF–MED will enable the fast translation of QR–010 towards clinical practice and market authorisation. PRO–CF–MED has the potential to transform this life–threatening condition into a manageable one.

scholarly journals The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Saeedeh Talebi ◽  
Mahammad Safarian ◽  
Mahmood Reza Jaafari ◽  
Seyed Javad Sayedi ◽  
Zahra Abbasi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Controlled Trial ◽  
Genetic Disorder ◽  
The Body ◽  
Inflammatory Factors ◽  
Secondary Outcome ◽  
Nasopharyngeal Swab ◽  
Nutritional Strategy ◽  
Cftr Protein ◽  
The Impact

Abstract Background Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. Methods This prospective, double blind control trial will be conducted at the Akbar Children’s Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. Discussion Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. Trial registration Iranian Registry of Clinical Trials IRCT20200705048018N1. Registered on July 10, 2020.

scholarly journals The Multifaceted Roles of MicroRNAs in Cystic Fibrosis

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1102
Author(s):  
Fatima Domenica Elisa De Palma ◽  
Valeria Raia ◽  
Guido Kroemer ◽  
Maria Chiara Maiuri
Keyword(s):  
Cystic Fibrosis ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Pancreatic Insufficiency ◽  
Clinical Manifestations ◽  
Predictive Biomarkers ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Multisystemic Disease

Cystic fibrosis (CF) is a lifelong disorder affecting 1 in 3500 live births worldwide. It is a monogenetic autosomal recessive disease caused by loss-of-function mutations in the gene encoding the chloride channel cystic fibrosis transmembrane conductance regulator (CFTR), the impairment of which leads to ionic disequilibria in exocrine organs. This translates into a chronic multisystemic disease characterized by airway obstruction, respiratory infections, and pancreatic insufficiency as well as hepatobiliary and gastrointestinal dysfunction. Molecular characterization of the mutational heterogeneity of CFTR (affected by more than 2000 variants) improved the understanding and management of CF. However, these CFTR variants are linked to different clinical manifestations and phenotypes, and they affect response to treatments. Expanding evidence suggests that multisystemic disease affects CF pathology via impairing either CFTR or proteins regulated by CFTR. Thus, altering the expression of miRNAs in vivo could constitute an appealing strategy for developing new CF therapies. In this review, we will first describe the pathophysiology and clinical management of CF. Then, we will summarize the current knowledge on altered miRNAs in CF patients, with a focus on the miRNAs involved in the deregulation of CFTR and in the modulation of inflammation. We will highlight recent findings on the potential utility of measuring circulating miRNAs in CF as diagnostic, prognostic, and predictive biomarkers. Finally, we will provide an overview on potential miRNA-based therapeutic approaches.

scholarly journals Structure and Function of the CFTR Chloride Channel

1999 ◽  
Vol 79 (1) ◽  
pp. S23-S45 ◽  
Author(s):  
DAVID N. SHEPPARD ◽  
MICHAEL J. WELSH
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channel ◽  
Atp Hydrolysis ◽  
Current Knowledge ◽  
Structure And Function ◽  
Binding Domains ◽  
Transporter Family ◽  
Membrane Spanning ◽  
And Function ◽  
R Domain

Sheppard, David N., and Michael J. Welsh. Structure and Function of the CFTR Chloride Channel. Physiol. Rev. 79 , Suppl.: S23–S45, 1999. — The cystic fibrosis transmembrane conductance regulator (CFTR) is a unique member of the ABC transporter family that forms a novel Cl− channel. It is located predominantly in the apical membrane of epithelia where it mediates transepithelial salt and liquid movement. Dysfunction of CFTR causes the genetic disease cystic fibrosis. The CFTR is composed of five domains: two membrane-spanning domains (MSDs), two nucleotide-binding domains (NBDs), and a regulatory (R) domain. Here we review the structure and function of this unique channel, with a focus on how the various domains contribute to channel function. The MSDs form the channel pore, phosphorylation of the R domain determines channel activity, and ATP hydrolysis by the NBDs controls channel gating. Current knowledge of CFTR structure and function may help us understand better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.

scholarly journals Influence of the Surfactant Tyloxapol on Mucociliary Clearance in Human Respiratory Cystic Fibrosis Cells

Pharmacology ◽  
2016 ◽  
Vol 98 (1-2) ◽  
pp. 1-3
Author(s):  
Eckhard Beubler ◽  
Rainald Fischer ◽  
Gerald Untersteiner ◽  
Wolfgang Strohmaier
Keyword(s):  
Cystic Fibrosis ◽  
Mucociliary Clearance

Application of the Glucose Hydrogen Breath Test for the Detection of Bacterial Overgrowth in Patients with Cystic Fibrosis––A Reliable Method?

2008 ◽  
Vol 54 (8) ◽  
pp. 1730-1735 ◽  
Author(s):  
Arne R. J. Schneider ◽  
Stefanie Klueber ◽  
Hans-Georg Posselt ◽  
Benjamin Funk ◽  
Lydia Murzynski ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Breath Test ◽  
Reliable Method ◽  
Bacterial Overgrowth ◽  
Hydrogen Breath Test

scholarly journals Characterization of Wild-Type and ΔF508 Cystic Fibrosis Transmembrane Regulator in Human Respiratory Epithelia

2005 ◽  
Vol 16 (5) ◽  
pp. 2154-2167 ◽  
Author(s):  
Silvia M. Kreda ◽  
Marcus Mall ◽  
April Mengos ◽  
Lori Rochelle ◽  
James Yankaskas ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Normal Subjects ◽  
Cell Types ◽  
Cystic Fibrosis Transmembrane Regulator ◽  
Ciliated Cells ◽  
Metabolic Fate ◽  
Specific Expression ◽  
Δf508 Cftr ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane

Previous studies in native tissues have produced conflicting data on the localization and metabolic fate of WT and ΔF508 cystic fibrosis transmembrane regulator (CFTR) in the lung. Combining immunocytochemical and biochemical studies utilizing new high-affinity CFTR mAbs with ion transport assays, we examined both 1) the cell type and region specific expression of CFTR in normal airways and 2) the metabolic fate of ΔF508 CFTR and associated ERM proteins in the cystic fibrosis lung. Studies of lungs from a large number of normal subjects revealed that WT CFTR protein localized to the apical membrane of ciliated cells within the superficial epithelium and gland ducts. In contrast, other cell types in the superficial, gland acinar, and alveolar epithelia expressed little WT CFTR protein. No ΔF508 CFTR mature protein or function could be detected in airway specimens freshly excised from a large number of ΔF508 homozygous subjects, despite an intact ERM complex. In sum, our data demonstrate that WT CFTR is predominantly expressed in ciliated cells, and ΔF508 CFTR pathogenesis in native tissues, like heterologous cells, reflects loss of normal protein processing.

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