190 results
The European respiratory journal,
Volume 61, Issue 3, 30 5 2023, Pages 2201949
Characteristics of individuals with alpha-1 antitrypsin deficiency from Northern and Southern European countries: EARCO international registry.
Miravitlles M, Turner AM, Torres-Duran M, Tanash H, Rodríguez-García C, López-Campos JL, Chlumsky J, Guimaraes C, Rodríguez-Hermosa JL, Corsico A, Martinez-González C, Hernández-Pérez JM, Bustamante A, Parr DG, Casas-Maldonado F, Hecimovic A, Janssens W, Lara B, Barrecheguren M, González C, Stolk J, Esquinas C, Clarenbach CF, EARCO study investigators
Abstract
Respiratory research,
Volume 24, Issue 1, 18 3 2023, Pages 57
Correction: Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.
Miravitlles M, Turner AM, Torres-Duran M, Tanash H, Rodríguez-García C, López-Campos JL, Chlumsky J, Guimaraes C, Rodríguez-Hermosa JL, Corsico A, Martinez-González C, Hernández-Pérez JM, Bustamante A, Parr DG, Casas-Maldonado F, Hecimovic A, Janssens W, Lara B, Barrecheguren M, González C, Stolk J, Esquinas C, Clarenbach CF
Abstract
International journal of molecular sciences,
Volume 24, Issue 3, 27 4 2023, Pages 2485
Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.
Kamp JC, Kappe NN, Moro CF, Fuge J, Kuehnel MP, Wrenger S, Welte T, Hoek BV, Jonigk DD, Khedoe PPSJ, Strnad P, Björnstedt M, Stolk J, Janciauskiene S, Nemeth A
PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses. Liver biopsies obtained during 1979-2010 at the Department of Paediatrics, Ka...
Abstract
Cited 1 times since 2022 (2.2 per year)
source: EuropePMC
Respiratory research,
Volume 23, Issue 1, 16 3 2022, Pages 352
Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry.
Miravitlles M, Turner AM, Torres-Duran M, Tanash H, Rodríguez-García C, López-Campos JL, Chlumsky J, Guimaraes C, Rodríguez-Hermosa JL, Corsico A, Martinez-González C, Hernández-Pérez JM, Bustamante A, Parr DG, Casas-Maldonado F, Hecimovic A, Janssens W, Lara B, Barrecheguren M, González C, Stolk J, Esquinas C, Clarenbach CF
Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels 1000 individuals with AATD from 15 cou...
Abstract
Cellular and molecular life sciences : CMLS,
Volume 79, Issue 9, 1 1 2022, Pages 503
Keratin 8 is a scaffolding and regulatory protein of ERAD complexes.
Pranke IM, Chevalier B, Premchandar A, Baatallah N, Tomaszewski KF, Bitam S, Tondelier D, Golec A, Stolk J, Lukacs GL, Hiemstra PS, Dadlez M, Lomas DA, Irving JA, Delaunay-Moisan A, van Anken E, Hinzpeter A, Sermet-Gaudelus I, Edelman A
Early recognition and enhanced degradation of misfolded proteins by the endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) cause defective protein secretion and membrane targeting, as exemplified for Z-alpha-1-antitrypsin (Z-A1AT), responsible for alpha-1-antitrypsin deficiency (A1ATD) and F508del-CFTR (cystic fibrosis transmembrane conductance regulator) responsible for cystic fibrosis (CF). Prompted by our previous observation that decreasing Keratin 8 (K8) express...
Abstract
Cited 2 times since 2022 (1.6 per year)
source: EuropePMC
Biomolecules,
Volume 12, Issue 3, 28 4 2022, Pages 380
The Relationship between Plasma Alpha-1-Antitrypsin Polymers and Lung or Liver Function in ZZ Alpha-1-Antitrypsin-Deficient Patients.
Sark AD, Fromme M, Olejnicka B, Welte T, Strnad P, Janciauskiene S, Stolk J
Alpha-1-Antitrypsin (AAT) is a protein of the SERPINA1 gene. A single amino acid mutation (Lys342Glu) results in an expression of misfolded Z-AAT protein, which has a high propensity to intra- and extra-cellular polymerization. Here, we asked whether levels of circulating Z-AAT polymers are associated with the severity of lung disease, liver disease, or both. We obtained cross sectional data from the Dutch part of the Alpha1 International Registry of 52 ZZ-AAT patients who performed a pulmonary...
Abstract
Cited 5 times since 2022 (3.8 per year)
source: EuropePMC
American journal of physiology. Lung cellular and molecular physiology,
Volume 322, Issue 4, 9 2 2022, Pages L526-L538
Organoid-based expansion of patient-derived primary alveolar type 2 cells for establishment of alveolus epithelial Lung-Chip cultures.
van Riet S, van Schadewijk A, Khedoe PPSJ, Limpens RWAL, Bárcena M, Stolk J, Hiemstra PS, van der Does AM
Development of effective treatment strategies for lung tissue destruction as seen in emphysema would greatly benefit from representative human in vitro models of the alveolar compartment. Studying how cellular cross talk and/or (altered) biomechanical cues affect alveolar epithelial function could provide new insight for tissue repair strategies. Preclinical models of the alveolus ideally combine human primary patient-derived lung cells with advanced cell culture applications such as breathing-r...
Abstract
Cited 1 times since 2021 (0.5 per year)
source: EuropePMC
International journal of molecular sciences,
Volume 22, Issue 15, 27 4 2021, Pages 8031
The Course of AαVal541 as a Proteinase 3 Specific Neo-Epitope after Alpha-1-Antitrypsin Augmentation in Severe Deficient Patients.
Schouten IGM, Mumford RA, Moes DJAR, Hiemstra PS, Stolk J
In alpha-1-antitrypsin deficiency (AATD), neutrophil serine proteases such as elastase and proteinase 3 (PR3) are insufficiently inhibited. A previous study in AATD patients showed a higher plasma level of the specific PR3-generated fibrinogen-derived peptide AαVal541, compared with healthy controls. Here, we analyzed the course of AαVal541 plasma levels during 4 weeks after a single iv dose of 240 mg/kg AAT in ten patients with genotype Z/Rare or Rare/Rare. To this end, we developed an immunoas...
Abstract
Cited 1 times since 2021 (0.5 per year)
source: EuropePMC
ERJ open research,
Volume 7, Issue 3, 1 1 2021, Pages 194-2021
Long-term effect of α1-antitrypsin augmentation therapy on the decline of FEV1 in deficient patients: an analysis of the AIR database.
Schouten IGM, Kasteleyn MJ, Tsonaka R, Bals R, Turner AC, Ferrarotti I, Corsico AG, Lara B, Miravitlles M, Stockley RA, Stolk J
Patients with ZZ (Glu342Lys) α-1-antitrypsin deficiency (ZZ-AATD) who received augmentation therapy with α-1-antitrypsin (AAT) in randomised controlled trials over 2-3 years failed to show a significant reduction of the annual decline of forced expiratory volume in 1 s (FEV1). To compare the trajectory of FEV1 change during 4 or more years in ZZ-AATD patients with emphysema receiving or not receiving intravenous augmentation therapy, a retrospective analysis of FEV1 values entered in the Alpha-1...
Abstract
Cited 3 times since 2021 (1.5 per year)
source: EuropePMC
eLife,
Volume 10, 18 3 2021, Pages e64881
Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs.
Tumpara S, Ballmaier M, Wrenger S, König M, Lehmann M, Lichtinghagen R, Martinez-Delgado B, Korenbaum E, DeLuca D, Jedicke N, Welte T, Fromme M, Strnad P, Stolk J, Janciauskiene S
Expression levels of CX3CR1 (C-X3-C motif chemokine receptor 1) on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host's misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, a novel example...
Abstract
Cited 1 times since 2021 (0.4 per year)
source: EuropePMC
International journal of molecular sciences,
Volume 22, Issue 3, 21 3 2021, Pages 1065
Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches.
Viglio S, Bak EG, Schouten IGM, Iadarola P, Stolk J
As a known genetic cause of chronic obstructive pulmonary disease (COPD), alpha1-antitrypsin deficiency (AATD) can cause severe respiratory problems at a relatively young age. These problems are caused by decreased or absent levels of alpha1-antitrypsin (AAT), an antiprotease which is primarily functional in the respiratory system. If the levels of AAT fall below the protective threshold of 11 µM, the neutrophil-derived serine proteases neutrophil elastase (NE) and proteinase 3 (PR3), which are...
Abstract
Cited 2 times since 2020 (0.8 per year)
source: EuropePMC
ERJ open research,
Volume 6, Issue 4, 26 4 2020, Pages 157-2020
Prediction of lung function and lung density of young adults who had bronchopulmonary dysplasia.
Santema HY, Stolk J, Los M, Stoel BC, Tsonaka R, Merth IT
COPD risk is jointly determined by fetal lung development, lung growth rate and lung growth duration leading to the maximally attained level of lung function in early adulthood. Bronchopulmonary dysplasia (BPD) is considered a developmental arrest of alveolarisation. Long-term outcome studies of adult survivors born before the introduction of surfactant therapy ("old BPD") showed impaired lung function. We aimed to predict adult lung function and lung density in a cohort of premature i...
Abstract
Cited 1 times since 2020 (0.4 per year)
source: EuropePMC
Molecules (Basel, Switzerland),
Volume 25, Issue 17, 2 1 2020, Pages E4014
Methods of Purification and Application Procedures of Alpha1 Antitrypsin: A Long-Lasting History.
Viglio S, Iadarola P, D'Amato M, Stolk J
The aim of the present report is to review the literature addressing the methods developed for the purification of alpha1-antitrypsin (AAT) from the 1950s to the present. AAT is a glycoprotein whose main function is to protect tissues from human neutrophil elastase (HNE) and other proteases released by neutrophils during an inflammatory state. The lack of this inhibitor in human serum is responsible for the onset of alpha1-antitrypsin deficiency (AATD), which is a severe genetic disorder that af...
Abstract
Cited 17 times since 2020 (5.8 per year)
source: EuropePMC
Stem cells (Dayton, Ohio),
Volume 38, Issue 11, 18 3 2020, Pages 1467-1478
Wnt/β-catenin signaling is critical for regenerative potential of distal lung epithelial progenitor cells in homeostasis and emphysema.
Hu Y, Ng-Blichfeldt JP, Ota C, Ciminieri C, Ren W, Hiemstra PS, Stolk J, Gosens R, Königshoff M
Wnt/β-catenin signaling regulates progenitor cell fate decisions during lung development and in various adult tissues. Ectopic activation of Wnt/β-catenin signaling promotes tissue repair in emphysema, a devastating lung disease with progressive loss of parenchymal lung tissue. The identity of Wnt/β-catenin responsive progenitor cells and the potential impact of Wnt/β-catenin signaling on adult distal lung epithelial progenitor cell function in emphysema are poorly understood. Here, we used TCF/...
Abstract
Cited 8 times since 2020 (2.6 per year)
source: EuropePMC
Journal of innate immunity,
Volume 12, Issue 5, 14 2 2020, Pages 410-421
Modulation of Airway Epithelial Innate Immunity and Wound Repair by M(GM-CSF) and M(M-CSF) Macrophages.
van Riet S, van Schadewijk A, de Vos S, Vandeghinste N, Rottier RJ, Stolk J, Hiemstra PS, Khedoe P
Airway epithelial cells and macrophages participate in inflammatory responses to external noxious stimuli, which can cause epithelial injury. Upon injury, epithelial cells and macrophages act in concert to ensure rapid restoration of epithelial integrity. The nature of the interactions between these cell types during epithelial repair is incompletely understood. We used an in vitro human coculture model of primary bronchial epithelial cells cultured at the air-liquid interface (ALI-PBEC) and pol...
Abstract
Cited 7 times since 2020 (2 per year)
source: EuropePMC
ERJ open research,
Volume 6, Issue 1, 1 1 2020, Pages 181-2019
Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency.
Greulich T, Altraja A, Barrecheguren M, Bals R, Chlumsky J, Chorostowska-Wynimko J, Clarenbach C, Corda L, Corsico AG, Ferrarotti I, Esquinas C, Gouder C, Hećimović A, Ilic A, Ivanov Y, Janciauskiene S, Janssens W, Kohler M, Krams A, Lara B, Mahadeva R, McElvaney G, Mornex JF, O'Hara K, Parr D, Piitulainen E, Schmid-Scherzer K, Seersholm N, Stockley RA, Stolk J, Sucena M, Tanash H, Turner A, Ulmeanu R, Wilkens M, Yorgancioğlu A, Zaharie A, Miravitlles M
Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of...
Abstract
Cited 17 times since 2019 (4.8 per year)
source: EuropePMC
The European respiratory journal,
Volume 54, Issue 5, 21 3 2019, Pages 1900673
Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD.
Stolk J, Tov N, Chapman KR, Fernandez P, MacNee W, Hopkinson NS, Piitulainen E, Seersholm N, Vogelmeier CF, Bals R, McElvaney G, Stockley RA
Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment.We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation...
Abstract
Cited 2 times since 2019 (0.6 per year)
source: EuropePMC
Journal of thoracic imaging,
Volume 34, Issue 6, 1 1 2019, Pages 373-379
Pulmonary Vascular Morphology Associated With Gas Exchange in Systemic Sclerosis Without Lung Fibrosis.
Zhai Z, Staring M, Ninaber MK, Vries-Bouwstra JK, Schouffoer AA, Kroft LJ, Stolk J, Stoel BC
PURPOSE:Gas exchange in systemic sclerosis (SSc) is known to be affected by fibrotic changes in the pulmonary parenchyma. However, SSc patients without detectable fibrosis can still have impaired gas transfer. We aim to investigate whether pulmonary vascular changes could partly explain a reduction in gas transfer of SSc patients without fibrosis. MATERIALS AND METHODS:We selected 77 patients whose visual computed tomography (CT) scoring showed no fibrosis. Pulmonary vessels were detected automa...
Abstract
Cited 33 times since 2019 (8.2 per year)
source: EuropePMC
Gastroenterology,
Volume 157, Issue 3, 20 3 2019, Pages 705-719.e18
Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.
Hamesch K, Mandorfer M, Pereira VM, Moeller LS, Pons M, Dolman GE, Reichert MC, Schneider CV, Woditsch V, Voss J, Lindhauer C, Fromme M, Spivak I, Guldiken N, Zhou B, Arslanow A, Schaefer B, Zoller H, Aigner E, Reiberger T, Wetzel M, Siegmund B, Simões C, Gaspar R, Maia L, Costa D, Bento-Miranda M, van Helden J, Yagmur E, Bzdok D, Stolk J, Gleiber W, Knipel V, Windisch W, Mahadeva R, Bals R, Koczulla R, Barrecheguren M, Miravitlles M, Janciauskiene S, Stickel F, Lammert F, Liberal R, Genesca J, Griffiths WJ, Trauner M, Krag A, Trautwein C, Strnad P, European Alpha1-Liver Study Group
Background & aims: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form...
Abstract
Cited 23 times since 2019 (5.6 per year)
source: EuropePMC
American journal of physiology. Lung cellular and molecular physiology,
Volume 317, Issue 1, 10 2 2019, Pages L14-L28
TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation.
Ng-Blichfeldt JP, de Jong T, Kortekaas RK, Wu X, Lindner M, Guryev V, Hiemstra PS, Stolk J, Königshoff M, Gosens R
Transforming growth factor-β (TGF-β)-induced fibroblast-to-myofibroblast differentiation contributes to remodeling in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, but whether this impacts the ability of fibroblasts to support lung epithelial repair remains little explored. We pretreated human lung fibroblasts [primary (phFB) or MRC5 cells] with recombinant human TGF-β to induce myofibroblast differentiation, then cocultured them with adult mouse lung epithelial cell a...
Abstract
