Publications
Below you can find a list of our published research.
Below you can find a list of our published research.
195 results
American journal of respiratory and critical care medicine, 27 4 2024 High-Dimensional Mass Cytometry Reveals Emphysema-associated Changes in the Pulmonary Immune System. Jia L, Li N, Abdelaal TRM, Guo N, IJsselstein ME, van Unen V, Lindelauf C, Jiang Q, Xiao Y, Pascutti MF, Hiemstra PS, Koning F, Stolk J, Khedoe PPSJ
Rationale: Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood. Objective: To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema. Methods: We used single-cell mass cytometry to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 controls. Imaging mass cytometry (IMC) was applied to id... Abstract
American journal of respiratory cell and molecular biology, Volume 70, Issue 2, 1 1 2024, Pages 149-152 Loss of Pulmonary Endothelial Cells in Emphysema Impairs Support of Human Alveolar Epithelial Cell Growth. Ravi A, Jia L, Wu X, van der Meer AD, Gosens R, Stolk J, van der Does AM, Koning F, Hiemstra PS, Khedoe PPJS
The New England journal of medicine, Volume 390, Issue 4, 1 1 2024, Pages 387 Liver Transplantation. Kappe NN, Stolk J, van Hoek B
COPD, Volume 20, Issue 1, 1 1 2023, Pages 292-297 Governmental Non-Pharmaceutical Interventions during the COVID-19 Pandemic and the COPD Exacerbation and Respiratory Infection Rate in Patients with Alpha-1 Antitrypsin Deficiency. Kappe NN, Alagem N, Tov N, Stolk J
During the COVID-19 pandemic the number of hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations was significantly reduced. The reason for this decline is not fully understood. Governmental non-pharmaceutical interventions (NPI's), an increase in community treated exacerbations, or healthcare avoidance by patients, are potential reasons. For the current study, the impact of Dutch governmental NPI's on the COPD exacerbations and respiratory infections rat... Abstract
Frontiers in cell and developmental biology, Volume 11, 19 3 2023, Pages 1165581 Cigarette smoke restricts the ability of mesenchymal cells to support lung epithelial organoid formation. Khedoe PPSJ, van Schadewijk WAAM, Schwiening M, Ng-Blichtfeldt JP, Marciniak SJ, Stolk J, Gosens R, Hiemstra PS
Adequate lung epithelial repair relies on supportive interactions within the epithelial niche, including interactions with WNT-responsive fibroblasts. In fibroblasts from patients with chronic obstructive pulmonary disease (COPD) or upon in vitro cigarette smoke exposure, Wnt/β-catenin signalling is distorted, which may affect interactions between epithelial cells and fibroblasts resulting in inadequate lung repair. We hypothesized that cigarette smoke (CS), the main risk factor for COPD, interf... Abstract
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
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
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 6 times since 2022 (4.4 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 3 times since 2022 (1.4 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 15 times since 2022 (6.8 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 (0.4 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 2 times since 2021 (0.7 per year) source: EuropePMC
ERJ open research, Volume 7, Issue 3, 1 1 2021, Pages 194-2021 Long-term effect of α<sub>1</sub>-antitrypsin augmentation therapy on the decline of FEV<sub>1</sub> 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
Background: 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). Methods: 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 e... Abstract
Cited 4 times since 2021 (1.4 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 2 times since 2021 (0.6 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 (0.6 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 2 times since 2020 (0.5 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 28 times since 2020 (7.3 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 10 times since 2020 (2.5 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