- The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry. [Journal Article]Respir Res. 2023 Jan 27; 24(1):34.RR
- CONCLUSIONS: A delayed diagnosis was associated with significantly worse OS and TS. Screening should be improved and efforts to ensure early AATD diagnosis should be intensified.
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- Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function. [Journal Article]
- Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance a…
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- Wilson Disease and Alpha1-Antitrypsin Deficiency: A Review of Non-Invasive Diagnostic Tests. [Review]
- Wilson disease and alpha1-antitrypsin deficiency are two rare genetic diseases that may impact predominantly the liver and/or the brain, and the liver and/or the lung, respectively. The early diagnosis of these diseases is important in order to initiate a specific treatment, when available, ideally before irreversible organ damage, but also to initiate family screening. This review focuses on the…
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- Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db/db Mice. [Journal Article]
- Hypertension may develop before or after the onset of diabetes and it is known to increase the risk of developing diabetic nephropathy. Alpha-1 antitrypsin (AAT) is a multi-functional protein with beneficial effects in various diseases but its role in reducing blood pressure in the diabetic kidney has not been thoroughly studied. Like blood pressure, epithelial sodium channels (ENaC) and its adap…
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- Low-Dose Colchicine Attenuates Sepsis-Induced Liver Injury: A Novel Method for Alleviating Systemic Inflammation. [Journal Article]Inflammation. 2023 Jan 19 [Online ahead of print]I
- Sepsis is a significant public health challenge. The immune system underlies the pathogenesis of the disease. The liver is both an active player and a target organ in sepsis. Targeting the gut immune system using low-dose colchicine is an attractive method for alleviating systemic inflammation in sepsis without inducing immunosuppression. The present study aimed to determine the use of low-dose c…
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- Diagnostic agreement among experts assessing adults presenting with possible cystic fibrosis: need for improvement and implications for patient care. [Journal Article]
- CONCLUSIONS: Our results demonstrate low diagnostic concordance among CF specialists assessing cases of possible adult CF and highlight an area in need of improvement.
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- Long Non-Coding RNA Expression in Alpha-1 Antitrypsin Deficient Monocytes Pre- and Post-AAT Augmentation Therapy. [Journal Article]
- Long non-coding RNAs (lncRNAs) regulate gene expression. Their expression in alpha-1 antitrypsin (AAT) deficiency has not been investigated. Treatment of AAT deficiency involves infusion of plasma-purified AAT and this augmentation therapy has previously been shown to alter microRNA expression in monocytes of AAT-deficient (ZZ) individuals. Here, we assess the effect of AAT augmentation therapy o…
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- Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis. [Journal Article]Cell Chem Biol. 2023 Jan 19; 30(1):22-42.e5.CC
- Genetic variation in alpha-1 antitrypsin (AAT) causes AAT deficiency (AATD) through liver aggregation-associated gain-of-toxic pathology and/or insufficient AAT activity in the lung manifesting as chronic obstructive pulmonary disease (COPD). Here, we utilize 71 AATD-associated variants as input through Gaussian process (GP)-based machine learning to study the correction of AAT folding and functi…
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- Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts. [Journal Article]
- (1) Background: The inherited alpha-1 antitrypsin (A1AT) deficiency variant 'Pi*Z' emerged as a genetic modifier of chronic liver disease. Controversial data exist on the relevance of heterozygous Pi*Z carriage ('Pi*MZ' genotype) as an additional risk factor in patients with chronic viral hepatitis C to develop progressive liver fibrosis. (2) Methods: Two prospectively recruited cohorts totaling …
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- Modeling bile duct ischemia and reoxygenation injury in human cholangiocyte organoids for screening of novel cholangio-protective agents. [Journal Article]
- CONCLUSIONS: These findings demonstrate that ICOs recapitulate ischemic cholangiopathy in vitro and enable drug assessment studies for the discovery of new therapeutics for ischemic cholangiopathies.
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- Blood concentrations of mediators released from activated neutrophils are related to the severity of alcohol-induced liver damage. [Journal Article]
- CONCLUSIONS: Our results point out the critical role of neutrophils in the pathogenesis of ALD. NE and MPO correlated with the intensity of inflammation, and NE was related to the severity of liver dysfunction.
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- Safety of Intravenous Administration of an AAV8 Vector Coding for an Oxidation Resistant Human α1-antitrypsin for the Treatment of α1-antitrypsin Deficiency. [Journal Article]Hum Gene Ther. 2023 Jan 06 [Online ahead of print]HG
- α1-antitrypsin (AAT) deficiency is a common autosomal recessive hereditary disorder, with a high risk for the development of early onset panacinar emphysema. AAT produced primarily in the liver, functions to protect the lung from neutrophil protease; with AAT deficiency, unimpeded neutrophil proteases destroy the lung parenchyma. AAT is susceptible to oxidative damage resulting in an inability to…
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- NET-borne elastase prevents inflammatory relapse in intercritical gout. [Journal Article]Arthritis Rheumatol. 2022 Dec 27 [Online ahead of print]AR
- CONCLUSIONS: ULT causes shrinkage of the tophi reflected by an increase of the level of serum cell-free DNA. In the resolution phase of murine tophi, the NET-associated neutrophil elastase degrades proinflammatory cytokines and, thus, ameliorates inflammation.
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- Surf4, cargo trafficking, lipid metabolism, and therapeutic implications. [Journal Article]J Mol Cell Biol. 2022 Nov 29 [Online ahead of print]JM
- Surfeit 4 is a polytopic transmembrane protein that primarily resides in the endoplasmic reticulum (ER) membrane. It is ubiquitously expressed and functions as a cargo receptor, mediating cargo transport from the ER and the Golgi apparatus via the canonical coat protein complex II (COPII)-coated vesicles or specific vesicles. It also participates in ER-Golgi protein trafficking through a tubular …
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- Corroboration of cross-reactivity between Mycobacterium leprae and hosts' salivary and cutaneous proteins: A hope for prognostic biomarkers for the pathogenesis of reactions in leprosy. [Journal Article]
- Immunological reactions are frequent complications that may occur either before, during, or after treatment and affect 30-50% of leprosy patients. The presence of autoantibodies like rheumatoid factor, antinuclear factor, and antibodies to host collagen, keratin, actin, myosin, endothelial cells, and myelin basic protein (MBP) has been earlier reported in leprosy patients. The purpose of this stu…
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- Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept. [Journal Article]
- Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy fo…
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- Abnormal Alpha-1 Antitrypsin Levels and Other Risk Factors Associated with Lung Function Impairment at 6 and 12 Months after Hospitalization Due to COVID-19: A Cohort Study. [Journal Article]
- Respiratory function deficits are common sequelae for COVID-19. In this study, we aimed to identify the medical conditions that may influence lung function impairment at 12 months after SARS-CoV2 infection and to analyze the role of alpha-1 antytripsin (AAT) deficiciency (AATD). A cohort study was conducted on hospitalized COVID-19 pneumonia patients in Granada (Spain) during the first infection …
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- The Influence of Ambient Temperature Changes on the Indicators of Inflammation and Oxidative Damage in Blood after Submaximal Exercise. [Journal Article]
- Physical activity has a positive effect on human health and well-being, but intense exercise can cause adverse changes in the organism, leading to the development of oxidative stress and inflammation. The aim of the study was to determine the effect of short-term cold water immersion (CWI) and a sauna bath as methods of postexercise regeneration on the indicators of inflammation and oxidative dam…
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- Genetic and Serum Screening for Alpha-1-Antitrypsin Deficiency in Adult Patients with Cystic Fibrosis: A Single-Center Experience. [Journal Article]
- Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two of the commonest genetic diseases affecting the Caucasian population. Neutrophil-mediated inflammation due to protease-antiprotease imbalance leads to progressive pulmonary involvement in both diseases. The aim of this study was to investigate the prevalence of AAT deficiency in CF adults. A prospective study enrolling CF adult…
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- Registry-based cohort study of alpha-1 antitrypsin deficiency prevalence, incidence and mortality in Denmark 2000-2018. [Journal Article]
- CONCLUSIONS: Diagnosed AATD was associated with increased mortality, especially for children. The finding for children was based on few deaths and had very wide 95% CIs.
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- Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency. [Journal Article]Respiration. 2022 Dec 22 [Online ahead of print]R
- CONCLUSIONS: EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.
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- Alpha-1 antitrypsin expression is upregulated in multidrug-resistant cancer cells. [Journal Article]Histochem Cell Biol. 2022 Dec 19 [Online ahead of print]HC
- Identification of the signature molecular profiles involved in therapy resistance is of vital importance in developing new strategies for treatments and disease monitoring. Protein alpha-1 antitrypsin (AAT, encoded by SERPINA1 gene) is an acute-phase protein, and its high expression has been linked with unfavorable clinical outcome in different types of cancer; however, data on its involvement in…
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- Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. [Journal Article]
- CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www.
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- Role and mechanism of alpa1-antitrypsin in polycystic ovary syndrome. [Journal Article]Saudi Med J. 2022 Dec; 43(12):1309-1316.SM
- CONCLUSIONS: Alpha1-antitrypsin is closely associated with NE, IL-1β, and IL-8. Therefore, we speculate that A1AT might ameliorate PCOS symptoms by inhibiting pro-inflammatory factors: NE, IL-1β, and IL-8.
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- Plasma markers of COVID-19 severity: a pilot study. [Journal Article]
- CONCLUSIONS: COVID-19-associated changes in levels and N-glycosylation of specific plasma proteins highlight complexity of inflammatory process and grant further investigations.
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- Alpha-1-Antitrypsin Pi*MZ variant increases risk of developing hepatic events in nonalcoholic fatty liver disease patients. [Journal Article]Clin Res Hepatol Gastroenterol. 2022 Dec 09; 47(2):102066.CR
- CONCLUSIONS: Patients with NAFLD and A1AT Pi*MZ variant are at increased risk for developing hepatic decompensation. NAFLD patients should be offered A1AT genotyping for risk stratification, counseling, and multidisciplinary intervention for NAFLD.
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- Structural characterization and conformational dynamics of alpha-1 antitrypsin pathogenic variants causing alpha-1-antitrypsin deficiency. [Journal Article]
- Background: Alpha-1 antitrypsin deficiency (A1ATD) is a progressive lung disease caused by inherited pathogenic variants in the SERPINA1 gene. However, their actual role in maintenance of structural and functional characteristics of the corresponding α-1 anti-trypsin (A1AT) protein is not well characterized. Methods: The A1ATD causative SERPINA1 missense variants were initially collected from var…
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- New variants of alpha-1-antitrypsin: structural simulations and clinical expression. [Journal Article]
- CONCLUSIONS: The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed.
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- Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity. [Journal Article]
- Individuals homozygous for the "Z" mutation in alpha-1 antitrypsin deficiency are known to be at increased risk for liver disease. It has also become clear that some degree of risk is similarly conferred by the heterozygous state. A lack of model systems that recapitulate heterozygosity in human hepatocytes has limited the ability to study the impact of a single Z alpha-1 antitrypsin (ZAAT) allel…
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- A randomized controlled pilot trial of etanercept and alpha-1 antitrypsin to improve autologous islet engraftment. [Randomized Controlled Trial]
- CONCLUSIONS: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment.
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