1,114 results match your criteria Alpha1-Antitrypsin Deficiency


Mesenchymal Stromal Cell Secretome for Post-COVID-19 Pulmonary Fibrosis: A New Therapy to Treat the Long-Term Lung Sequelae?

Cells 2021 05 14;10(5). Epub 2021 May 14.

Center for Diagnosis of Inherited Alpha1-Antitrypsin Deficiency, Department of Internal Medicine and Therapeutics, Pneumology Unit IRCCS San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy.

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Read More

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Scaling Concepts in Serpin Polymer Physics.

Materials (Basel) 2021 May 15;14(10). Epub 2021 May 15.

Institute of Biophysics, National Research Council of Italy, via Ugo La Malfa 153, 90146 Palermo, Italy.

α1-Antitrypsin is a protease inhibitor belonging to the serpin family. Serpin polymerisation is at the core of a class of genetic conformational diseases called serpinopathies. These polymers are known to be unbranched, flexible, and heterogeneous in size with a beads-on-a-string appearance viewed by negative stain electron microscopy. Read More

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[Alpha-1 antitrypsin deficiency: cause and cofactor for liver disease].

Dtsch Med Wochenschr 2021 Jun 1;146(11):714-718. Epub 2021 Jun 1.

Medizinische Klinik III, Gastroenterologie, Stoffwechselerkrankungen und Intensivmedizin, Uniklinik Aachen, Aachen, Deutschland.

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder arising due to mutation in alpha1-antitrypsin (AAT). AAT mutations interfere with the AAT production/secretion, cause decreased AAT serum levels and accumulation of AAT in the liver. The excess AAT leads to a proteotoxic liver disease, while the lack of AAT in systemic circulation predisposes to lung injury. Read More

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Nonpancreatic Pancreatic Panniculitis: An Incidental Finding in Individuals without Pancreatic Disease? A Case Series and Review of the Literature.

J Clin Aesthet Dermatol 2021 Apr 1;14(4):28-30. Epub 2021 Apr 1.

Dr. Milani-Nejad is with the Department of Dermatology at the University of California in Los Angeles, California.

Pancreatic panniculitis occurs in up to three percent of all patients with pancreatic disease. This cutaneous eruption, as implied by the name, is almost exclusively encountered in the context of pancreatic disorders, such as pancreatitis or pancreatic carcinoma. We report three cases in which histopathologic examination demonstrated hallmarks of pancreatic panniculitis occurring in patients without any history or evidence of pancreatic disorder. Read More

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Do gene-environment interactions play a role in COVID-19 distribution? The case of Alpha-1 Antitrypsin, air pollution and COVID-19.

Multidiscip Respir Med 2021 Jan 22;16(1):741. Epub 2021 Apr 22.

INSERM and Sorbonne University, Epidemiology of Allergic and Respiratory Diseases Department, IPLESP, Paris, France.

Background: Gene-environment interactions are relevant for several respiratory diseases. This communication raises the hypothesis that the severity of COVID-19, a complex disease where the individual response to the infection may play a significant role, could partly result from a gene-environment interaction between air-pollution and Alpha-1 Antitrypsin (AAT) genes.

Methods: To evaluate the impact of the AAT and air pollution interaction on COVID-19, we introduced an AAT*air pollution global risk score summing together, in each country, an air pollution score (ozone, nitrogen dioxide and fine particulate matter) and an AAT score (which sums the ranked frequency of MZ, SZ, MS). Read More

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January 2021

SARS-CoV-2 infection in alpha1-antitrypsin deficiency.

Respir Med 2021 Aug 13;184:106466. Epub 2021 May 13.

Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany; Coordinating Center for Alpha-1 Antitrypsin Deficiency-related Liver Disease of the European Reference Network (ERN) "Rare Liver" and the European Association for the Study of the Liver (EASL) Registry Group "Alpha-1 Liver", Germany. Electronic address:

Alpha1-antitrypsin deficiency arises due to mutations in alpha1-antitrypsin (AAT) gene and represents the most prominent genetic predisposition to chronic obstructive pulmonary disease and emphysema. Since AAT plays important immunomodulatory and tissue-protective roles and since it was suggested to protect from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we assessed this association in United Kingdom Biobank, a community-based cohort with >500,000 participants. The most common, mild AATD genotypes were associated neither with increased SARS-CoV-2 infection rates nor with increased SARS-CoV-2 fatalities, while the numbers of severe AATD cases were too low to allow definitive conclusions. Read More

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Pleiotropic associations of heterozygosity for the Z allele in the UK Biobank.

ERJ Open Res 2021 Apr 10;7(2). Epub 2021 May 10.

Division of Respiratory Medicine, University of Nottingham, and NIHR Nottingham BRC, NUH NHS Trust, Nottingham, UK.

Homozygosity for the Z allele causes α-antitrypsin deficiency, a rare condition that can cause lung and liver disease. However, the effects of Z allele heterozygosity on nonrespiratory phenotypes, and on lung function in the general population, remain unclear. We conducted a large, population-based study to determine Z allele effects on >2400 phenotypes in the UK Biobank (N=303 353). Read More

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COVID-19 infection in severe Alpha 1-antitrypsin deficiency: Looking for a rationale.

Respir Med 2021 07 30;183:106440. Epub 2021 Apr 30.

Centre for Diagnosis of Inherited Alpha-1 Antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease, Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

The clinical manifestations of COVID-19 are heterogeneous: 46.4% of patients admitted into hospital reported to have at least one comorbidity. Comorbidities such as COPD, diabetes, hypertension and malignancy predispose patients with Covid-19 to adverse clinical outcomes. Read More

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Alpha-antitrypsin Disease, Treatment and Role for Lung Volume Reduction Surgery.

Thorac Surg Clin 2021 May;31(2):139-160

Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Southern Illinois University School of Medicine, 801 North Rutledge Street, Room 1269, Springfield, IL 62702, USA.

Chronic obstructive pulmonary usually is subcategorized into 2 groups: chronic bronchitis and emphysema. The main cause of chronic bronchitis and emphysema is smoking; however, alpha1-antitrypsin also has been seen to cause emphysema in patients who are deficient. As symptoms and lung function decline, treatment modalities, such as lung volume reduction surgery, have been used in individuals with chronic obstructive pulmonary disease and upper lobe predominant emphysema. Read More

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Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency.

J Clin Med 2021 Apr 16;10(8). Epub 2021 Apr 16.

Pneumology Department, Hospital Universitari Vall d'Hebron/Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, 08035 Barcelona, Spain.

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Read More

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Alpha-1 Antitrypsin Screening in a Selected Cohort of Patients Affected by Chronic Pulmonary Diseases in Naples, Italy.

J Clin Med 2021 Apr 7;10(8). Epub 2021 Apr 7.

Unit of Respiratory Physiopathology, Department of Critic Area, Monaldi Hospital, 80131 Naples, Italy.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition associated with several respiratory diseases in patients with severe protein deficiency. AATD is often late diagnosed or underdiagnosed. Diagnosis frequently occurs in patients with chronic obstructive pulmonary disease and emphysema characterized by frequent exacerbations and over ten years' duration. Read More

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Therapeutic SERPINs: Improving on Nature.

Front Cardiovasc Med 2021 31;8:648349. Epub 2021 Mar 31.

CDL Research, University Medical Center Utrecht, Utrecht, Netherlands.

Serine proteases drive important physiological processes such as coagulation, fibrinolysis, inflammation and angiogenesis. These proteases are controlled by serine protease inhibitors (SERPINs) that neutralize their activity. Currently, over 1,500 SERPINs are known in nature, but only 37 SERPINs are found in humans. Read More

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Shear Wave Elastography and Shear Wave Dispersion Imaging in the Assessment of Liver Disease in Alpha1-Antitrypsin Deficiency.

Diagnostics (Basel) 2021 Mar 31;11(4). Epub 2021 Mar 31.

Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

Liver affection of Alpha1-antitrypsin deficiency (AATD) can lead to cirrhosis and hepatocellular carcinoma (HCC). A noninvasive severity assessment of liver disease in AATD is urgently needed since laboratory parameters may not accurately reflect the extent of liver involvement. Preliminary data exist on two-dimensional shear wave elastography (2D-SWE) being a suitable method for liver fibrosis measurement in AATD. Read More

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Commercial α1-antitrypsin preparations markedly differ in their potential to inhibit the ATP-induced release of monocytic interleukin-1β.

Pulm Pharmacol Ther 2021 Jun 25;68:102020. Epub 2021 Mar 25.

Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University, Giessen, Germany; Member of the German Centre for Lung Research (DZL), Germany. Electronic address:

The acute phase protein α1-antitrypsin (AAT) inhibits numerous proteases, specifically neutrophil elastase. Patients with an AAT deficiency due to mutations frequently develop early onset emphysema. The commercial preparations of human plasma AAT are clinically used as biopharmaceuticals to protect the lung tissue of AAT-deficient patients from damage caused by neutrophil elastase. Read More

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FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD.

BMJ Open 2021 03 22;11(3):e042526. Epub 2021 Mar 22.

Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.

Introduction: A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352. Read More

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The development of highly potent and selective small molecule correctors of Z α-antitrypsin misfolding.

Bioorg Med Chem Lett 2021 Jun 19;41:127973. Epub 2021 Mar 19.

UCL Respiratory, Rayne Institute, University College London, London WC1E 6JF, United Kingdom.

α1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant α1-antitrypsin protein within the endoplasmic reticulum (ER) of hepatocytes. Small molecules that bind and stabilise Z α-antitrypsin were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to a series of highly potent, selective and cellular active α1-antitrypsin correctors. Read More

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Impact of serine protease inhibitor alpha1-antitrypsin on expression of endoplasmic reticulum stress-induced proinflammatory factors in adipocytes.

Biochem Biophys Rep 2021 Jul 2;26:100967. Epub 2021 Mar 2.

Department of Endocrine Pharmacology, Tokyo University of Pharmacy & Life Sciences, Horinouchi 1432-1, Hachioji, Tokyo, 192-0392, Japan.

Obesity-induced endoplasmic reticulum (ER) stress contributes to low-grade chronic inflammation in adipose tissue and may cause metabolic disorders such as diabetes mellitus and dyslipidemia. Identification of high serpina A1 (alpha-1 antitrypsin, A1AT) expression in mouse adipose tissue and adipocytes prompted us to explore the role of A1AT in the inflammatory response of adipocytes under ER stress. We aimed to determine the role of A1AT expression in adipocytes with ER stress during regulation of adipocyte homeostasis and inflammation. Read More

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Comparison of different algorithms in laboratory diagnosis of Alpha1-antitrypsin deficiency.

Clin Chem Lab Med 2021 Mar 5. Epub 2021 Mar 5.

Centre for Diagnosis of Inherited Alpha-1 Antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute for Respiratory Disease, Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.

Objectives: Alpha1-antitrypsin deficiency (AATD) is an inherited condition that predisposes individuals to an increased risk of developing lung and liver disease. Even though AATD is one of the most widespread inherited diseases in Caucasian populations, only a minority of affected individuals has been detected. Whereas methods have been validated for AATD testing, there is no universally-established algorithm for the detection and diagnosis of the disorder. Read More

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Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes.

Dev Cell 2021 Mar 4;56(6):747-760.e6. Epub 2021 Mar 4.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:

Loss of insulin-secreting pancreatic β cells through apoptosis contributes to the progression of type 2 diabetes, but underlying mechanisms remain elusive. Here, we identify a pathway in which the cell death inhibitor ARC paradoxically becomes a killer during diabetes. While cytoplasmic ARC maintains β cell viability and pancreatic architecture, a pool of ARC relocates to the nucleus to induce β cell apoptosis in humans with diabetes and several pathophysiologically distinct mouse models. Read More

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Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis.

Proc Natl Acad Sci U S A 2021 Mar;118(10)

Telethon Institute of Genetics and Medicine, Pozzuoli, 80078 Naples, Italy;

α1-Antitrypsin (AAT) deficiency is a common genetic disease presenting with lung and liver diseases. AAT deficiency results from pathogenic variants in the gene encoding AAT and the common mutant Z allele of encodes for Z α1-antitrypsin (ATZ), a protein forming hepatotoxic polymers retained in the endoplasmic reticulum of hepatocytes. PiZ mice express the human ATZ and are a valuable model to investigate the human liver disease of AAT deficiency. Read More

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A rare mutation on alpha-1 antitrypsin deficit and lung fibrosis: case report.

Sarcoidosis Vasc Diffuse Lung Dis 2020 16;37(4):e2020019. Epub 2020 Dec 16.

Department of Pulmonology at Centro Hospitalar de Trás-os-Montes e Alto Douro, Vila Real, Portugal.

Alpha1-antitrypsin deficiency (AATD) is an autosomal codominant disease, and different genetic variants are known, some of which very rare. Usual pulmonary manifestations include emphysema, bronchiectasis and asthma. Pulmonary fibrosis is uncommon. Read More

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December 2020

Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2.

J Pathol 2021 May 18;254(1):80-91. Epub 2021 Mar 18.

Department of Medicine III, University Hospital Aachen, Aachen, Germany.

Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. Read More

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SARS-CoV-2 mutation 614G creates an elastase cleavage site enhancing its spread in high AAT-deficient regions.

Infect Genet Evol 2021 06 5;90:104760. Epub 2021 Feb 5.

National Institute of Biomedical Genomics, Kalyani 741251, India. Electronic address:

SARS-CoV-2 was first reported from China. Within three months, it evolved to 10 additional subtypes. Two evolved subtypes (A2 and A2a) carry a non-synonymous Spike protein mutation (D614G). Read More

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Development of a small molecule that corrects misfolding and increases secretion of Z α -antitrypsin.

EMBO Mol Med 2021 Mar 29;13(3):e13167. Epub 2021 Jan 29.

GlaxoSmithKline, Cambridge, MA, USA.

Severe α -antitrypsin deficiency results from the Z allele (Glu342Lys) that causes the accumulation of homopolymers of mutant α -antitrypsin within the endoplasmic reticulum of hepatocytes in association with liver disease. We have used a DNA-encoded chemical library to undertake a high-throughput screen to identify small molecules that bind to, and stabilise Z α -antitrypsin. The lead compound blocks Z α -antitrypsin polymerisation in vitro, reduces intracellular polymerisation and increases the secretion of Z α -antitrypsin threefold in an iPSC model of disease. Read More

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Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches.

Int J Mol Sci 2021 Jan 21;22(3). Epub 2021 Jan 21.

Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The Netherlands.

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 targets of AAT, are not sufficiently inhibited, resulting in excessive degradation of the lung parenchyma, increased inflammation, and increased susceptibility to infections. Read More

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January 2021

α1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action.

Lancet Respir Med 2021 04 21;9(4):337-339. Epub 2021 Jan 21.

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada; Institute of Medical Science, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada; Division of Respiratory Medicine, Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5G 1L7, Canada. Electronic address:

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Research priorities in α-antitrypsin deficiency: results of a patients' and healthcare providers' international survey from the EARCO Clinical Research Collaboration.

ERJ Open Res 2020 Oct 21;6(4). Epub 2020 Dec 21.

Pulmonology Dept, Centro Hospitalar do Porto, Porto, Portugal.

α-antitrypsin deficiency (AATD) is a rare and under-recognised genetic condition. Owing to its low prevalence, international initiatives are key for conducting high-quality research in the field. From July 2018 to December 2019, the European Alpha-1 Research Collaboration (EARCO) developed and conducted two surveys, one for healthcare providers and one for patients and caregivers, aiming to identify research priorities and barriers in access to treatment for AATD. Read More

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October 2020

[Erratum to "Screening for alpha1-antitrypsin deficiency using dried blood spot: Assessment of the first 20 months" [Rev. Mal. Respir. 37 (2020) 633-43]].

Rev Mal Respir 2021 Jan 17;38(1):125-126. Epub 2020 Dec 17.

CHU de Lille, laboratoire de biochimie et biologie moléculaire (HMNO), centre de biologie pathologie, boulevard du Pr.-Jules-Leclercq, 59037 Lille, France; Faculté de pharmacie et EA 7364 RADEME, laboratoire de biochimie et biologie moléculaire, université de Lille, Lille, France.

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January 2021