Clinical features in patients with severe Alpha-1 antitrypsin deficiency due to rare genotypes.

Alpha-1 Antitrypsin Deficiency (AATD) is a co-dominant condition associated with an increased risk of lung and liver disease. Since it is commonly thought that 95% of severe cases of AATD have PI*ZZ genotype, most studies about AATD have been focused on the Z variant. Nevertheless, over 500 single nucleotide variations in the gene have been identified.

Quantification of circulating alpha-1-antitrypsin polymers associated with different genotypes.

Objectives: Alpha-1-antitrypsin deficiency is a genetic disorder caused by mutations in the gene encoding alpha-1-antitrypsin (AAT), the major serine protease inhibitor in plasma. Reduced AAT levels are associated with elevated risk of developing emphysema mainly due to uncontrolled activity of neutrophil elastase in the lungs. The prevalent Z-AAT mutant and many rare pathogenic AAT variants also predispose to liver disease due to their accumulation as polymeric chains in hepatocytes.

Sanger and Next-Generation Sequencing of AAT.

Sequencing of DNA is normally the final procedure carried out to determine the actual pathogenic variants when the techniques used for genotyping are unable to provide complete identification of both AAT alleles. Gene sequencing of complete SERPINA1 gene by using the Sanger method or next-generation sequencing (NGS) is crucial to enable correct diagnosis in patients with alpha1-antitrypsin deficiency caused by uncommon AAT variants.This protocol explains how to correctly sequence SERPINA1 gene both with Sanger method and NGS.

Transplant with MZ genotype liver: what is the clinical pulmonary picture after 30 years? a case report and review of the literature.

Background: Alpha-1 antitrypsin, also known as alpha1 proteinase inhibitor, is a protein 90% synthesized by hepatocytes. Alpha-1 antitrypsin deficiency should be suspected if patients have unexplained emphysema or liver disease in the absence of others recognized causes. The diagnosis is based on tests that measure the amount of the enzyme in the blood and confirm by molecular analysis.

Smart Sensors and Microtechnologies in the Precision Medicine Approach against Lung Cancer.

Background And Rationale: The therapeutic interventions against lung cancer are currently based on a fully personalized approach to the disease with considerable improvement of patients' outcome. Alongside continuous scientific progresses and research investments, massive technologic efforts, innovative challenges, and consolidated achievements together with research investments are at the bases of the engineering and manufacturing revolution that allows a significant gain in clinical setting.

Aim And Methods: The scope of this review is thus to focus, rather than on the biologic traits, on the analysis of the precision sensors and novel generation materials, as semiconductors, which are below the clinical development of personalized diagnosis and treatment.

Practical dietary advices for subjects with alpha-1 antitrypsin deficiency.

Congenital alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by the mutation of the SERPINA1 gene on chromosome 14. At pulmonary level, AAT deficiency leads to an increased risk of chronic obstructive pulmonary disease (COPD) and emphysema, starting from the third-fourth decade of life. At hepatic level, some variants of the allelic, in particular PI*Z, cause a conformational change of the AAT molecule, which polymerizes within the hepatocytes.

Comprehensive Clinical Diagnostic Pipelines Reveal New Variants in Alpha-1 Antitrypsin Deficiency.

Alpha-1 antitrypsin deficiency (AATD) is an underdiagnosed disorder associated with mutations in the gene encoding alpha-1 antitrypsin (AAT). Severe AATD can manifest as pulmonary emphysema and progressive liver disease. Besides the most common pathogenic variants S (E264V) and Z (E342K), many rarer genetic variants of AAT have been found in patients and in the general population.

Comparison among populations with severe and intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease.

Background: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM).

The Genes-Stemness-Secretome Interplay in Malignant Pleural Mesothelioma: Molecular Dynamics and Clinical Hints.

MPM has a uniquely poor somatic mutational landscape, mainly driven by environmental selective pressure. This feature has dramatically limited the development of effective treatment. However, genomic events are known to be associated with MPM progression, and specific genetic signatures emerge from the exceptional crosstalk between neoplastic cells and matrix components, among which one main area of focus is hypoxia.

Improving the Laboratory Diagnosis of M-like Variants Related to Alpha1-Antitrypsin Deficiency.

Alpha1-antitrypsin (AAT) is a serine protease inhibitor that is encoded by the highly polymorphic gene. Mutations in this gene can lead to AAT deficiency (AATD), which is associated with an increased risk of lung and/or liver disease. On the basis of electrophoretic migration, AAT variants are named with capital letters; M (medium) signifies the normal protein.

Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy.

Background: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy.

Objectives: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy.

Clinical manifestations of a new alpha-1 antitrypsin genetic variant: .

Alpha-1 antitrypsin deficiency is an autosomal, codominant disorder caused by mutations of the gene. Several mutations of have been described associated with the development of pulmonary emphysema and/or chronic liver disease and cirrhosis. Here, we report a very rare variant identified for the first time in an Italian family originally from the city of Parma in Northern Italy.

An Italian expert consensus on the management of alpha1-antitrypsin deficiency: a comprehensive set of algorithms.

Background: Alpha1-antitrypsin deficiency (AATD) is a genetic-based risk condition, mainly affecting the lungs and liver. Despite its wide distribution, it is largely underdiagnosed, thus being considered a rare disease, and is consequently managed in ad-hoc reference centers. Unfortunately, an easy-to-use algorithm for managing such a complex disease is still lacking.

Investigating the Link between Alpha-1 Antitrypsin Deficiency and Abdominal Aortic Aneurysms.

Background: Alpha-1-Antitrypsin (AAT) is one of the major plasmatic protease inhibitors. In the last decade, an association between Alpha-1-Antitrypsin Deficiency (AATD) and Abdominal Aortic Aneurysms (AAA) has been hypothesized. Multiple factors may be involved in AAA's etiopathogenesis, and an underlying structural defect of the extracellular matrix (ECM) is always present.

The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant.

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap.

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

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.

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

Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency.

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.

Air Trapping Is Associated with Heterozygosity for Alpha-1 Antitrypsin Mutations in Patients with Asthma.

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder involving lungs, characterized by low serum concentration of the protein alpha-1 antitrypsin (AAT) also called proteinase inhibitor (PI). Asthma is common in AATD patients, but there are only few data on respiratory function in asthmatic patients with AATD.

Objectives: The aim of the study was to evaluate lung function in asthmatic outpatients with mutation in the SERPINA1 gene coding for AAT versus asthmatic subjects without mutation.

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

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.