Blanco's Overview of Alpha-1 Antitrypsin Deficiency

History, Biology, Pathophysiology, Related Diseases, Diagnosis and Treatment

Ignacio Blanco

• Publisher: Academic Press
• Year: 2017
• Print ISBN:
  9780128095300
• eBook ISBN:
  9780128095416
• Topic: Medicine
• Subtopic: Neurology

Blanco's Overview of Alpha-1 Antitrypsin Deficiency: History, Biology, Pathophysiology, Related Diseases, Diagnosis, and Treatment is a robust introduction to topics associated with Alpha-1 Antitrypsin Deficiency (AATD). Included are topics ranging from the history of the disease, biology, pathophysiology, related diseases, including the two major manifestations of the disease (liver disease and lung disease), and diagnosis and treatment. The book addresses the need for the amalgamation of current and novel concepts and practices in the field of AATD. AATD is under-recognized in the medical community and, as a result, it is underdiagnosed. The book provides increased awareness and understanding of the condition to improve diagnosis rates and enhance patient care. This book is an essential tool and reference, beneficial to clinicians who screen and treat AATD patients, as well as research scientists working in the AATD field at junior and senior levels. - Presents the fundamental theoretical and practical aspects of Alpha-1 Antitrypsin Deficiency (AATD) based on scientific evidence - Provides evidence to show that AATD is a rarely diagnosed condition, rather than a rare condition - Contains current research and future perspectives from Dr. Ignacio Blanco, a worldwide expert in the field of alpha-1 antitrypsin and lung and liver disease associated with the deficiency of this antiprotease - Provides resources to current registries and patient associations

Chapter 1

Alpha-1 Antitrypsin Deficiency: Introduction and History

Abstract

After the discovery of the alpha-1 antitrypsin (AAT) deficiency–related lung emphysema by Laurell and Ericksson in Malmo (Sweden) 52 years ago, it took nearly a decade to discover its relationship with liver cirrhosis and neutrophilic panniculitis. Almost 30 years ago (1987), the US Food and Drugs Administration (FDA) approved Prolastin (purified AAT obtained from pooled human serum) for augmentation therapy in patients with severe AAT deficiency, suffering from pulmonary emphysema. In the 1990s, systemic vasculitis was added to the initial list of AAT deficiency–related diseases, and since then powerful patients’ associations and registries were created worldwide with the aim of promoting research and facilitating the patients’ diagnosis and access to treatment of this genetic condition. In the last 15 years, a growing number of new AAT antiinflammatory and immunomodulatory properties have been identified, suggesting multiple potential indications for a number of diseases, both inside and outside of the context of AAT deficiency. Lately the most advanced lines of research have been implemented using this condition as a model with the ultimate goal of achieving a cure. This introductory chapter aims to be a general introduction to the basic aspects of the AAT deficiency and to briefly report its exciting exemplary history.

Keywords

alpha-1 antitrypsin

alpha-1 antitrypsin deficiency

alpha-1 antitrypsin deficiency history

1.1. Introduction

Human alpha-1 antitrypsin (AAT), also known as alpha-1 proteinase inhibitor (α1-Pi) and SERPINA1 (serine protease inhibitor, group A, member 1), is a circulating glycoprotein whose main function is to inhibit neutrophil elastase and other serine proteases in blood and tissues [1].

AAT is the most abundant circulating protease inhibitor existing in human body. This glycoprotein is mainly synthesized and secreted by hepatocytes, and its main physiological function is to protect the matrix proteins of the lungs (especially elastin) from the proteolytic effects of proteases (especially neutrophil elastase and proteinase 3) released by activated and dying neutrophils [1,2].

The AAT gene locus is located in chromosome 14, and it is activated by byproducts generated during inflammatory or infectious processes [3]. The gene has two alleles, which are transmitted from parents to childr...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• Dedication
• Preface
• Acknowledgments
• Chapter 1: Alpha-1 Antitrypsin Deficiency: Introduction and History
• Chapter 2: Serpins and Serpinopathies
• Chapter 3: Alpha-1 Antitrypsin Biology
• Chapter 4: Alpha-1 Antitrypsin Gene, Genetic Heritage, Phenotypes, and Genotypes
• Chapter 5: Alpha-1 Antitrypsin Deficiency: Liver Pathophysiology
• Chapter 6: Alpha-1 Antitrypsin Deficiency: Lung Pathophysiology
• Chapter 7: Genetic Epidemiology
• Chapter 8: Laboratory Diagnosis
• Chapter 9: Clinical Diagnosis
• Chapter 10: Liver Disease Associated With Alpha-1 Antitrypsin Deficiency
• Chapter 11: Respiratory Manifestations of the Alpha-1 Antitrypsin Deficiency
• Chapter 12: Other Diseases Associated With Alpha-1 Antitrypsin Deficiency
• Chapter 13: Clinical Management and Treatment of Lung Disease
• Chapter 14: Registries and Patients’ Associations
• Chapter 15: Current Research and Future Perspectives
• Index