Description
Alpha-1-antitrypsin Deficiency: Biology, Diagnosis, Clinical Significance, and Emerging Therapies is the authoritative reference on AATD, providing standards for diagnosis, monitoring, treatment and appropriate avenues of research.
The book covers the disease from basic biology and epidemiology, to clinical impact, and includes the understanding of the natural history of the disease and the significant advances that have been made in the last 20 years, including the three-dimensional structure of the molecule, its broad biological activity and improved therapeutic options, including replacement therapy and gene therapy.
The editors have recruited international experts in the field to contribute evidence-based chapters and insights on future developments in the understanding of this disease.
- Provides documentation of the variations in clinical presentation and pathology in a single reference
- Presents new insights by pulling together the advances in the understanding of the structure and function of alpha1-antitrypsin deficiency with the genetic variants that cause the disease
- Allows for easy reference for the diagnosis of AATD to lead to better therapeutics
Chapter
Chapter 1 - Historical Perspective
The discovery of alpha-1-antitrypsin deficiency (AATD)
AATD and association with pulmonary emphysema
AATD and association with liver disease
Other disease associations
Chapter 2 - The Swedish Alpha-1-Antitrypsin Screening Study: What We Have Learnt From Birth to Adult Life
Adolescence and Young Adulthood
Adaptive Biochemical Changes
Psychological Effects of the Neonatal Alpha-1-Antitrypsin Screening
Chapter 3 - Alpha-1-Antitrypsin Gene Regulation
AAT, acute-phase, and tissue expression
The Serpin cluster on 14q31-31.2, the AAT gene, and transcripts
AAT hepatocyte promoter and enhancers
Control of AAT expression in nonhepatic tissue
AAT locus control region and interaction with transcription factors
Chapter 4 - Alpha-1-Antitrypsin Variants
Alpha-1-antitrypsin nomenclature and isoelectric focusing
Chapter 5 - Alpha1-Antitrypsin: Structure and Dynamics in Health, Disease and Drug Development
Why Understanding the Conformational Behavior of Alpha1-Antitrypsin Matters in Alpha1-Antitrypsin Deficiency
Conformational states associated with function and dysfunction
Complexed With Protease as a Consequence of the Functional Mechanism
How Structure Determines Function
Finding of Polymers in Disease
Dynamics of Native Wild-Type Alpha1-Antitrypsin in Solution
Alpha1-Antitrypsin Folding: How Does It Go Right, How Does It Go Wrong?
How Does Alpha1-Antitrypsin Avoid Folding to the Inactive Latent Conformation?
Intracellular Misfolding and Polymerization of Alpha1-Antitrypsin
In vitro studies of Alpha1-Antitrypsin polymerization: lessons and limitations
Different Alpha1-Antitrypsin Polymers Form in Different Experimental Conditions
Studies of M*: the Polymerogenic Intermediate State
Disulfide Locking of Intracellular Polymers
Other Polymeric Architectures Observed In Vitro
Relating Deficiency Mutations to Disease Phenotype
Translating to New Therapeutic Strategies: Stabilizing Alpha1-Antitrypsin Against Pathological Conformational Change
Polymerization Blockade by a Monoclonal Antibody
Blockade of Disease-Associated Dynamics
Studying polymerization in cells, organisms, and clinical samples
Chapter 6 - Novel Biological Functions of A1AT
A1AT is a broad-spectrum inhibitor of proteases
A1AT as an antiinflammatory and immunomodulatory protein
Modified molecular forms of A1AT and their biological functions
A1AT Complexes With Other Proteins
A1AT Complexes With Lipids
A1AT Binds Free Fatty Acids and Upregulates Angptl4
Plasma purified A1AT as an antiinflammatory drug
Chapter 7 - AATD and Lung Disease
Evaluation and progression
Noninhibitory functions of AAT
Chapter 8 - Alpha-1-Antitrypsin Deficiency Liver Disease
Heterozygotes and other genotypes
Molecular and cellular pathophysiology of AAT ZZ liver disease
New therapeutic technologies
Chapter 9 - Alpha-1-Antitrypsin Deficiency: Epidemiological Studies and Other AATD Associated Diseases
The prevalence of alpha-1-antitrypsin deficiency
Evidence that alpha-1–antitrypsin deficiency is under-recognized
Detection and diagnosis of AATD-associated liver disease
Other proposed disease associations
Chapter 10 - Thoracic CT Imaging in AATD
Emphysema: the pathological basis for defining emphysema
The role of Computed Tomography in phenotyping AATD-associated lung disease
CT assessment of airways disease
Incidental pulmonary nodules
The validation and acceptance of CT densitometry as an outcome measure
Chapter 11 - Animal Models of Alpha-1-Antitrypsin Deficiency
Role of animal models in understanding lung disease
Proteinase–antiproteinase hypothesis
Naturally occurring animal model of genetic alpha-1 antitrypsin deficiency
Other naturally occurring animal models of emphysema
Genetically modified animal models
Protease inhibitor knockout mouse models
Z Alpha-1 Antitrypsin Over Expression Model
Functional Properties of Antitrypsin
Inhalation of Antiproteinase
Future Objectives and Conclusion
Chapter 12 - Establishing European Registries for AATD and Clinical Trials for Lung Disease
History of choice of cross-sectional data collection for the AIR database
Initial choices of items to collect and definition of a minimal data set for entry of patients
Subsequent additions: gas transfer and health status questionnaire results
Improvements of quality control on data entry
Description of the cross-sectional data collected over 15 years
History of prospective data collection for the AIR database
Spin-off: a database for children with alpha-1-antitrypsin deficiency
Description of prospective data collected over 5 years
Impact of replacement therapy for lung disease
Chapter 13 - Establishing the USA Registry: Logistics, Impact, and Early Clinical Trials
AAT augmentation therapy in the NHLBI Registry
The Alpha-1 Foundation Research Registry
The Alpha Coded Testing (ACT) Study for home diagnostic testing
Chapter 14 - Gene Therapy
General principles of gene therapy
Animal models of gene therapy
Features of vectors used in gene therapy studies of AATD
Human trials of gene therapy
Chapter 15 - The Future of Alpha-1-Antitrypsin Research
Summary of progress to date
What are some of the important questions for future research?
Alpha-1-antitrypsin Deficiency
：Biology, Diagnosis, Clinical Significance, and Emerging Therapies
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