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Primary Immunodeficiency Disorders
A Historic and Scientific Perspective
1st Edition - August 26, 2014
Editors: Amos Etzioni, Hans D. Ochs
Language: English
Hardback ISBN:9780124071797
9 7 8 - 0 - 1 2 - 4 0 7 1 7 9 - 7
eBook ISBN:9780124115545
9 7 8 - 0 - 1 2 - 4 1 1 5 5 4 - 5
Primary Immunodeficiency Disorders: A Historic and Scientific Perspective provides a complete historical context that is crucial for students and researchers concerned with prim…Read more
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Primary Immunodeficiency Disorders: A Historic and Scientific Perspective
provides a complete historical context that is crucial for students and researchers concerned with primary immunodeficiency. When researchers have a poor understanding of the way we arrived where we are in research, they can miss important points about a disease, or miss out on how to approach new diseases. This historical knowledge of research can assist greatly by showing how it was done in the past, demonstrating the successes and failures, so that it can be done better in the future.
This book provides an understanding of the process going from clinical problem to lab and back to the clinic, based on historical experiences. Its chapters proceed from the discovery of the T and B cell lineages through the first BMT for immunodeficiency disorder; lab investigation and gene therapy for PID; the discovery of the gene for AT and its function; understanding cytokine defects; and many other stops along the way.
Facilitates communication among physicians and other investigators concerned with immunological and inflammatory diseases
Summarizes for the first time all the known facts from 60 years of primary immunodeficiency research, and teaches how an important field in medicine was established
Provides stimulating discussions on developing new medical therapies Highlights the importance of studying humans to understand mechanisms of disease that affect humans
students, scientists and practitioners in immunology, immunodeficiency, professionals in medicine. Also interesting to anyone interested in medicine, historians of science
Contributors
Foreword
Introduction
Chapter 1: Immunity: From Serendipitous Observations to Science-Based Specialty
Abstract
Serendipitous observations
A cell derives from a cell, a microorganism from a microbe
Serum therapy, active immunization and the concept of antibodies
Epicrisis
Chapter 2: Discovery of the T- and B-Cell Compartments
Abstract
Introduction
Discovery of the importance of the thymus in immune system development
En route to Bob Good’s research group in minnesota
The atmosphere in Bob Good’s laboratory
Connecting studies in chicks and immunodeficiency diseases
The key experiments in irradiated birds
The initial T- and B-cell model and its clinical implications
Basic questions posed by the separate T- and B-lineage model
The long search for the mammalian bursa-equivalent
The identification of B-lineage progenitors
An ancient blueprint for the T- and B-cell lineages
Acknowledgments
Chapter 3: Evolution of the Definition of Primary Immunodeficiencies
Abstract
Introduction
The birth of classical PIDs, illustrated by the discovery of X-linked agammaglobulinemia
The concept of PIDs with narrow phenotype, illustrated by X-linked lymphoproliferative disease
The development of PIDs with narrow phenotype, illustrated by Mendelian susceptibility to mycobacterial disease
PIDs with narrow phenotypes underlying common infections, illustrated by herpes simplex virus encephalitis of childhood
Conclusions and perspectives
Acknowledgments
Chapter 4: From Immunodeficiency to Autoimmunity
Abstract
A historical journey into recognition of immunodeficiency and autoimmunity
Autoimmunity: an often neglected feature of immune deficiency
Omenn syndrome: inflammation and autoimmunity in immune deficiency
Expanding the spectrum of autoimmunity in RAG deficiency
The lesson learned: when combined immunodeficiency and autoimmunity go hand-in-hand
Chapter 5: Immunological Tests – from the Microscope to Whole Genome Analysis
Abstract
Introduction
History of the evaluation of humoral immunity
History of the evaluation of cellular (T-cell) immunity
History of the evaluation of the IL12/23-interferon-γ circuit
History of the evaluation of NK-cell defects
History of the evaluation of Toll-like receptor defects
History of the evaluation of neutrophil immunity
History of the evaluation of the complement system
Conclusion
Acknowledgment
Chapter 6: Primary Immunodeficiency in the Developing Countries
Abstract
Introduction
History of primary immunodeficiency in Africa
History of primary immunodeficiency in the Middle East
History of primary immunodeficiency in Latin America
Chapter 7: Jeffrey Asked Us to “Do Something”! Our Journey
Abstract
Dates of description and gene discovery of major PIDDs
Chapter 8: Finally Found: The Ataxia-Telangiectasia Gene and its Function
Abstract
Defining the clinical characteristics of A-T, a slow evolution driven by serendipity and methodology
Understanding the immune deficiency in A-T
Discovery of the genetic defect in A-T
ATM mutations worldwide
Concluding remarks
Acknowledgments
Chapter 9: Wiskott–Aldrich Syndrome: from a Fatal Hematologic Disorder to a Curable Immunodeficiency
Abstract
Introduction
The discovery of WAS as a novel clinical entity
WAS is recognized as a combined immune deficiency
WAS, autoimmunity and malignancy
The discovery of the molecular basis of WAS/XLT
WIP deficiency – an autosomal recessive disorder with a WAS phenotype
Concluding remarks
Chapter 10: Neutropenia – More Genetic Defects Than Ever Expected
Abstract
Historical milestones (Fig. 10.1)
Pathological mechanisms
Clinical presentation
Treatment
Leukemia secondary to CN
Conclusion
Acknowledgments
Chapter 11: B-Cell Defects: From X-linked Recessive to Autosomal Recessive Agammaglobulinemia
Abstract
Introduction
Bruton’s original case report
Elucidation of the pathophysiology
Identification of the molecular genetic defect
The evolving clinical picture of agammaglobulinemia
Diagnosis
Treatment
Prognosis
Autosomal recessive agammaglobulinemia
Chapter 12: The Discovery of the Familial Hemophagocytosis Syndromes
Abstract
Introduction
Description: the early years
FHL and other inherited HLH conditions: the seventies
Assessment of immunologic functions: turn of the century
The genetics of HLH: an ongoing process
Pathogenesis: from macrophages to T- and NK cells
Therapy: from immunosupression and chemotherapy to stem cell transplantation
Conclusion
Acknowledgments
Chapter 13: Chronic Granulomatous Disease – from a Fatal Disease to a Curable One
Abstract
Introduction
Original descriptions
The defect
The parts
Emerging clinical reports
Cell fusions and cell-free assays
The genes
The function
Epidemiology
Residual superoxide
Interferon gamma
Survival
Bacterial infections
Fungal infections
Inflammation
Lyonization
Bone marrow transplantation
Gene therapy
Other roles for NADPH oxidase
Conclusion
Acknowledgment
Chapter 14: Severe Combined Immunodeficiency – from Discovery to Newborn Screening
Abstract
History of SCID and its treatment
Why screen for SCID?
Newborn screening
The T-cell receptor excision circle (TREC) screening test for SCID
Results to date of TREC newborn screening for SCID
TREC newborn screening – excellent, but not perfect for identifying primary immunodeficiencies
Acknowledgments
Chapter 15: Severe Combined Immunodeficiency as Diseases of Defective Cytokine Signaling
Abstract
Introduction
IL-2 and IL-2 receptors
The conundrum and the speculation that IL-2Rγ was shared by multiple cytokines, leading to the designation of this group of cytokines as the γc family of cytokines
Critical role for heterodimerization of IL-2Rβ and γc in IL-2 signaling: the association of JAK1 with IL-2Rβ and JAK3 with γc
IL-2 also activates PI 3-kinase and MAP-kinase coupled pathways
The discovery of JAK3-deficient human SCID as another form of SCID resulting from defective cytokine signaling and the development of JAK3 inhibitors as potent immunosuppressants
Discovery of IL-7Rα-deficient SCID: establishing that defective IL-7Rα-dependent signaling explains the defective T-cell development in XSCID and JAK3-deficient SCID
Defective IL-15-dependent signaling explains the NK-cell developmental defect in patients with XSCID and JAK3 deficiency
The discovery of IL-21 and finding that the B-cell defect in XSCID results AT LEAST IN PART from defective signaling by IL-21
The efficacy of bone marrow transplantation for cellular reconstitution and B-cell function in XSCID, JAK3-deficient SCID and IL-7Rα-deficient SCID
Does STAT deficiency result in SCID?
IL-21R-deficient patients
Conclusions
Acknowledgments
Chapter 16: The Hyper IgM Syndromes – a Long List of Genes and Years of Discovery
Abstract
Introduction
CSR-D caused by a defect in T:B cooperation
X-linked CSR-D due to CD40L deficiency
Autosomal recessive CSR-D due to CD40 deficiency
X-linked CSR-D due to defective nuclear factor kappa B (NF-κB) activation
Autosomal recessive CSR-D due to ICOS-deficiency
CSR-Ds with normal in vitro B-cell responses to CSR activation
Ig CSR-deficiencies with unknown molecular defect(s)
Autosomal recessive mismatch repair deficiency and CSR-D
CSR-D in Ataxia Telangiectasia
Other Ig CSR-deficiencies associated with a DNA repair defect
Conclusion and perspectives
Chapter 17: Unraveling the Complement System and its Mechanism of Action
Abstract
Introduction
Early discovery: heat labile alexin and heat stable antibody
Hemolytic complement
The isolation of complement components
The alternative complement pathway
Complement fragments and regulatory proteins
Mannose-binding proteins
Discovery that complement receptors remove immune complexes
The history of complement-component deficiencies
Animal models of complement deficiency
Lessons learned: the nature of scientific advance
Chapter 18: DiGeorge Syndrome: A Serendipitous Discovery
Abstract
Ancient history
The thymus as an organ of cellular immunity
Additional phenotypic features
The genetic basis OF DiGeorge syndrome
Clinical and laboratory features of DiGeorge syndrome
Treatment of the immune deficiency
Secondary humoral defects in chromosome 22q11.2 deletion syndrome
Summary
Chapter 19: The Many Faces of the Hyper-IgE Syndrome
Abstract
Introduction
Characterization of the disease – phenotypes, inheritance pattern and first linkage analysis: 1966–2004
Discovery of the first two genetic defects – TYK2 and STAT3: 2006 and 2007
Findings of reduced numbers of Th17 cells and diminished Th17 responses in HIES patients: 2008
Discovery of a genetic defect for AR-HIES – DOCK8: 2009
HSCT emerges as a successful therapy for HIES: 1998–2012
Concluding remarks and a glimpse into the future
Acknowledgments
Chapter 20: ADA Deficiency – The First Described Genetic Defect Causing PID
Abstract
Introduction
Hilaire J. Meuwissen
Rochelle Hirschhorn
Michael S. Hershfield
Chapter 21: The Leukocyte Adhesion Deficiency Story
Abstract
Introduction
LAD I
LAD II
LAD III
Chapter 22: How Common Variable Immune Deficiency has Changed Over Six Decades
Abstract
Introduction
Clinical conditions
Treatment
Pathogenesis
Genes and CVID
Conclusion
Chapter 23: From Subcutaneous to Intravenous Immunoglobulin and Back
Abstract
Introduction
Development of human immunoglobulin
Adverse reactions to IVIG and SCIG
Hyperimmune immunoglobulins
Development of therapeutic monoclonal antibodies
A look to the future
Summary
Chapter 24: History of Hematopoietic Stem Cell Transplantation
Abstract
Introduction
The early years
Renewed efforts: focus on animal experiments
The return to clinical transplantation: 1968–1980
Bone marrow transplantation in SCID and Wiskott–Aldrich syndrome
Moving ahead: the 1990s and beyond
Current and future status of HCT for PIDD
Summary
Chapter 25: David’s Story
Abstract
Introduction
Birth and early years
Research studies on David
Immunological studies
Haploidentical T-cell depleted bone marrow transplant
Post-mortem discoveries
David’s immortalized B-cell line: contributions to science
Personal reflections
A mother’s recollection: Carol Ann Demaret
Acknowledgment
Chapter 26: How Primary Immunodeficiencies Have Made Gene Therapy a Reality
Abstract
Introduction
Primary immunodeficiencies
Target cells
Vectors
The first clinical trials of gene therapy
Technical progress
The efficacy of gene therapy for SCID-X1 and ADA deficiency
Genotoxicity
Improvements in vector safety
The latest clinical trials
Conclusion
Index
No. of pages: 376
Language: English
Edition: 1
Published: August 26, 2014
Imprint: Academic Press
Hardback ISBN: 9780124071797
eBook ISBN: 9780124115545
AE
Amos Etzioni
Affiliations and expertise
A. Etzioni, Rambam Medical Center, Department of Pediatrics, Haifa, Israel
HO
Hans D. Ochs
Affiliations and expertise
Professor of Pediatrics, Immunology and Rheumatology, Research Affiliate, Center on Human Development and Disability, University of Washington School of Medicine, Seattle, USA
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