Primary Immunodeficiency Disorders A Historic and Scientific Perspective 1st Edition by Amos Etzioni, Hans D Ochs ISBN 9780124071797 0124071791

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

CSR-Ds caused by an intrinsic B-cell defect

Autosomal recessive activation-induced cytidine deaminase deficiency

Uracil-N glycosylase (UNG) deficiency

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