Clinical Immunology: Principles and Practice

1357 Pages·2018·210.7 MB·English

by  Robert Rich

CHAPTER i
Clinical Immunology:
Principles and Practice
FIFTH EDITION
ROBERT R. RICH MD
Professor of Medicine and Dean Emeritus, University of Alabama at Birmingham, Birmingham, AL, USA
THOMAS A. FLEISHER MD
Executive Vice President, American Academy of Allergy, Asthma and Immunology, Milwaukee, WI; Scientist Emeritus, NIH Clinical
Center, National Institutes of Health, Bethesda, MD, USA
WILLIAM T. SHEARER MD, PhD
Allergy and Immunology Service, Texas Children’s Hospital, Professor of Pediatrics and Immunology, Section of Allergy and
Immunology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
HARRY W. SCHROEDER, JR. MD, PhD
Professor of Medicine, Microbiology, and Genetics, Division of Clinical Immunology and Rheumatology, Director, UAB Program in
Immunology, University of Alabama at Birmingham, Birmingham, AL, USA
ANTHONY J. FREW MD, FRCP
Professor of Allergy and Respiratory Medicine, Department of Respiratory Medicine, Royal Sussex County Hospital, Brighton, UK
CORNELIA M. WEYAND MD, PhD
Professor of Medicine, Stanford University, Stanford, CA, USA
For additional online content visit ExpertConsult.com
© 2019, Elsevier Limited. All rights reserved.
First edition 1996
Second edition 2001
Third edition 2008
Fourth edition 2013
Fifth edition 2019
The right of Robert R. Rich, Thomas A. Fleisher, William T. Shearer, Harry W. Schroeder Jr., Anthony J. Frew,
Cornelia M. Weyand to be identified as authors of this work has been asserted by them in accordance with the
Copyright, Designs and Patents Act 1988.
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This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Chapter 9, Cytokines and cytokine receptors is in the public domain.
Chapter 79, Lymphomas; Elaine S. Jaffe and Stefania Pittaluga contributions are the public domain.
Chapter 88, Protein kinase antagonists as therapeutic agents for immunological and inflammatory disorders;
John J. O’Shea and Massimo Gadina contributions are in the public domain.
Chapter 92, Flow Cytometry is in the public domain.
Notices
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds or experiments described herein. Because of rapid advances
in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be
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vi Preface to the first edition
P R E FAC E TO T H E F I R S T E D I T I O N
Clinical immunology is a discipline with a distinguished history, treatment of immunologic deficiency syndromes. Pathogenic
rooted in the prevention and treatment of infectious diseases in mechanisms of both congenital and acquired immune deficiency
the late nineteenth and early twentieth centuries. The conquest diseases are discussed, as are the infectious complications that
of historical scourges such as smallpox and (substantially) polio characterize these diseases. Befitting its importance, the subject of
and relegation of several other diseases to the category of medical HIV infection and AIDS receives particular attention, with separate
curiosities is often regarded as the most important achievement chapters on the problem of infection in the immunocompromised
of medical science of the past fifty years. Nevertheless, the chal- host, HIV infection in children, anti-retroviral therapy and current
lenges facing immunologists in the efforts to control infectious progress in the development of HIV vaccines.
diseases remain formidable; HIV infection, malaria and tuber- The classic allergic diseases are the most common immunologic
culosis are but three examples of diseases of global import that diseases in the population, ranging from atopic disease to drug
elude control despite major commitments of monetary and allergy to organ-specific allergic disease (e.g., of the lungs, eye
intellectual resources. and skin). They constitute a foundation for the practice of clinical
Although firmly grounded in the study and application of immunology, particularly for those physicians with a practice
defenses to microbial infection, since the 1960s clinical immunol- orientation defined by formal subspecialty training in allergy
ogy has emerged as a far broader discipline. Dysfunction of the and immunology. A major section is consequently devoted to
immune system has been increasingly recognized as a pathogenic these diseases, with an emphasis on pathophysiology as the basis
mechanism that can lead to an array of specific diseases and for rational management.
failure of virtually every organ system. Pardoxically, although The next two sections deal separately with systemic and
the importance of the immune system in disease pathogenesis organ-specific immunologic diseases. The diseases considered
is generally appreciated, the place of clinical immunology as a in the first of these sections are generally regarded as the core
practice discipline has been less clear. As most of the noninfectious practice of the clinical immunologist with subdisciplinary
diseases if the human immune system lead eventually to failure emphasis in rheumatology. The second section considers diseases
of other organs, it has been organ-specific subspecialists who of specific organ failure as consequences of immunologically
have usually dealt with their consequences. Recently, however, mediated processes that may involve virtually any organ system.
the outlook has begun to change as new diagnostic tools increas- These diseases include as typical examples the demyelinating
ingly allow the theoretical possibility of intervention much earlier diseases, insulin-dependent diabetes mellitus, the glomerulone-
in disease processes, often before irreversible target organ phritides and inflammatory bowel diseases. It is in management
destruction occurs. More importantly, this theoretical possibility of such diseases that the discipline of clinical immunology will
is increasingly realized as clinical immunologists find themselves have an increasing role as efforts focus on intervention early in
in the vanguard of translating molecular medicine from laboratory the pathogenic process and involve diagnostic and therapeutic
bench to patient bedside. tools of ever-increasing sophistication.
In many settings, clinical immunologists today function as One of the major clinical areas in which the expertise of a
primary care physicians in the management of patients with clinical immunologist is most frequently sought is that of
inmune-deficiency, allergic, and autoimmune diseases. Indeed allogeneic organ transplantation. A full section is devoted to the
many influential voices in the clinical disciplines of allergy and issue of transplantation of solid organs, with an introductory
rheumatology support increasing coalescence of these traditional chapter on general principles of transplantation and management
subspecialities around their intellectual core of immunology. In of transplantation rejection followed by separate chapters dealing
addition to his or her role as a primary care physician, the clinical with the special problems of transplantation of specific organs
immunologist is increasingly being looked to as a consultant, as or organ systems.
scientific and clinical advances enhance his or her expertise. The Appreciation of both the molecular and clinical features of
immunologist with a ‘generalist’ perspective can be particularly lymphoid malignancies is important to the clinical immunologist
helpful in the application of unifying principles of diagnosis and regardless of subspecialty background, notwithstanding the fact
treatment across the broad spectrum of immunologic diseases. that primary responsibility for management of such patients
Clinical Immunology: Principles and Practice has emerged will generally fall to the haematologist/oncologist. A separate
from this concept of the clinical immunologist as both primary section is consequently devoted to the lymphocytic leukemias and
care physician and expert consultant in the management of lymphomas that constitute the majority of malignancies seen in
patients with immunologic diseases. It opens in full appreciation the context of a clinical immunology practice. The separate issues
of the critical role of fundamental immunology in this rapidly of immune responses to tumors and immunological strategies to
evolving clinical discipline. Authors of basic science chapters treatment of malignant diseases are subjects of additional chapters.
were asked, however, to cast their subjects in a context of clinical Another important feature is the attention to therapy of
relevance. We believe the result is a well-balanced exposition of immunologic diseases. This theme is constant throughout the
basic immunology for the clinician. chapters on the allergic and immunologic diseases, and because
The initial two sections on basic principles of immunology of the importance the editors attach to clinical immunology
are followed by two sections that focus in detail on the role of as a therapeutic discipline, an extensive section is also devoted
the immune system in defenses against infectious organisms. The specifically to this subject. Subsections are devoted to issues of
approach is two-pronged. It begins first with a systematic survey immunologic reconstitution, with three chapters on treatment
of immune responses to pathogenic agents followed by a detailed of immunodeficiences, malignancies and metabolic diseases by
vi
Preface to the first edition vii
bonemarrow transplantation. Also included is a series of chapters In summary, we have intended to provide the reader with a
on pharmaceutical agents currently available to clinical immunolo- comprehensive and authoritative treatise on the broad subject
gists, both as anti-allergic and anti-inflammatory drugs, as well as of clinical immunology, with particular emphasis on the diagnosis
newer agents with greater specificity for T cell-mediated immune and treatment of immunological diseases. It is anticipated that
responses. The section concludes with a series of chapters that the book will be used most frequently by the physician specialist
address established and potential applications of therapeutic practicing clinical immunology, both in his or her role as a
agents and approaches that are largely based on the new techniques primary physician and as a subsequent consultant. It is hoped,
of molecular medicine. In addition to pharmaceutical agents the however, that the book will also be of considerable utility to the
section deals in detail with such subjects as apheresis, cytokines, non-immunologist. Many of the diseases discussed authoritatively
monoclonal antibodies and immunotoxins, gene therapy and in the book are diseases commonly encountered by the generalist
new experimental approaches to the treatment of autoimmunity. physician. Indeed, as noted, because clinical immunology involves
The book concludes with a section devoted to approaches and diseases of virtually all organ systems, competence in the diagnosis
specific techniques involved in the diagnosis of immunologic and management of immunological diseases is important to
diseases. Use of the diagnostic laboratory in evaluation of complex virtually all clinicians. The editors would be particularly pleased
problems of immunopathogenesis has been a hallmark of the to see the book among the references readily available to the
clinical immunologist since inception of the discipline and practicing internist, pediatrician and family physician.
many clinical immunologists serve as directors of diagnostic
immunology laboratories. Critical assessment of the utilization of Robert R. Rich
techniques ranging from lymphocyte cloning to flow cytomeric Thomas A. Fleisher
phenotyping to molecular diagnostics are certain to continue as Benjamin D. Schwartz
an important function of the clinical immunologist, particularly William T. Shearer
in his or her role as expert consultant. Warren Strober
viii Part one Principles of Immune Response
P R E FAC E TO T H E F I F T H E D I T I O N
Each edition of Clinical Immunology: Principles and Practice has reminiscent of that served by infectious disease physicians,
documented important changes in the discipline from the preced- particularly during the era of antibiotic proliferation in the last
ing one. This fifth edition is emphatically not an exception to quarter of the previous century. It is consequently our hope that
that pattern. Indeed, advances in both the Principles and Practice the book will find a place near the desk of most persons whose
of clinical immunology have been remarkable. The constant practice relies on the science or practice of clinical immunology
theme of every edition has been to emphasize that our discipline as we have broadly defined it. We further trust that it will be
touches virtually all organ systems. The diseases that are covered especially useful to trainees and practitioners preparing for
range from too little to too much immunity; and from dysregu- certification or recertification in an immunology-related sub-
lated, malignant or replaced immunological systems and functions. specialty. In an effort to assist the latter group and as an aid to
Fundamental concepts that are essential to a precise understanding continuing education of all readers, we have added to the online
of normal and disordered immune function and disease patho- version of the text, which all purchasers of the book can readily
genesis are again balanced by clinical descriptions, diagnostic access, multiple choice questions relevant to every chapter.
approaches and therapeutic options. Additionally, we continue to believe that a comprehensive text
Several examples of particularly notable advances are worth on clinical immunology can be a valuable asset for generalists
highlighting: Our increasing appreciation of the importance of in any specialty, particularly internists, pediatricians and family
the microbiota to normal immune system development and to physicians, who regularly care for patients across the broad
the pathogenesis of immunologic and inflammatory diseases; spectrum of immunological disorders, offering an opportunity
dissection of relationships between the innate and adaptive for physicians in all disciplines to upgrade their skills and educa-
immune systems that has served to further clarify the expres- tion, and to benefit from the onward rush of science and practice
sion of inflammatory processes and their interaction in defenses improvement in modern clinical immunology.
against infectious agents; progress in rapid and cost-effective The book continues features that have been well received in
genomics that has led to the definition of numerous new primary previous editions. Chapters are generously illustrated and all
immune deficiencies and provided new insights into the genetic chapters contain summary Boxes (commonly in bulleted form)
aspects of many other immunologic diseases; understanding of that provide Key Concepts and a Box labeled as On the Horizon,
immune deficiencies that reflect development of anti-cytokine in which authors look to research opportunities for important
auto-antibodies; detailed definition of cell signaling pathways advances over the next 5-10 years. Furthermore, due to the
and the structure of cell-surface molecules that have contributed extraordinarily cross-disciplinary nature of clinical immunology,
enormously to the treatment of cancer and autoimmunity with it is our hope that investigators working in one area might find
a virtual explosion in novel therapeutics including check-point new ideas and opportunities in the On the Horizon Boxes outside
inhibitors and other recently developed immunomodulators; their primary area of focus. Other Boxes similarly summarize
availability of many new humanized and human monoclonal content with Clinical Relevance, Clinical Pearls, and Therapeutic
antibodies and development of novel therapeutic approaches Principles.
such as chimeric-antigen-receptor T cells; wide use of T cell As always, we are immensely grateful to the hundreds of
excision circle receptor (TREC) assay to diagnose serious immune physicians and scientists whose contributions are the essence of
deficiencies of the newborn; and exploration of in vivo therapeutic the book. Finally, we recognize the diligence and commitment
editing of pathological mutations. With these new tools the of our colleagues at Elsevier who have supported all aspects of
practice of clinical immunology has become more interesting the book’s development and production, particularly Ms. Joanne
yet more complex, while offering important improvements in Scott who has worked with both authors and editors from concept
patient care. to birth to completion of every chapter.
Our goal with this edition is to enhance the interest of
practitioners in the many specialties and subspecialties that the Robert R. Rich
discipline impacts and to assist them in understanding this Thomas A. Fleisher
increasing complexity. With the increasing availability of powerful William T. Shearer
new therapeutic agents, the expert clinical immunologist today Harry W. Schroeder, Jr.
may function as a primary care physician or consultant in the Anthony J. Frew
management of patients with immune deficiencies, allergic, and Cornelia M. Weyand
autoimmune diseases involving multiple organ systems – a role
viii
LIST OF CONTRIBUTORS ix
L I S T O F C O N T R I B U TO R S
The editor(s) would like to acknowledge and offer grateful thanks for the input of all previous editions’ contributors, without whom
this new edition would not have been possible.
Roshini Sarah Abraham PhD, D(ABMLI) Howard A. Austin III MD Tapan Bhavsar MD, PhD
Consultant Senior Clinical Investigator Clinical Fellow in Hematopathology
Department of Laboratory Medicine and National Institute of Diabetes and National Cancer Institute/National
Pathology Digestive and Kidney Diseases Institute of Health
Mayo Clinic National Institutes of Health, Bethesda, Bethesda, MD, USA
Rochester, MN, USA MD, USA
Professor of Medicine, Professor of J. Andrew Bird MD
Laboratory Medicine and Pathology Subash Babu MBBS, PhD Associate Professor
Scientific Director Department of Pediatrics
Cristina Albanesi BSc, PhD NIH-NIRT-International Center for Division of Allergy and Immunology
Senior Investigator Excellence in Research University of Texas Southwestern Medical
Laboratory of Experimental Immunology National Institute for Research in Center in Dallas
Fondazione “Luigi Maria Monti” Tuberculosis Dallas, TX, USA
(FLMM)—Istituto Dermopatico Chennai, India
dell’Immacolata (IDI)-IRCCS Sarah E. Blutt PhD
Rome, Italy Mark C. Ballow MD Assistant Professor
Professor, Department of Pediatrics Department of Molecular Virology and
Ilias Alevizos DMD, MMSc Division of Allergy, Immunology and Microbiology and Department of
Assistant Clinical Investigator Pediatric Rheumatology Molecular and Cellular Biology
National Institute of Dental and Women and Children’s Hospital of Buffalo Baylor College of Medicine
Craniofacial Research State University of New York at Buffalo Houston, TX, USA
National Institutes of Health School of Medicine and Biomedical
Bethesda, MD, USA Sciences Mark Boguniewicz MD
Buffalo, NY, USA Professor, Division of Pediatric
Juan Anguita PhD Allergy-Immunology
Ikerbasque Professor James E. Balow MD National Jewish Health
CIC bioGUNE Clinical Director and Chief Denver, CO, USA
Derio, Bizkaia, Spain Kidney Disease Section
National Institute of Diabetes and Rafael Bonamichi-Santos, MD
Brendan Antiochos MD Digestive and Kidney Diseases Division of Clinical Immunology and
Instructor National Institutes of Health Allergy Division
Division of Rheumatology Bethesda, MD, USA University of São Paulo
Johns Hopkins University School of São Paulo, SP, Brazil
Medicine John W. Belmont MD, PhD
Baltimore, MD, USA Professor Bertrand Boisson PhD
Department of Molecular and Human Laboratory of Human Genetics of
Cynthia Aranow, MD Genetics Infectious Diseases
Investigator, Clinical Research Baylor College of Medicine Necker Branch, Imagine Institute;
Autoimmune and Musculoskeletal Houston, TX, USA Paris Descartes University, France;
Diseases St. Giles Laboratory of Human Genetics of
The Feinstein Institute for Medical Claudia Berek PhD Infectious Diseases, Rockefeller Branch
Research Group Leader, B Cell Immunology The Rockefeller University
Manhasset, NY, USA Deutsches Rheuma-Forschungszentrum New York, NY, USA
Berlin (DRFZ)
John P. Atkinson, MD Berlin, Germany Elena Borzova MD, PhD
Department of Medicine Professor of Clinical Allergy
Chief, Division of Rheumatology Timothy Beukelman MD, MSCE Department of Clinical Allergology
Samuel B. Grant Professor of Medicine Associate Professor of Pediatric Russian Medical Academy of Postgraduate
Professor of Molecular Microbiology Rheumatology Education
Washington University School of Medicine Division of Rheumatology Moscow, Russian Federation
St. Louis, MO, USA The University of Alabama at Birmingham
Birmingham, AL, USA
ix
x LIST OF CONTRIBUTORS
Prosper N. Boyaka PhD Matthew Campbell, MD, MS David D. Chaplin, MD, PhD
Professor Assistant Professor Professor of Microbiology and Medicine
Department of Veterinary Biosciences Department of Genitourinary Medical University of Alabama at Birmingham
The Ohio State University Oncology Birmingham, AL
College of Veterinary Medicine Division of Cancer Medicine
Columbus, OH, USA The University of Texas MD Anderson W. Winn Chatham MD
Cancer Center Professor of Medicine
Joshua Boyce MD Houston, TX, USA Louis W. Heck Clinical Scholar
Professor of Medicine and Pediatrics Clinical Director, Division of Clinical
Director, Inflammation and Allergic Adela Rambi G. Cardones, MD Immunology and Rheumatology
Disease Research Section Assistant Professor University of Alabama at Birmingham
Director, Jeff and Penny Vinik Center for Department of Dermatology Birmingham, AL, USA
Allergic Disease Research Duke University School of Medicine
Harvard Medical School, Brigham and Durham, NC Edward S. Chen, MD
Women’s Hospital Assistant Professor
Boston, MA, USA Jean-Laurent Casanova MD, PhD Division of Pulmonary and Critical Care
Director Medicine
Sarah K. Browne St Giles Laboratory of Human Genetics of Johns Hopkins University School of
Office of Vaccine Research and Review Infectious Diseases Medicine
Center for Biologics Evaluation and Rockefeller Branch, The Rockefeller Baltimore, MD USA
Research University
Food and Drug Administration Howard Hughes Medical Institute Javier Chinen MD, PhD
Silver Spring, MD, USA New York, NY, USA; Assistant Professor
Co-Director Departments of Pediatrics
Wesley Burks MD Laboratory of Human Genetics of Baylor College of Medicine
Curnen Distinguished Professor Infectious Diseases Houston, TX, USA
Executive Dean Necker Branch, Imagine Institute
School of Medicine Paris Descartes University Lisa Christopher-Stine MD, MPH
The University of North Carolina Paris Sorbonne Cité; Assistant Professor of Medicine
Chapel Hill, NC, USA Professor of Pediatrics Director
Pediatric Hematology-Immunology Unit John Hopkins Myositis Center
Jacinta Bustamante MD, PhD Necker Hospital, Assistance Publique Johns Hopkins University Bloomberg
Research Associate Hôpitaux de Paris School of Public Health
Laboratory of Human Genetics of Paris, France Baltimore, MD, USA
Infectious Diseases
Necker Branch, Imagine Institute Mariana Castells MD, PhD Michael Ciancanelli PhD
Paris Descartes University Director, Drug Hypersensitivity and Research Associate
Paris Sorbonne Cité Desensitization Center St Giles Laboratory of Human Genetics of
Associate Professor of Cellular Biology Director, Allergy Immunology Training Infectious Diseases
Study Center for Primary Program Rockefeller Branch
Immunodeficiencies Associate Director Mastocytosis Center The Rockefeller University
Necker Hospital, Assistance Publique Brigham and Women’s Hospital New York, NY, USA
Hôpitaux de Paris Harvard Medical School
Paris, France Boston, MA, USA Andrew P. Cope BSc, PhD, MBBS, FRCP,
St. Giles Laboratory of Human Genetics FHEA
of Infectious Diseases, Rockefeller Lisa A. Cavacini PhD Head, Academic Department of
Branch Associate Professor Rheumatology
The Rockefeller University Department of Medicine Centre for Molecular and Cellular Biology
New York, NY, USA University of Massachusetts Medical of Inflammation
School Division of Immunology, Infection and
Virginia L. Calder PhD MassBiologics Inflammatory Disease
Senior Lecturer in Immunology Boston, MA, USA King’s College School of Medicine
Department of Molecular Therapy and King’s College London
Genetics Edwin S.L. Chan MD, FRCPC London, UK
UCL Institute of Ophthalmology Assistant Professor Arthritis Research UK Professor of
London, UK Department of Medicine Rheumatology
New York University School of Medicine
New York, NY, USA David B. Corry MD
Professor
Departments of Medicine, Pathology and
Immunology
Baylor College of Medicine
Houston, TX, USA
LIST OF CONTRIBUTORS xi
Filippo Crea MD, FESC, FACC Stéphanie Dupuis-Boisson PhD Thomas A. Fleisher MD
Full Professor Research Associate Executive Vice President
Department of Cardiology Laboratory of Human Genetics of American Academy of Allergy, Asthma
Catholic University of Sacred Heart Infectious Diseases and Immunology
Rome, Italy Necker Branch, Imagine Institute Milwaukee, WI, USA
Paris Descartes University Scientist Emeritus
Randy Q. Cron MD, PhD Paris Sorbonne Cité, Paris, France; NIH Clinical Center
Professor of Pediatrics and Medicine St Giles Laboratory of Human Genetics of National Institutes of Health
Children’s Hospital of Alabama Infectious Diseases Bethesda, MD, USA
University of Alabama at Birmingham Rockefeller Branch
Birmingham, AL, USA The Rockefeller University Luz Fonacier MD
New York, NY, USA Section of Allergy and Immunology
Jennifer M. Cuellar-Rodriguez MD NYU Winthrop Hospital
Staff Clinician Todd N. Eagar PhD Mineola, NY, USA
Laboratory of Clinical Infectious Assistant Professor
Diseases Department of Pathology and Genomic Andrew P. Fontenot MD
National Institute of Allergy and Medicine Henry N. Claman Professor of Medicine
Infectious Diseases Houston Methodist Hospital Division Head, Allergy and Clinical
National Institutes of Health Houston, TX, USA Immunology
Bethesda, MD, USA Department of Medicine
Craig A. Elmets MD University of Colorado Anschutz Medical
Marinos C. Dalakas MD, FAAN Director, UAB Skin Diseases Research Campus
Professor of Neurology Center Aurora, CO, USA
Director, Neuromuscular Division University of Alabama at Birmingham
Thomas Jefferson University Philadelphia Birmingham, AL, USA Alexandra F. Freeman MD
PA and Professor and Chair, Department of Staff Clinician
Chief, Neuroimmunology Unit, Dermatology Laboratory of Clinical Infectious
Department of Pathophysiology Diseases
National and Kapodistrian University of Doruk Erkan MD National Institute of Allergy and Infectious
Athens Medical School Associate Physician-Scientist Diseases
Athens, Greece Barbara Volcker Center for Women and National Institutes of Health
Rheumatic Disease Bethesda, MD, USA
Sara M. Dann PhD New York, NY, USA;
Assistant Professor Associate Professor of Medicine Anthony J. Frew MD, FRCP
Departments of Internal Medicine, and Weill Cornell Medical College Professor of Allergy and Respiratory
Microbiology and Immunology Associate Attending Rheumatologist, Medicine
University of Texas Medical Branch Hospital for Special Surgery Department of Respiratory Medicine
Galveston, TX, USA New York, NY, USA Royal Sussex County Hospital
Brighton, UK
Betty Diamond MD Laura Fanning, MD
Professor Instructor of Medicine Kohtaro Fujihashi DDS, PhD
Department of Microbiology and Harvard Medical School, Brigham and Professor, Department of Pediatric
Immunology and Medicine (AECOM) Women’s Hospital Dentistry
The Feinstein Institute for Medical Research Boston, MA, USA Immunobiology Vaccine Center
Director The Institute for Oral Health Research,
Laboratory of Autoimmune Diseases and Erol Fikrig MD School of Dentistry
Musculoskeletal Disorders Section Chief, Division of Infectious The University of Alabama at Birmingham
Head, Center for Autoimmune Diseases and Diseases Birmingham, AL, USA
Musculoskeletal Disorders Yale University
Manhasset, NY, USA Investigator, Howard Hughes Medical Massimo Gadina PhD
Institute Director
Terry W. Du Clos MD, PhD Professor of Epidemiology (Microbial Office of Science and Technology
Professor of Medicine Diseases) and Microbial Pathogenesis National Institute of Arthritis
School of Medicine Waldemar Von Zedtwitz Professor of Musculoskeletal and Skin Diseases
University of New Mexico; Medicine (Infectious Diseases) National Institutes of Health
Head of Rheumatology New Haven, CT, USA Bethesda, MD, USA
VA Medical Center
Albuquerque, NM, USA Davide Flego, PhD Moshe E. Gatt MD
Catholic University of the Sacred Heart Resident, Department of Hematology
UNICATT Hadassah-Hebrew University Medical
Institute of Cardiology Center
Milan, Italy Jerusalem, Israel
xii LIST OF CONTRIBUTORS
M. Eric Gershwin MD Robert G. Hamilton PhD, D(ABMLI) Dennis Hourcade, PhD
Chief, Division of Rheumatology Professor of Medicine and Pathology Professor of Medicine
Allergy and Clinical Immunology Johns Hopkins University School of Washington University
University of California Davis Health System Medicine and School of Medicine
Distinguished Professor of Medicine, Jack Director St. Louis, MO, USA
and Donald Chi Professor of Medicine Johns Hopkins Dermatology, Allergy and
Davis, CA, USA Clinical Immunology Reference Nicholas D. Huntington PhD
Laboratory Molecular Immunology Division
Susan L. Gillespie MD, PhD Johns Hopkins University School of The Walter and Eliza Hall Institute of
Associate Professor of Pediatrics Medicine Medical Research;
Baylor College of Medicine Baltimore, MD, USA Department of Medical Biology
Baylor International Pediatric AIDS University of Melbourne
Initiative (BIPAI) Laurie E. Harrington, PhD Parkville, Victoria, Australia
Texas Children’s Health Center for Associate Professor
International Adoption Department of Cell, Developmental and Tracy Hwangpo MD, PhD
Houston, TX, USA Integrative Biology Instructor
University of Alabama at Birmingham Division of Clinical Immunology and
Jörg J. Goronzy MD, PhD Birmingham, AL, USA Rheumatology, Department of Medicine
Professor of Medicine University of Alabama at Birmingham
Stanford University School of Medicine Leonard C. Harrison MD DSc, DMedSci School of Medicine
Stanford, CA, USA (hon. causa), FRACP, FRCPA, FAHMS Birmingham, AL, USA
Professor, NHMRC Senior Principal
Sangeeta Goswami, MD, PhD Research Fellow John B. Imboden MD
Clinical Specialist Population Health and Immunity Alice Betts Endowed Chair for Research in
Research Instructor, Department of Division Arthritis
Genitourinary Medical Oncology The Walter and Eliza Hall Institute of Professor of Medicine
Research, Division of Cancer Medicine Medical Research University of California
The University of Texas MD Anderson Victoria, Australia San Francisco, CA, USA
Cancer Center
Houston, TX, USA Sarfaraz A. Hasni MD Fadi Issa D.Phil. BM BCh,
Lawrence Schulman Clinical Research Academic Clinical Lecturer
Clive E.H. Grattan MD, FRCP Scholar Nuffield Department of Surgical Sciences,
Consultant Dermatologist National Institute of Arthritis, University of Oxford
Dermatology Centre Musculoskeletal and Skin Diseases Oxford, UK
Norfolk and Norwich University Hospital National Institutes for Health
Norwich, UK Bethesda, MD, USA Shai Izraeli MD
Associate Professor of Pediatrics
Neil S. Greenspan MD, PhD Arthur Helbling MD Department of Pediatric Hemato-Oncology
Professor of Pathology Associate Professor of Allergology and Edmond and Lily Safra Children Hospital
Case Western Reserve University Clinical Immunology Sheba Medical Center and University of
Cleveland, OH, USA Division of Allergology Tel-Aviv School of Medicine
University Clinic for Rheumatology, Tel-Aviv, Israel
Sarthak Gupta, MD Immunology and Allergology (RIA)
Systemic Autoimmunity Branch Inselspital Elaine S. Jaffe MD
National Institute of Arthritis and Bern, Switzerland Head, Hematopathology
Musculoskeletal and Skin Diseases Laboratory of Pathology
National Institutes of Health Joanna Hester PhD Center for Cancer Research
Bethesda, MD, USA Kidney Research UK Senior Fellow National Cancer Institute
Nuffield Department of Surgical Sciences Bethesda, MD, USA
Claire E. Gustafson, PhD University of Oxford
Division of Immunology and Oxford, UK Sirpa Jalkanen MD, PhD
Rheumatology Academy Professor
Department of Medicine Steven M. Holland MD Center of Excellence
Stanford University Chief, Immunopathogenesis Section; University of Turku
Stanford, CA, USA Tenured Investigator Turku, Finland
National Institute of Allergy and
Russell P. Hall III MD Infectious Diseases Stacie Jones MD
J. Lamar Callaway Professor and Chair National Institutes of Health Division of Allergy/Immunology,
Department of Dermatology Bethesda, MD, USA Department of PediatricsUniversity of
Duke University School of Medicine Chief, Laboratory of Clinical Infectious Arkansas for Medical Sciences and
Durham, NC, USA Diseases Arkansas Children’s Hospital
Little Rock, AR, USA