Allergy, immunity and tolerance in early childhood : the first steps of the atopic March

388 Pages·2015·12.17 MB·English

by  Hans Ulrich Wahn

Allergy, Immunity and
Tolerance in Early
Childhood
The First Steps of the Atopic March
Ulrich Wahn
Department of Pediatric Pneumology and
Immunology, Charité University Medicine,
Berlin
Hugh A. Sampson
Icahn School of Medicine at Mount Sinai,
New York
AMSTERDAM • BOSTON • HEIDELBERG • LONDON
NEW YORK • OXFORD • PARIS • SAN DIEGO
SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
Academic Press is an imprint of Elsevier
Academic Press is an imprint of Elsevier
125 London Wall, London EC2Y 5AS, UK
525 B Street, Suite 1800, San Diego, CA 92101-4495, USA
225 Wyman Street, Waltham, MA 02451, USA
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK
Copyright © 2016 Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording, or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment
may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds, or experiments described herein. In using such information
or methods they should be mindful of their own safety and the safety of others, including parties for
whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any
liability for any injury and/or damage to persons or property as a matter of products liability, negligence
or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in
the material herein.
ISBN: 978-0-12-420226-9
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the Library of Congress
For information on all Academic Press publications
visit our website at http://store.elsevier.com/
Publisher: Sara Tenney
Acquisition Editor: Linda Versteeg-Buschman
Editorial Project Manager: Halima Williams
Production Project Manager: Chris Wortley
Designer: Matthew Limbert
Typeset by TNQ Books and Journals
www.tnq.co.in
Printed and bound in the United States of America
List of Contributors
Rob C. Aalberse Department of Immunopathology, Sanquin Blood Supply Foundation
and the Landsteiner Laboratorium, Academic Medical Centre, Amsterdam, The
Netherlands
Birgit Ahrens Department of Pediatric Pneumology and Immunology, Charité
University Medicine, Berlin, Germany
Katrina Allen Food Allergy, School of Inflammation and Repair, University of
Manchester, Murdoch Childrens Research Institute, The Royal Children’s Hospital,
Flemington Road Parkville, Victoria, Australia
Hasan Arshad Allergy & Clinical Immunology, Clinical & Experimental Sciences,
University of Southampton, Southampton, UK; David Hide Asthma and Allergy
Centre, St. Mary’s Hospital, Isle of Wight, UK
Kathleen C. Barnes The Johns Hopkins Asthma & Allergy Center, Baltimore,
MD, USA
Karl E. Bergmann Department of Obstetrics, Charité University Medicine,
Berlin, Germany
Renate Bergmann Department of Obstetrics, Charité University Medicine,
Berlin, Germany
Kirsten Beyer Department of Pediatric Pneumology and Immunology, Charité
University Medicine, Berlin, Germany; Icahn School of Medicine at Mount Sinai,
New York, NY, USA
Bengt Björkstén Institute of Environmental Medicine, Karolinska Institutet, Stock-
holm; School of Health and Medical Sciences, Örebro University, Sweden
Amaziah Coleman Departments of Pediatrics and Medicine, University of Wisconsin-
Madison, Madison, WI, USA
B.C.A.M. van Esch Division of Pharmacology, Utrecht Institute for Pharmaceutical
Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department
of Immunology, Danone Nutricia Research, Utrecht, The Netherlands
xii List of Contributors
J. Garssen Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences,
Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department of
Immunology, Danone Nutricia Research, Utrecht, The Netherlands
James E. Gern Departments of Pediatrics and Medicine, University of Wisconsin-
Madison, Madison, WI, USA
L. Grabenhenrich Institute for Social Medicine, Epidemiology and Health Economics,
Charité University Medicine, Berlin, Germany
Christoph Grüber Department of Pediatrics, Klinikum Frankfurt (Oder), Frankfurt
(Oder), Germany
Peter W. Heymann Division of Pediatric Respiratory Medicine/Allergy, Asthma and
Allergic Diseases Center, University of Virginia, Charlottesville, VA, USA
Patrick Holt Telethon Kids Institute, The University of Western Australia, Perth,
Australia and Queensland Children’s Medical Research Institute, The University of
Queensland, Brisbane, Australia
Kirsi M. Järvinen University of Rochester Medical Center, Pediatric Allergy and
Immunology, Rochester, NY, USA
Maria C. Jenmalm Department of Clinical and Experimental Medicine, Division
of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping
University, Sweden
T. Keil Institute for Social Medicine, Epidemiology and Health Economics, Charité
University Medicine, Berlin, Germany
L.M.J. Knippels Division of Pharmacology, Utrecht Institute for Pharmaceutical
Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department
of Immunology, Danone Nutricia Research, Utrecht, The Netherlands
M.V. Kopp Department of Pediatric Pulmonology, Clinic for Pediatric and Adolescent
Medicine, University Luebeck, Luebeck, Germany
A.I. Kostadinova Division of Pharmacology, Utrecht Institute for Pharmaceutical
Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department
of Immunology, Danone Nutricia Research, Utrecht, The Netherlands
Gideon Lack Clinical Academic Paediatric Allergy Service, Guy’s & St. Thomas’
NHS Foundation Trust, Children’s Allergies Department, St. Thomas’ Hospital,
London, UK
List of Contributors xiii
Susanne Lau Department of Pediatric Pneumology and Immunology, Charité
University Medicine, Berlin, Germany
Karin C. Lødrup Carlsen Department of Paediatrics, Oslo University Hospital,
Oslo, Norway; University of Oslo, Oslo, Norway
Paolo M. Matricardi Department of Pediatric Pneumology and Immunology, Charité
University Medicine, Berlin, Germany
Erika von Mutius Dr. von Hauner Children’s Hospital of Ludwig, Maximilian
University of Munich, Munich, Germany
Martin Penagos Allergy and Clinical Immunology Department, Royal Brompton
Hospital and Imperial College London, London, UK
Petra Ina Pfefferle Comprehensive Biomaterial Bank Marburg CBBM, Centre for
Tumor and Immunobiology, Philipps-University Marburg, Marburg, Germany
Thomas Platts-Mills Asthma and Allergic Disease Center, School of Medicine,
University of Virginia, Charlottesville, VA, USA
Susan L. Prescott School of Paediatrics and Child Health, Telethon KIDS
Institute, University of Western Australia, Princess Margaret Hospital, Perth, WA,
Australia
Harald Renz Institute for Laboratory Medicine and Pathobiochemistry, Molecular
Diagnostics, Philipps-University Marburg, Marburg, Germany
Hugh A. Sampson Icahn School of Medicine at Mount Sinai, New York, NY, USA
Alexandra Santos Department of Paediatric Allergy, Division of Asthma, Allergy and
Lung Biology, King’s College London, Guy’s and St. Thomas’ Hospital NHS
Foundation Trust, London, UK
Bianca Schaub Pediatric Pulmonary Division, University Children’s Hospital
Munich, LMU Munich, Munich, Germany
Jonathan M. Spergel The Children’s Hospital of Philadelphia, Perelman School of
Medicine at University of Pennsylvania, PA, USA
Mimi L.K. Tang Department of Allergy and Immunology, The Royal Children’s
Hospital, Melbourne, VIC, Australia; Allergy and Immune Disorders, Murdoch
Childrens Research Institute, Melbourne, VIC, Australia; Department of Paediatrics,
University of Melbourne, VIC Australia
xiv List of Contributors
Ronald B. Turner Division of Pediatric Infectious Diseases, University of Virginia,
Charlottesville, VA, USA
M.M. Vonk Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences,
Faculty of Science, Utrecht University, Utrecht, The Netherlands; Department of
Immunology, Danone Nutricia Research, Utrecht, The Netherlands
U. Wahn Department of Pediatric Pneumology and Immunology, Charité University
Medicine, Berlin, Germany
John O. Warner Research for the Women and Children’s Clinical Program Group,
Imperial College, London, UK
T. Werfel Department of Dermatology and Allergology, Hannover Medical University,
Hannover, Germany
Magnus Wickman Karolinska Institutet, Institute of Environmental Medicine,
Stockholm, Sweden
L.E.M. Willemsen Division of Pharmacology, Utrecht Institute for Pharmaceutical
Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
Robert A. Wood Johns Hopkins University School of Medicine, Baltimore, MD, USA
Introduction
One understands life only backwards; to live, you must do it forwards.
Søren Aabye Kirkegaard
The term “allergic march” refers to a characteristic sequence of phenotypic changes
of various manifestations in infancy, childhood, and adolescence that seem to be co­
expressed or genetically linked. Despite a wide range of variation in individual pat­
terns of comorbidity, there appears to be a common developmental pattern including:
1. a sequence of individual immunoglobulin E responses starting with cow’s milk and hen’s
egg proteins, followed by indoor and outdoor allergens
2. a sequence of clinical symptoms starting with eczema, which may be followed by rhinitis
and asthma. In most cases, the first atopic manifestations can be observed in early
infancy. The natural history of the disease has been carefully evaluated over the past
two decades by various researchers. They have provided a remarkable gain in knowledge
regarding the earliest changes during pregnancy and their predictive value, the role of
genes, environmental exposure to allergens, microbial products and pollutants, and life­
style and the role of the microbiome.
As it has turned out, atopic diseases have become a major health problem in
childhood in many affluent countries, forcing general pediatricians and primary care
physicians to come to terms with them. The burden of atopic diseases is frequently
dramatic and the cost of health care to deal with this problem in many countries is
highly relevant.
Currently, atopic manifestations represent a challenge for the pediatric allergist,
who is not only responsible for early diagnosis and treatment, but has also a long­
lasting interest in concepts for primary prevention. A number of highly interesting
studies in animal models have led to promising concepts; unfortunately, only a few of
them have been confirmed in humans. In this book, top experts in the field have been
invited to contribute; presenting an update on accumulated knowledge of the natural
history of the disease, as well as hopes and disappointments surrounding allergen­
specific or nonspecific early interventions, including studies of microbial products.
Not least in its achievement, this book outlines gaps in knowledge and presents novel
hypotheses that might stimulate research and patient care in years to come.
Ulrich Wahn
Hugh Sampson
The Maturation of Immune 1
Function in Pregnancy and Early
Childhood
Bianca Schaub*, Susan L. Prescott§
*Pediatric Pulmonary Division, University Children’s Hospital Munich, LMU Munich,
Munich, Germany; §School of Paediatrics and Child Health, Telethon KIDS Institute,
University of Western Australia, Princess Margaret Hospital, Perth, WA, Australia
Introduction
“The first 1000 days” has become a core focus and a prominent catch phrase in grow-
ing efforts to understand the developmental programming of disease predisposition
in early life. Spanning all aspects of health, the strong concept of the developmental
origins of health and disease is based on clear evidence that events and exposures in
early development can have lasting and sometimes latent effects on later health.1,2
Although the early focus of this research was on later-onset cardiometabolic diseases,
it is clear that earlier-onset noncommunicable diseases (NCDs) such as allergic dis-
eases share similar risk factors and should be regarded as a core part of this agenda.3
Understanding the early environmental influences on early immune development is
also a key element in disease prevention.
The immune system has a critical role in the development, homeostasis, and
function of virtually all organ systems. Subtle early variations in the pattern of
immune response can predispose to disease and influence both the propensity and
the dynamics of inflammation in later life.4 The modern epidemic of infant allergic
disease has drawn considerable attention to the importance of early immune devel-
opment and the potential impact of modern environmental changes on the maturing
immune system. In addition to its obvious role in the rising predisposition to allergic
and autoimmune disease, early immune dysregulation is now implicated in a range
of NCDs, including predisposition to mental health disorders and cardiovascular
disease.3,5 With economic prosperity and lifestyle changes, the rising propensity
for inflammation is implicated in the rising burden of chronic disease and all-cause
mortality in modern societies. It is therefore critically important to understand the
normal processes and pathways that underpin the normal immune development, how
these are modified by adverse early environmental exposures to lead to disease,
and how these may be favorably modified to reduce that risk. Optimizing immune
health in early life will reduce the risk of allergy and immune diseases, but it is also
likely to reduce the burden of many other chronic inflammatory diseases. Because
immune function is so responsive to the early environment, and because immune
Allergy, Immunity and Tolerance in Early Childhood. http://dx.doi.org/10.1016/B978-0-12-420226-9.00001-2
Copyright © 2016 Elsevier Inc. All rights reserved.
2 Allergy, Immunity and Tolerance in Early Childhood
disease manifests so early, this provides an important early indicator for the effects
of environment on human health.
Immune development in health and disease
Healthy immune maturation depends on efficient communication between the two pil-
lars of immune regulation, the innate and adaptive immune systems, which are com-
posed of a large number of involved cells (details are given in Ref. 6).
In brief, innate immune cells such as monocytes, granulocytes, dendritic cells (DC),
natural killer (NK) cells, mast cells, thrombocytes, and locally relevant cells (e.g., pul-
monary alveolar macrophages) are present during healthy immune maturation and are
mostly active in some allergy-affected organs such as, for example, the skin and the
respiratory tract.7
In addition, innate lymphoid type 2 cells, NK2 subsets, and regulatory NK and
NK22 cells were shown to be involved in functional T cell responses, the production of
immunoglobulin E (IgE), and the function of the epithelial cell barrier, are thus possibly
involved in allergy development.8,9 Also, precursors of innate bone marrow-derived
mucosal DC and the NLRP3 inflammasome may be involved in either inflammatory
signaling cascades after virus infections or airway inflammation,10 both of which are
relevant for allergy development.
In close connection with innate immunity, the key players of adaptive immune
regulation, namely different T cell subpopulations composed of Th2, Th1, and T but
reg
also Th17, Th9, and Th22, and CD8+ cells, B cells, and regulatory B cells, are critical
for healthy immune maturation and thus protection against allergic diseases.7
Early life immune regulation
The prenatal period is instrumental in shaping a child’s immune system (“program-
ming”) influenced by a wide variety of factors elucidated below, including microbi-
ome, nutrition, smoke exposure, and infection, among many others (Figure 1). This
window of opportunity is thus critical for a wide range of risk and protective influences
discussed in more detail below. Multifaceted effects on early immune programming
can occur prenatally that are critical for effects on local tissues and relevant for risk
for or protection from immune-mediated diseases, which may occur only several years
later. Thus, an efficient interplay between innate and adaptive immune regulation can
shape the maturing immune system, keeping it balanced over numerous years during
childhood. Any default regulation affecting solely parts of the system or even cells
can result in different immune-mediated diseases such as infections, more chronic
diseases such as, for example, allergies, autoimmune diseases, or lack of tolerance.
Whereas bidirectional interactions between the fetus and mother seem critical for
postnatal immune regulation, human studies on causal effects are complex because of
multifaceted influences that are difficult to study at this time of maturation.
In addition to genetic factors such as “immutable footprints”, epigenetics, the envi-
ronment, and their interactions influence early immune programming, subsequently
Early Childhood Immune Maturation 3
Figure 1 Influences on prenatal and postnatal immune programming for the devel-
opment of allergic diseases. A wide range of environmental factors acting prenatally and/or
postnatally are known to influence the maturation of immunological competence combined with
genotype and epigenetics, and hence to modulate the risk for the development of allergic diseases.
Reproduced with permission from Holt, Sly, Prescott, 2011. Early life origins of allergy and
asthma (Figure 3). In: Stephen T., Holgate, Martin K., Church, David H., Broide, Fernando, D.
(Eds.), Allergy: Principles and Practice, fourth ed. Elsevier Inc., Martinez.
affecting anatomical structures such as the mucosa and epithelium, and influencing
barrier function.
The exact nature underpinning intrauterine modulatory mechanisms may be
composed of the following: Although the amniotic fluid has been shown not to
be sterile, direct and indirect modulation via fetoplacental transfer may occur.
Decidual tissue maternal immune cells including macrophages, CD8+ and γδ-T
cells, and large granulated lymphocyte cells are able to induce rejection of pater-
nal histocompatibility antigens. Maternal–fetal tolerance to paternal alloantigens
is actively mediated, involving pT (peripheral T ) distinctly responding to
regs regs
paternal antigens for tolerance induction.11 Generally, maturation of the infant
adaptive immune system occurs from the 15th to 20th week of gestation and can
be Ag-specific.
Postnatal immune maturation influences are comparable to before birth, with the
major difference in the absence of direct maternal environment. Whereas effects on
immune programming most likely happen continuously with different thresholds
on several types of immune cells, numerous factors induce changes directly in the
organs subsequently affected by later disease. For allergic diseases, for example,