ebook img

Molecular Allergy Diagnostics: Innovation for a Better Patient Management PDF

537 Pages·2017·13.25 MB·English
Save to my drive
Quick download
Download
Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.

Preview Molecular Allergy Diagnostics: Innovation for a Better Patient Management

Jörg Kleine-Tebbe Thilo Jakob Editors Molecular Allergy Diagnostics Innovation for a Better Patient Management Forewords by Robert G. Hamilton and Stefan Vieths 123 Molecular Allergy Diagnostics Jörg Kleine-Tebbe • Thilo Jakob Editors Molecular Allergy Diagnostics Innovation for a Better Patient Management Foreword 1 by Robert G. Hamilton Foreword 2 by Stefan Vieths Editors Jörg Kleine-Tebbe, MD Thilo Jakob, MD Professor of Dermatology and Allergology Professor of Dermatology and Allergology Allergy and Asthma Center Westend Chairman of the Department of Outpatient Clinic Hanf Dermatology and Allergology Ackermann and Kleine-Tebbe University Medical Center Gießen and Berlin Marburg, Campus Gießen Germany Justus Liebig University Gießen Gießen Germany ISBN 978-3-319-42498-9 ISBN 978-3-319-42499-6 (eBook) DOI 10.1007/978-3-319-42499-6 Library of Congress Control Number: 2016963214 © Springer International Publishing Switzerland 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The editors gratefully thank Thermo Fisher Scientific, Phadia AB, Uppsala, Sweden, for the educational grant provided supporting English translation and language revision. Based partially on the German language edition: Molekulare Allergiediagnostik by Jörg Kleine-Tebbe, Thilo Jakob. © Springer-Verlag Berlin Heidelberg 2015 Springer-Verlag is part of Springer Science+Business Media All Rights Reserved Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Foreword 1 Since 1967, when immunoglobulin E (IgE) was identified as the reagin in the blood that could transfer allergic sensitization, allergists have been striving to achieve increasingly “allergen-s pecific” diagnoses to help their patients with more targeted management strategies. In the USA in particular, complex allergen extracts have been almost exclu- sively used in both, in vivo (skin test and provocation testing) and in vitro (serological IgE antibody) assays. Of the 1269 extracts used in vivo for diagnosis in the USA, only 19 have limited “standardization.” Thus, the remaining 1250 extracts have no defined potency, no known composition, and no documented stability. Importantly, 45 % of extracts used in skin testing have no peer-reviewed literature documenting their efficacy and may be deleted from use in the USA. Moreover, extracts cannot readily differentiate between primary sensitization and immunological cross-r eactivity, and they cannot pre- dict risk or identify a prognostically significant sensitization. Despite these serious limi- tations, these crude extracts are being exclusively used in allergy diagnosis throughout North America because they are grandfathered by regulatory agencies, relatively easy to prepare, and are thought to contain the most comprehensive profile of allergens of clini- cal relevance achievable for that specificity. The increasing availability of clinically relevant allergenic molecules has begun to change the manner in which allergy diagnosis is performed. The age of “molecu- lar allergology” has brought with it the promise of enhanced specificity and increased predictability for serious allergic reactions. Much of the innovative sci- ence related to allergenic molecules has emerged from basic and clinical studies performed in Europe. Thus, it is fitting that this excellent, comprehensive, practical text entitled Molecular Allergy Diagnostics has been edited by our German col- leagues Drs. Kleine-Tebbe and Jakob. They have succeeded in obtaining authorita- tive and well-referenced reviews from the most experienced and knowledgeable authors from all over the world on topics relating to the allergenic plant and animal protein families and cross-reactive allergens due to their structure similarity. Despite the expanding repertoire of allergenic molecules available for serological dissection of the patient’s IgE antibody sensitization profile, the North American allergist has been slow to adopt most of the available molecular allergen-specific IgE analyses into their routine diagnostic algorithm. The exceptions are peanut (Ara h 1, 2, 3, 8, and 9) and hazelnut (Cor a 1, 8, 9, and 14) where distinction can be made between cross-reactive and primary sensitization and in some cases relative risk for serious allergic reactions. v vi Foreword 1 Drs. Kleine-Tebbe and Jakob and the contributing authors of Molecular Allergy Diagnostics are to be commended for their hard work and insightful preparation of this practical guide. This text serves as a unique, comprehensive, and simplified guidance with practical applications of the clinically important molecular allergen families as they are increasingly applied to the mainstream diagnostic algorithm for human allergic disease. For North American allergists who will probably not see recombinant molecular allergens used in skin testing or therapy, this textbook serves as a well-written primer on the topic of molecular allergen families available in IgE antibody serology and how they can enhance the accuracy (analytical and subse- quently diagnostic sensitivity and specificity) of allergic diagnosis. This textbook also serves as a comprehensive compendium of the current science related to the application of allergen molecules in the diagnosis of the allergic patient. It is a must read for clinicians, clinical and research laboratory personnel, and governmental regulators who are involved in the use, interpretation, or regulation of allergen reagents and IgE antibody measurement used in allergy diagnosis. Finally, the lay public who suffer from allergic disease will enjoy reading this well-organized text while also gaining a clearer understanding of how diagnostic molecular allergens can simplify the complexity of their disease. Robert G. Hamilton, Ph.D., D.ABMLI Professor of Medicine and Pathology Johns Hopkins University School of Medicine, and Director of the Johns Hopkins Dermatology, Allergy and Clinical Immunology Reference Laboratory, Baltimore, MD, USA Foreword 2 The term “molecular allergology” refers to the use of allergen molecules or particu- lar fragments, such as peptides or carbohydrate chains for the diagnosis and allergen- specific immunotherapy of allergic diseases. The focus of this book is a clear and practice-oriented introduction to this complex topic. The first allergens, from house dust mite and birch pollen, were cloned in the late 1980s, becoming available as highly purified recombinant proteins for molecular allergy research. The enormous potential for basic and clinical research was quickly recognized. Since then, more than 1000 allergen sequences have been identified. The availability of molecular allergens has caused a quantum leap in the field of allergy and offers great potential for the diagnosis and treatment of allergic diseases. The following areas of application are particularly worthy of note: • Molecular-level studies on the mechanisms of type-I allergies (IgE-mediated immediate-type hypersensitivity reactions) • Analysis of the B- and T-cell epitopes of allergens, with the goal of optimizing allergen-specific immunotherapy (AIT) • Study on the mode of action of AIT • Differentiation between clinically important and less relevant allergens from an allergen source or from comparable allergen families of different allergen sources • Development of innovative immunotherapeutics of precisely defined composi- tion and dosage • Potential for the development of personalized mixtures of recombinant allergens for immunotherapy Molecular diagnostics using single allergens is without doubt the area of applica- tion that has seen the greatest development and has already found its way into many areas of clinical routine. For allergists not primarily involved in research or molecu- lar diagnostics, the multitude of publications on the topic can be confusing: What are the clinical consequences, e.g., of IgE binding to strongly cross-reactive minor allergens vs. species-specific major allergens from pollen? Which treatment recom- mendations for AIT can be derived from this? Should IgE responses to cross-r eactive carbohydrate epitopes be classified as clinically irrelevant? Are all patients with IgE to the major allergen Ara h 2 from peanut at significant risk of anaphylaxis? Are vii viii Foreword 2 these patients at high risk of reacting to trace quantities of peanut? Is the evidence solid enough to form the basis for recommendations for routine clinical practice? This work addresses these questions by elaborating the background of molecular allergology in an easily comprehensible manner, hopefully without succumbing to the temptation to over-interpret the often exciting science uncovered in this still- evolving field. The authors, many of them well-known allergy researchers in German-speaking countries, have attempted to impart the interdisciplinary funda- mentals in a clear and concise manner. The boundaries of serological IgE diagnostics using single allergens are also clearly defined: Each IgE test represents a detection of sensitization, equivalent to an increased predisposition to allergies, not an actual allergy test. The use of aller- gen components changes nothing in this regard; the guidelines and basic principles of allergy diagnostics continue to remain valid. With this book, the editors have succeeded in making the field of molecular allergy diagnostics accessible to a wide readership, thereby smoothing the way to an increased application in clinical practice. Stefan Vieths, PhD Vice President of the Paul-Ehrlich-Institut, and Deputy Research Manager of the Allergology Unit, Federal Institute for Vaccines and Biomedicines, Langen, Germany Preface Molecular Allergology: From Research Topic to Innovative Allergy Diagnosis Allergology—the recognition and treatment of allergic diseases—is regarded as an interdisciplinary field. Indeed, physicians with various organ specialties (i.e., der- matology, ENT, pediatrics, pulmonology) take care of allergic patients in Germany. In other countries, physicians practice as full specialists of allergy and clinical immunology. Immediate-type allergic reactions can affect multiple organs and all age groups. A multidisciplinary conceptual and detailed approach is key to under- standing patterns of allergic responses and sequelae. The “scientific method,” medi- cal detective work, and clinical experience go hand in hand here. Successfully practiced allergology always considers the whole person, seeks individual solu- tions, and requires narrative-based medicine. Rapid advances in modern allergy research have set this medically diverse spe- cialty on a new course. With purified and synthetically produced (recombinant) allergens, basic and clinical research have gained important reagents with which new areas of allergology can be explored and old problems surprisingly easily solved. ix x Preface This work on molecular allergology summarizes the most important develop- ments of recent years. The first section presents examples of various allergic plant protein families and structurally related allergens, such as the Bet v 1 homologs/ PR-10-like proteins, profilins, polcalcins, lipid transfer proteins, and storage pro- teins. This is followed by an introduction to animal allergens from the lipocalin, albumin, and Ca++-binding protein families. Thus, the biological definition of important allergen sources (e.g., pollen, mites, mammals, molds, and foods) is expanded to a molecular dimension. It is, in fact, the actual allergic constituents that really matter! The second section deals with methods of immunoglobulin E (IgE) determina- tion to identify specific allergenic triggers: single determinations using singleplex or allergen screening using multiplex assays. Which type of diagnostician are you? Hunter or gatherer? Single allergens primarily improve the accuracy of IgE determi- nations, the test variants of which will be discussed in detail. The basic diagnostic rules remain unchanged: Positive IgE tests are only relevant in the case of corre- sponding symptoms. Thus, the individual patient history, quantifiable challenge tests, and astute interpretation retain their central importance in allergy diagnostics. Ultimately, it is the physician who determines the clinical relevance of allergy find- ings, not the test. The third section is devoted to molecular allergy diagnostics in routine clinical practice. How does one interpret symptoms conclusively and iden- tify reaction patterns correctly? How can one effectively enhance the accuracy of allergy diagnostics? Molecular allergology opens up new avenues—it begins when one “thinks molecular” and makes use of the testing options which have recently become available. The benefits and boundaries of molecular allergy diagnostics are discussed using the gamut of common allergen sources as a basis. The final section looks ahead to future applications of molecular allergology, such as the develop- ment of recombinant allergy vaccines and hypoallergenic foods. Molecular allergology is an exciting and rapidly developing field that has evolved from fragmented foci of research to an essential body of knowledge—particularly in relation to diagnostic questions in clinical allergology. It is our hope that, with this book, the authors will succeed in stimulating the reader’s enthusiasm for this still-evolving discipline and provide possibilities for its implementation in clinical routine. Well-targeted, specific allergy diagnostics will, hopefully, augment the counseling and treatment of allergic patients in the future. Berlin/Gießen, Germany Jörg Kleine-Tebbe January 2017 Thilo Jakob

See more

The list of books you might like

Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.