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Genetic Environmental Factors in Clinical Allergy

Genetic Environmental Factors in Clinical Allergy

David G. Marsh
Malcolm N. Blumenthal
Copyright Date: 1990
Edition: NED - New edition
Pages: 208
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  • Book Info
    Genetic Environmental Factors in Clinical Allergy
    Book Description:

    Genetic Environmental Factors in Clinical Allergy was first published in 1990. In 1979, the Task Force on Asthma and the Other Allergic Diseases, organized by the U.S. Department of Health and Human Services, estimated (conservatively) that 35 million residents of the United States suffered from asthma and other serious allergies, spending “well in excess of $1 billion each year for physicians’ services, drugs, and hospital and nursing care.” Asthma deaths in the U.S. were estimated to be between 2,000 and 4,000 annually; further deaths were shown to result from severe allergic reaction to insect stings, foods, and certain drugs. An understanding of the genetic and environmental factors that determine atopic allergy, which includes diseases such as hay fever, asthma, atopic dermatitis (eczema), and certain types of food intolerance, is vital to the diagnosis, prevention, and treatment of this multifaceted disease. In this volume, David G. Marsh and Malcolm N. Blumenthal have assembled the work of leading experts to address a broad range of theoretical, experimental, and clinical aspects of atopic allergy. Areas covered include a historical introduction to the subject, the selection criteria and methodology used to evaluate the subjects’ specific immunologic responses, a tabulation of the physiochemical properties of most of the well-characterized purified allergens, an addendum covering the most extensive national survey of the allergic sensitivity ever performed in the United States, and a review of environmental and developmental determinants of atopic disease that focuses on early childhood. Of special interest are the final five chapters that assess current research on the human immune system and human susceptibility to immunologic diseases -- atopic allergy is now regarded as the most appropriate model for approaching such problems.

    eISBN: 978-0-8166-5541-0
    Subjects: Health Sciences

Table of Contents

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  1. Front Matter
    (pp. i-iv)
  2. Table of Contents
    (pp. v-vi)
  3. Preface
    (pp. vii-2)
    D.G.M and M.N.B
  4. 1 Historical Introduction
    (pp. 3-9)
    David G. Marsh

    Heredity has long been suspected to play an important role in the development of asthma, hay fever, and other conditions generally referred to as “atopic allergic diseases,” which are now known to be mediated by IgE (1). Since much of the research carried out prior to 1960 has been extensively reviewed elsewhere (2-6), only the major findings will be discussed here. The early findings will be reviewed in the context of today’s knowledge about the genetics of the disease and as a prelude to discussions of recent data on the genetics and epidemiology of allergic disease in subsequent chapters.


  5. 2 Population Selection and Methods of Evaluating Immunologic Responses to Allergens
    (pp. 10-19)
    Malcolm N. Blumenthal

    Atopic allergy provides an excellent model for evaluating the genetics of the human immune system in relationship to disease processes. Atopic allergic diseases are common conditions in which we can identify both the antigen and the immune systems involved. Much useful information on the immunogenetics of IgE mediated diseases has been obtained using population, twin, and family studies (1,2).

    Many factors should be considered in the study of the immunogenetics of atopic disease. These include definition of parameters to be measured, study design, selection of subjects, and method of statistical analysis.

    The definitions of various atopic diseases vary with the...

  6. 3 Allergens and Allergen Nomenclature
    (pp. 20-31)
    David G. Marsh

    During the past 80 years, and especially since the early 1960s, there has been considerable effort on the part of many research groups to identify and characterize the specific components which commonly act as allergens in humans. In order to provide a better focus for these efforts, the IUIS Subcommittee for Allergen Nomenclature has introduced a systematic nomenclature (1). Both highly purified allergens and components identified within complex allergen source materials by techniques such as crossed immunoelectrophoresis (CIE) and isoelectricfocusing (IEF) (Chapter 4) are included within this system. The aim is to provide a unified nomenclature which will promote future...

  7. 4 The Relevance of Allergen Standardization and Purity to Epidemiologic and Genetic Studies of Immune Responses to Allergens
    (pp. 32-52)
    Marianne Roebber

    Epidemiologic or genetic studies which evaluate human immune responses to allergens are critically dependent on three variables; the group of people to be investigated, the techniques to be used to assess the immune responses, and the quality of the test allergens. The first two of these variables are discussed in Chapter 2. This chapter will deal with the third variable, the test allergens. Both complex allergenic extracts and single, highly purified components are usually needed for genetic studies. The complex extracts are needed to evaluate each person's overall allergic responsiveness, and the highly purified components are required for studies of...

  8. 5 Epidemiology of Atopic Allergy
    (pp. 53-72)
    Linda R. Freidhoff

    Many studies of atopic allergy have provided evidence for both an environmental and a genetic basis for the human immune response toward inhaled allergens (1-6). Gathered through retrospective cohort or population studies, epidemiologic data from many different groups of people differentially exposed to offending allergens are, however, difficult to compare due to varying definitions of allergic disease used by these workers and the numerous methods of collection and analyses employed (7-10). Furthermore, one of the major limitations of a retrospective cohort or population study is that it begins after the occurrences of both the causes and many of the effects...

  9. 5 Supplement Prevalence of Percutaneous Immediate Hypersensitivity and Histamine Reactivity in the U.S. Population: Data from the Second National Health and Nutrition Examination Survey
    (pp. 73-83)
    Peter J. Gergen and Paul C. Turkeltaub

    Allergen skin testing was performed during the second National Health and Nutrition Examination Survey (NHANES II) 1976-80, conducted by the National Center for Health Statistics (NCHS) (1). As a result, NHANES II, a national sample of the civilian noninstitutional population of the United States, offered the first opportunity to study skin-test reactivity in the general U.S. population. All 16,204 participants, six through 74 years of age, in the examination phase of NHANES II, were eligible to receive allergen skin testing; there were 14,164 whites and 2,040 blacks. Eight allergen and histamine skin tests were completed by 89.0% (12,606) of the...

  10. 6 Environmental and Developmental Factors in Allergic Disease in Infancy and Early Childhood
    (pp. 84-96)
    Bengt Björkstén and John W. Gerrard

    Development of allergic diseases is affected both by genetic and environmental factors. Environmental factors play an important role by modifying the phenotypic expression of the genotype. Recent studies indicate that the effects of the environment may be different on infants with and without genetic predisposition for allergy. Therefore, these environmental effects should be considered separately for babies possessing and babies not possessing certain defined markers often associated with subsequent development of allergy. Table 1 summarizes some environmental influences claimed to increase the risk of developing allergic disease.

    Many of the studies of environmental factors have been retrospective. While this approach...

  11. 7 Immunogenetic and Immunochemical Factors Determining Immune Responsiveness to Allergens: Studies in Unrelated Subjects
    (pp. 97-123)
    David G. Marsh

    Many highly purified allergens from different allergenic extracts have been isolated and characterized (Chapter 3), thereby facilitating genetic and molecular studies of specific immune responses to a wide variety of macromolecules. Beside improving our understanding of the genetic basis of allergy, these studies provide an excellent general model to investigate the genetic factors which control human immune responsiveness (1,2; Chapter 1). An important goal is to define the relationships between individuals’ immune response “fingerprints” to an array of well-defined antigens (Ags) and the presence of polymorphic genetic markers that play key roles in controlling specific immune responses. Such knowledge will...

  12. 8 Genetic Control of IgE Antibody Responses in Humans The Amb V (Ra5) Model
    (pp. 124-131)
    Kelsye M. Coulter, Guérin Dorval and Lawrence Goodfriend

    The existence of a genetic control of specific immune responses in mammals surfaced in the early 1960’s with the discovery by Benacerraf and colleagues (1) of low and high antibody responder strains to the hapten-carrier conjugate dinitrophenyl-poly-L-lysine (DNP-PLL) in guinea pigs. The defect in a low responder strain was not due to the inability to mount an anti-hapten (anti-DNP) response since immunization of the low responders with DNP-PLL coupled to the more complex carrier, ovalbumin, resulted in a high anti-DNP antibody response. Studies initiated by these seminal observations (2) led to the current concept that immune response(Ir)genes located...

  13. 9 Immunogenetics of Specific Immune Responses to Allergens in Twins and Families
    (pp. 132-142)
    Malcolm N. Blumenthal and Sergio Bonini

    The immune response system is complex and involves a variety of mechanisms, some of which have a genetic basis. A great deal of the recent knowledge in the field of immunogenetics has arisen from studies of the major histocompatibility complex (MHC) (Chapter 7). Initially, the significance of the MHC was confined to the field of transplantation, as it is a genetic region that has a major influence on graft rejection (1, 2). The first model involved in studying the histocompatibility antigens was in the mouse (3). Many species of mammals (including humans) and birds have been found to have homologous...

  14. 10 Genetic Aspects of Bronchial Hyperreactivity
    (pp. 143-152)
    Russell J. Hopp, Nicki M. Nair, Againdra K. Bewtra and Robert G. Townley

    The hallmark of bronchial asthma is hypersensitivity of the airways to specific and nonspecific chemicals, physical stimuli, and pharmacologic agents. Asthmatic subjects develop bronchospasm during bronchoprovocative challenge with the parasympathetic agents methacholine, carbacholine, acetylcholine, and pilocarpine. Histamine and serotonin can cause bronchospasm as can the arachidonic acid metabolites prostaglandin F₂-alpha and leukotrienes C₄, D₄, and possibly E₄. In addition, the natural challenges of exercise, cold air, hyperventilation, and the inhalation of hypotonic water and hypertonic saline can also induce bronchospasm.

    Although asthmatics are 100 to 1,000 times more sensitive to these challenges, other individuals occasionally demonstrate bronchial hyperreactivity. Subjects with...

  15. 11 The Role of Genetic and Environmental Factors in the Control of Basophil and Mast Cell Releasability
    (pp. 153-160)
    Gianni Marone, Vincenzo Casolaro, Domenico Celestino and Sergio Bonini

    There is now compelling evidence that several immune and inflammatory functions in atopic individuals differ from those in non-atopic subjects. These abnormal functions can be divided into three main categories: a) increased IgE antibody responses, b) increased releasability of chemical mediators from basophils and mast cells, and c) increased responsiveness of end-organs such as bronchial smooth muscle to mediators.

    IgE antibody response to antigen is the classical means of distinguishing allergic and non-allergic individuals (1). As a group, allergic individuals have significantly higher serum IgE levels and greater numbers of IgE receptors on their basophils than do normal subjects (2)....

  16. 12 Family Analysis and Genetic Counseling for Allergic Diseases
    (pp. 161-176)
    Deborah A. Meyers

    The aims of this chapter are twofold: 1) to review the major statistical methods used in genetic analysis of family data, with examples taken from studies of total serum IgE levels, and 2) to show how the results from such analyses can be used to predict recurrence risks in a given family as an eventual approach to “family counseling.” A review of the literature on the genetics of allergy will not be given here; the reader is referred to Chapters 1,7, and 9. However, since there have been several family studies of total serum IgE levels using state-of-the-art genetic methods,...

  17. Glossary
    (pp. 177-180)
  18. Contributors
    (pp. 181-184)
  19. Index
    (pp. 185-196)
  20. Back Matter
    (pp. 197-197)