A number of advances in the scientific knowledge concerning adverse food reactions have been made in the past few years. Understanding about the nature of the food allergen itself, the molecular characterization of the epitopes on these allergens, the pathophysiology of the clinical reaction, and the diagnostic methods have all been significantly enhanced.
Sublingual immunotherapy (SLIT) is an efficacious and safe alternative to subcutaneous immunotherapy (SCIT). During the last three decades, SLIT has been widely used in many countries, primarily in central and southern Europe, where more than 50% of the current population of patients receiving specific immunotherapy are on SLIT (1).
Many fungi are capable of causing IgE-mediated hypersensitivity in humans. However, the most predominant fungi implicated in allergy belong to the genera Aspergillus, Alternaria, Cladosporium , and Penicillium . Pure and relevant allergens are essential for diagnosis as well as for understanding the immunopathogenesis of the disease. Until recently, pure and standardizable antigens from fungi were not available. In recent years, many recombinant allergens have been produced by molecular cloning. Using these allergens, novel methods are being developed to improve diagnosis of mold-induced allergy. By understanding the immunopathogenesis of allergens, new avenues might open up leading to improved patient care, including immunotherapy and vaccination. This review covers the current status of fungal allergens, their role in reliable immunodiagnosis, and their probable use in immunotherapy and vaccination.
Atopy--the genetic predisposition to produce allergen-specific IgE is one of the most important predisposing factors for the development of asthma and other allergic diseases. Because of pivotal place of IgE in early and late phase e of allergic responses the introduction of anti-IgE antibodies to therapy provides a novel and promising approach to treatment of asthma and other IgE-dependent diseases. The administration of anti-IgE reduces circulating IgE levels to less than 1% of the baseline value and down-regulates the expression of basophil IgE receptors. Anti-IgE antibody rhuMAb E25 (omalizumab) improved asthma symptoms, reduced the rates of exacerbations and allowed for the reduction of corticosteroids and rescue medication doses. Anti-IgE therapy is safe and well tolerated.
There is an increasing awareness of the health implications of mite sensitivity, as it is closely related to asthma. Mite allergy constitutes a complex worldwide problem, with sanitary and economical implications. Not only are mite species present in house dust, producing potent allergens, but other, less studied species are also responsible for significant allergic reactions in occupational settings. In this review, we focus on the growing number of mite species that are implicated in allergic cutaneous and respiratory diseases in humans. Mite allergy is not restricted only to the human “indoor” environment, because numerous reports clearly demonstrate that many species that can induce sensitization and symptoms are encountered in occupational settings. An important component of allergy research is the evaluation of the allergenic cross-reactivity to verify to what extent different mite species have unique, species-specific, or cross-reactive allergens. The results of these investigations have important clinical consequences for the diagnosis and treatment of allergic diseases. Internationally standardized mite extracts are needed to compare sensitization rates around the world and clearly establish risk factors associated with sensitization and asthma. In spite of recent controversial results, a significant reduction in the exposure to mite allergens continues to be an important challenge and one of the main goals in the treatment of mite-induced respiratory symptoms. In many cases, this reduction must be achieved in the workplace as well as in the home environment.
This chapter reviews the immunochemical properties of some of these known Hymenoptera venom proteins and peptides, and their relevance to understanding and treatment of insect allergy. Several authors have reported the use of venom allergens for improved diagnosis of Hymenoptera hypersensitivity. In addition to proteins, Hymenoptera venoms contain peptides, biogenic amines such as histamine and dopamine, and other low-molecular-weight components. The host protein is homologous to the guest allergen and they are poorly cross-reactive as antigens. Data in agreement with the generalization were obtained with vespid allergen-specific mouse antisera, which contain mainly specific immunoglobulin G. Mediators are released from immunoglobulin E (IgE)-bound mast cells or basophils on allergen challenge. This biological activity requires the allergens to have multiple determinants/epitopes so that they can cross-link the bivalent IgE antibodies. The biological activity of allergens to cause mediator release depends on the affinity of allergen-specific IgEs.
Allergens are embedded into the protein universe as members of large families and superfamilies of related proteins which is a direct consequence of their shared evolution. The classification of allergens by protein families offers a valuable frame of reference that allows the design of experiments to study cross-reactivity and allergenic potency of proteins. Information on protein family membership also complements the current official IUIS allergen nomenclature. All presently known allergens belong to one of 140 (1.4%) of the 10,340 protein families currently described by version 23.0 of the Pfam database. This is indicative of a strong bias among allergens towards certain protein architectures that are able to induce an IgE response in an atopic immune system. However, even small variations in the structure of a protein alter its immunological characteristics. Various isoforms of the major birch pollen allergen Bet v 1 were shown to possess highly variant immunogenic and allergenic properties. Ber e 1 and SFA8, two 2S albumins, were revealed to display differential capacities to polarise an immune response. Such data will be exploited in the future for the design of allergy vaccines.
Allergen vaccines are complex biologic mixtures in which standardization is essential to ensure efficacy and safety in allergic diagnosis and therapy. Statistically, a patient's IgE will bind to some allergens more frequently than others, thereby defining major allergens. All allergens are proteins and all soluble proteins are potential allergens. For major allergens, micrograms are the useable measure for optimal clinical maintenance doses. Recombinant allergens are likely to replace natural allergens in the future.
This chapter reviews the taxonomy, ecology, and habitat of allergenic grasses belonging to the family Poaceae and the molecular characteristics of the 13 grass pollen allergen groups recognized by the International Union of Immunological Societies Allergen Nomenclature Sub-Committee. The chapter describes how various techniques of molecular biology and protein chemistry are used to define allergenically important and cross-reactive IgE-binding epitopes, to develop specific assays for allergen detection and quantitation, to delineate determinants involved in B- and T-cell recognition, and to design novel approaches for allergen immunotherapy. The clinical relevance of the observed cross-reactivities among grass pollen allergens and those between homologous proteins derived from other pollen sources, fruits, and vegetables is discussed.
R. Koch's and Louis Pasteur's early endeavors to develop preventive vaccines were innovative giant steps in establishing immunization as an efficacious measure in disease prevention. With the growing appreciation of pollens as allergens, the concept of pollen "toxin" faded and the objective of immunotherapy took on a new meaning. The ability of posttreatment serum to inhibit reactions between serum-containing reaginic antibody and corresponding pollen allergen at passively sensitized cutaneous test sites by the technique of Prausnitz and Kustner was attributed to the effects of "blocking antibody" induced by injection treatment. Several groups have demonstrated that intralymphatic injection of allergen transdermal delivery of allergens may offer novel routes to achieve clinical improvement in atopic patients more rapidly than traditional schedules via either subcutaneous or sublingual routes. This historical perspective offers an opportunity to reflect upon the personalities of forbears in the specialty as they sought to apply and understand allergen immunotherapy used to treat their patients who suffer from atopic diseases.
Basics Allergen Immunotherapy in a Historical Perspective David Fitzhugh, Sheldon G. Cohen, and Richard Evans III (deceased) Definition of an Allergen (Immunobiology) Malcolm N. Blumenthal and Lauren Fine Allergen Nomenclature Heimo Breiteneder and Martin D. Chapman Immunological Responses to Subcutaneous Allergen Immunotherapy Mohamed H. Shamji, Stephen J. Till, and Stephen R. Durham Immunologic Responses to Sublingual Allergen Immunotherapy Ozge Soyer and Mubeccel Akdis Immunologic Responses to Oral Allergen Immunotherapy Sakura Sato and Motohiro Ebisawa In Vivo Testing for Allergic Diseases Richard W. Weber Serological (In Vitro) Testing Methods in the Diagnosis of Human Allergic Disease Robert G. Hamilton Allergens: Inhalation, Ingested, and Injected Tree Pollen Allergens Katharina Marth, Tetiana Garmatiuk, Ines Swoboda, and Rudolf Valenta Grass Pollen Allergens Robert E. Esch Weed Pollen Allergens Fatima Ferreira, Gabriele Gadermaier, Michael Hauser, and Michael Wallner Fungal Allergens Hari M. Vijay, Viswanath P. Kurup, and Jonathan A. Bernstein Mite Allergens Enrique Fernandez-Caldas, Leonardo Puerta, Luis Caraballo, and Richard F. Lockey Cockroach and Other Inhalant Insect Allergens Anna Pomes Mammalian Allergens Tuomas Virtanen, Tuure Kinnunen, and Marja Rytkonen-Nissinen Food Allergens Mike Kulis and A. Wesley Burks Hymenoptera Allergens Te Piao King and Miles Guralnick Biting Insect and Tick Allergens Donald R. Hoffman Occupational Allergens Andrew M. Smith and David I. Bernstein Immunotherapy Techniques: Preparation and Administration of Subcutaneous and Sublingual Allergen Immunotherapy Standardized Allergen Vaccines in the United States Ronald L. Rabin and Jay E. Slater Manufacturing and Standardizing Allergen Extracts in Europe Jorgen Nedergaard Larsen, Christian Gauguin Houghton, Manuel Lombardero Vega, and Henning Lowenstein Preparing Subcutaneous Allergen Vaccines Harold S. Nelson Preparing and Administering Sublingual Allergen Vaccines Miguel Casanovas and Enrique Fernandez-Caldas Subcutaneous Administration of Allergen Vaccines Sarah Peterson and Leslie C. Grammer Administration of Sublingual Vaccines Giovanni Passalacqua and Giorgio Walter Canonica Subcutaneous Immunotherapy for Allergic Rhinoconjunctivitis, Allergic Asthma, and Prevention of Allergic Diseases Hans-Jorgen Malling and Jean Bousquet Sublingual Immunotherapy for Allergic Rhinoconjunctivitis, Allergic Asthma, Food Allergy, and Prevention of Allergic Diseases Moises A. Calderon, Martin Penagos, and Stephen R. Durham Oral Immunotherapy for Food and Latex Allergy Anna Nowak-Wegrzyn and Scott H. Sicherer Immunotherapy for Hymenoptera Venom Hypersensitivity Ulrich Muller, David B. K. Golden, Richard F. Lockey, and Byol Shin Other Types of Immunotherapy Recombinant and Modified Vaccines and Adjuvants Used for Allergen Immunotherapy Nana Fenny, Vesselin V. Dimov, and Thomas B. Casale Anti-IgE Therapy Eckard Hamelmann and Ulrich Wahn Unproven and Controversial Forms of lmmunotherapy Haig Tcheurekdjian and Abba I. Terr Prevention and Management of Adverse Effects Adverse Effects and Fatalities Associated with Allergen Skin Testing and Subcutaneous Allergen Immunotherapy Andrew S. Bagg and Richard F. Lockey Adverse Effects Associated with Sublingual Immunotherapy Giovanni Passalacqua and Erkka Valovirta Adverse Effects Associated with Oral Allergen Immunotherapy Robert A. Wood Recognition, Treatment, and Prevention of Anaphylaxis Stephen F. Kemp and Richard D. deShazo Instruction and Consent Forms for Subcutaneous Allergen Immunotherapy Linda Cox and Richard F. Lockey Information and Consent Forms for Sublingual and Oral Allergen Immunotherapy Pascal Demoly and Claude Andre (deceased) Index
