Swiss Institute of Allergy and Asthma Research SIAF

Davos, Switzerland

Swiss Institute of Allergy and Asthma Research SIAF

Davos, Switzerland

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Akdis C.A.,University of Zürich | Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis M.,University of Zürich
Journal of Allergy and Clinical Immunology | Year: 2011

Allergen-specific immunotherapy has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific method of treatment. The mechanisms of action of allergen-specific immunotherapy include the very early desensitization effects, modulation of T-and B-cell responses and related antibody isotypes, and migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T (Treg) cells have been identified as key regulators of immunologic processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in patients undergoing allergen-specific immunotherapy. Naturally occurring forkhead box protein 3-positive CD4 +CD25 + Treg cells and inducible T R1 cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector T H1, T H2, and T H17 cells; suppression of allergen-specific IgE and induction of IgG4; suppression of mast cells, basophils, and eosinophils; and suppression of effector T-cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and Treg cell subsets. © 2010 American Academy of Allergy, Asthma & Immunology.


Crameri R.,University of Zürich | Crameri R.,Swiss Institute of Allergy and Asthma Research SIAF
Seminars in Immunopathology | Year: 2015

Despite the increasing number of solved crystal structures of allergens, the key question why some proteins are allergenic and the vast majority is not remains unanswered. The situation is not different for fungal allergens which cover a wide variety of proteins with different chemical properties and biological functions. They cover enzymes, cell wall, secreted, and intracellular proteins which, except cross-reactive allergens, does not show any evidence for structural similarities at least at the three-dimensional level. However, from a diagnostic point of view, pure allergens biotechnologically produced by recombinant technology can provide us, in contrast to fungal extracts which are hardly producible as standardized reagents, with highly pure perfectly standardized diagnostic reagents. © 2014, Springer-Verlag Berlin Heidelberg.


Soyka M.B.,University of Zürich | Soyka M.B.,Swiss Institute of Allergy and Asthma Research SIAF | Nikolaou G.,University of Zürich | Rufibach K.,University of Zürich | Holzmann D.,University of Zürich
Rhinology | Year: 2011

Background: Epistaxis represents one of the most common emergencies in ENT clinics around the world. It creates great physical and emotional stress to the patient as well as a financial burden on health-care systems. A lot of research has been performed with regard to aetiology and possible treatment, however, not much effort has been put into analysing the effectiveness of common treatment forms. It is the objective of this study to clarify which of these treatment forms is reliable. Study design: Retrospective cohort study. Level of Evidence: 2b. Methods: Between 03/2007 and 04/2008, all epistaxis therapies including relapses and treatment failures at the University Hospital of Zurich have been documented using a computerised questionnaire. Different treatments were compared to each other. Results: An analysis of 678 interventions in 537 patients was performed with emphasis on failure proportions and time to occurrence. The estimated failure proportions of coagulation in anterior epistaxis accounts for 14%. Successful treatment of epistaxis in posterior bleedings could be achieved in 62% by packing and in 97% by surgery with a statistically significant difference between the respective groups. Conclusion: Using our treatment options, anterior epistaxis can be cured reliably by cauterisation. Surgical therapies in posterior bleedings are able to successfully salvage failed packing therapies.


Novak N.,University of Bonn | Mete N.,Swiss Institute of Allergy and Asthma Research SIAF | Mete N.,Ege University | Bussmann C.,University of Bonn | And 6 more authors.
Journal of Allergy and Clinical Immunology | Year: 2012

Background: Early desensitization of FcεRI-bearing mast cells and basophils has been demonstrated in allergen-specific immunotherapy and drug desensitization. However, its mechanisms have not been elucidated in detail. Histamine is one of the main mediators released on FcεRI triggering of basophils and mast cells, and it exerts its functions through histamine receptors (HRs). Objectives: We sought to investigate HR expression on basophils of patients undergoing venom immunotherapy (VIT) and its effect on allergen, IgE, and FcεRI cross-linking-mediated basophil function and mediator release. Methods: Basophils were purified from the peripheral blood of patients undergoing VIT and control subjects and were studied functionally by using real-time PCR, flow cytometry and ELISA assays. Results: Rapid upregulation of H2R within the first 6 hours of the build-up phase of VIT was observed. H2R strongly suppressed FcεRI-induced activation and mediator release of basophils, including histamine and sulfidoleukotrienes, as well as cytokine production in vitro. Conclusion: Immunosilencing of FcεRI-activated basophils by means of selective suppression mediated by H2R might be highly relevant for the very early induction of allergen tolerance and the so-called desensitization effect of VIT. © 2012 American Academy of Allergy, Asthma & Immunology.


Bekpen C.,Swiss Institute of Allergy and Asthma Research SIAF | Bekpen C.,Bogazici University | Tastekin I.,Bogazici University | Siswara P.,University of Washington | And 3 more authors.
Genome Research | Year: 2012

The LRRC37 gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes, BPTF and DND1, respectively. Two of these more broadly expressed gene family members, LRRC37A1 and A4, define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (the MAPT locus) - a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of the LRRC37 family occurred in a stepwise manner, acquiring foreign promoters from BPTF and DND1 via segmental duplication. This unusual evolutionary trajectory altered the regulation of the LRRC37 family, leading to increased expression in the fetal brain and cerebellum.


Ozdemir C.,Swiss Institute of Allergy and Asthma Research SIAF | Ozdemir C.,Marmara University | Kucuksezer U.C.,Istanbul University | Akdis M.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF
Clinical and Experimental Allergy | Year: 2011

Hymenoptera venoms are important allergens that can elicit both local and systemic allergic reactions, including life-threatening anaphylaxis. Venom immunotherapy (VIT) remains the most effective treatment, reducing the risk of systemic reactions in individuals with Hymenoptera venom allergy. VIT can restore normal immunity against venom allergens and provide patients with a lifetime of tolerance to venoms. During VIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T (Treg) cells, which suppress proliferative and cytokine responses against the venom allergens. Treg cells are characterized by IL-10 secretion that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Treg cells also have influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies against venom allergens. An accumulating body of evidence suggests that Treg cells may affect allergen sensitization and methods for enhancing this cell population may eventually improve the efficacy of VIT. In this article, immune mechanisms enrolled in bee and wasp VIT are reviewed. © 2011 Blackwell Publishing Ltd.


Ozdemir C.,Marmara University | Akdis M.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF
Chemical Immunology and Allergy | Year: 2010

Anaphylaxis is a life-threatening IgE-dependent type 1 hypersensitivity reaction in which multiple organ systems are involved. The existence of allergen exposure and specific IgE are the major contributors to this systemic reaction. The decision of the immune system to respond to allergens is highly dependent on factors including the type and load of allergen, behavior and type of antigen-presenting cells, innate immune response stimulating substances in the same micromilieu, the tissue of exposure, interactions between T and B lymphocytes, costimulators, and genetic propensity known as atopy. Antigen-presenting cells introduce processed allergens to T-helper lymphocytes, where a decision of developing different types of T-cell immunity is given under the influence of several cytokines, chemokines, costimulatory signals and regulatory T cells. Among Th2-type cytokines, interleukin (IL)-4 and IL-13 are responsible for class switching in B cells, which results in production of allergen-specific IgE antibodies that bind to specific receptors on mast cells and basophils. After re-exposure to the sensitized allergen, this phase is followed by activation of IgE Fc receptors on mast cells and basophils resulting in biogenic mediator releases responsible for the symptoms and signs of anaphylaxis. Since the discovery of regulatory T cells, the concepts of immune regulation have substantially changed during the last decade. Peripheral T-cell tolerance is a key immunologic mechanism in healthy immune response to self antigens and non-infectious non-self antigens. Both naturally occurring CD4+CD25+ regulatory T (Treg) cells and inducible populations of allergen-specific, IL-10-secreting Treg type 1 cells inhibit allergen-specific effector cells and have been shown to play a central role in the maintenance of peripheral homeostasis and the establishment of controlled immune responses. On the other hand, Th17 cells are characterized by their IL-17 (or IL-17A), IL-17F, IL-6, tumor necrosis factor-α, and IL-22 expressions, which coordinate local tissue inflammation through upregulation of proinflammatory cytokines and chemokines. This chapter is mainly focused on antigen presentation pathways and allergen-specific T-cell responses. Copyright © 2010 S. Karger AG, Basel.


Akkoc T.,Marmara University | Akdis M.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF
Allergy, Asthma and Immunology Research | Year: 2010

Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research. © The Korean Academy of Asthma, Allergy and Clinical Immunology. The Korean Academy of Pediatric Allergy and Respiratory Disease.


Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis C.A.,Christine Kuhne Center for Allergy Research and Education | Akdis M.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis M.,Christine Kuhne Center for Allergy Research and Education
Science Translational Medicine | Year: 2015

Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a tolerance-inducing therapy for allergic diseases and represents a potentially curative method of treatment. AIT functions through multiple mechanisms, including regulating T and B cell responses, changing antibody isotypes, and decreasing mediator release and migration of eosinophils, basophils, and mast cells to affected tissues. Despite the relative success of AIT, attempts are being made to improve this therapy in order to overcome problems in standardization, efficacy, safety, long duration of treatment, and costs. These have led to the development of biotechnological products with successful clinical results. © 2015, American Association for the Advancement of Science. All rights reserved.


Akdis C.A.,Swiss Institute of Allergy and Asthma Research SIAF | Akdis M.,Swiss Institute of Allergy and Asthma Research SIAF
World Allergy Organization Journal | Year: 2015

Abstract Substantial progress in understanding mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumors, organ transplantation and chronic infections has led to a variety of targeted therapeutic approaches. Allergen-specific immunotherapy (AIT) has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific way of treatment. The mechanisms by which allergen-AIT has its mechanisms of action include the very early desensitization effects, modulation of T- and B-cell responses and related antibody isotypes as well as inhibition of migration of eosinophils, basophils and mast cells to tissues and release of their mediators. Regulatory T cells (Treg) have been identified as key regulators of immunological processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in AIT. Naturally occurring FoxP3+ CD4+CD25+ Treg cells and inducible type 1 Treg (Tr1) cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector Th1, Th2 and Th17 cells; suppression of allergen-specific IgE, and induction of IgG4; suppression of mast cells, basophils and eosinophils and suppression of effector T cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and regulatory T cell subsets. © 2015 Akdis and Akdis; licensee BioMed Central.

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