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      EAACI Allergen Immunotherapy User's Guide

      research-article
      1 , 2 , 3 , 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 17 , 21 , 22 , 23 , 18 , 19 , 22 , 17 , 24 , 25 , 26 , 27 , 28 , 15 , 15 , 4 , 29 , 30 , 12 , 13 , 18 , 19 , 31 , 32 , 33
      Pediatric Allergy and Immunology
      John Wiley and Sons Inc.
      Allergy, immune regulation, immunotherapy, tolerance

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          Abstract

          Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on a well‐defined immunologic mechanism promoting regulatory T cells and downplaying the immune response induced by allergens. Clinical indications have been well documented for respiratory allergy in the presence of rhinitis and/or allergic asthma, to pollens and dust mites. Patients who have had an anaphylactic reaction to hymenoptera venom are also good candidates for allergen immunotherapy. Administration of allergen is currently mostly either by subcutaneous injections or by sublingual administration. Both methods have been extensively studied and have pros and cons. Specifically in children, the choice of the method of administration according to the patient's profile is important. Although allergen immunotherapy is widely used, there is a need for improvement. More particularly, biomarkers for prediction of the success of the treatments are needed. The strength and efficiency of the immune response may also be boosted by the use of better adjuvants. Finally, novel formulations might be more efficient and might improve the patient's adherence to the treatment. This user's guide reviews current knowledge and aims to provide clinical guidance to healthcare professionals taking care of children undergoing allergen immunotherapy.

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          Most cited references639

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          Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2016 revision.

          Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update.
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            Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

            There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.
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              Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells

              Alum (aluminum hydroxide) is the most widely used adjuvant in human vaccines, but the mechanism of its adjuvanticity remains unknown. In vitro studies showed no stimulatory effects on dendritic cells (DCs). In the absence of adjuvant, Ag was taken up by lymph node (LN)–resident DCs that acquired soluble Ag via afferent lymphatics, whereas after injection of alum, Ag was taken up, processed, and presented by inflammatory monocytes that migrated from the peritoneum, thus becoming inflammatory DCs that induced a persistent Th2 response. The enhancing effects of alum on both cellular and humoral immunity were completely abolished when CD11c+ monocytes and DCs were conditionally depleted during immunization. Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid. These findings suggest that alum adjuvant is immunogenic by exploiting “nature's adjuvant,” the inflammatory DC through induction of the endogenous danger signal uric acid.
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                Author and article information

                Journal
                Pediatr Allergy Immunol
                Pediatr Allergy Immunol
                10.1111/(ISSN)1399-3038
                PAI
                Pediatric Allergy and Immunology
                John Wiley and Sons Inc. (Hoboken )
                0905-6157
                1399-3038
                21 May 2020
                May 2020
                : 31
                : Suppl 25 , EAACI Allergen Immunotherapy in Children User's Guide. Editor in Chief: Philippe Eigenmann. Guest Editor: Montserrat Alvaro‐Lozano and Marta Vazquez‐Ortiz ( doiID: 10.1111/pai.v31.s25 )
                : 1-101
                Affiliations
                [ 1 ] Pediatric Allergy and Clinical Immunology Service Hospital Sant Joan de Déu Barcelona Spain
                [ 2 ] Swiss Institute of Allergy and Asthma Research (SIAF) University of Zurich Davos Switzerland
                [ 3 ] Christine Kühne‐Center for Allergy Research and Education Davos Switzerland
                [ 4 ] The David Hide Asthma and Allergy Research Centre St Mary's Hospital Newport Isle of Wight UK
                [ 5 ] Clinical and Experimental Sciences and Human Development and Health Faculty of Medicine University of Southampton Southampton UK
                [ 6 ] NIHR Southampton Biomedical Research Centre University Hospital Southampton NHS Foundation Trust Southampton UK
                [ 7 ] Primary Care and Population Sciences University of Southampton Southampton UK
                [ 8 ] Pediatric Allergology Unit Department of Pediatric Medicine Bambino Gesù Children's research Hospital (IRCCS) Rome Italy
                [ 9 ] Department of Clinical Immunology and Allergology I.M. Sechenov First Moscow State Medical University Moscow Russia
                [ 10 ] School of Medicine Institute for Applied Molecular Medicine (IMMA) Universidad CEU San Pablo Madrid Spain
                [ 11 ] RETIC ARADYAL RD16/0006/0015 Instituto de Salud Carlos III Madrid Spain
                [ 12 ] Allergy Department Hospital Infantil Niño Jesús Madrid Spain
                [ 13 ] ARADyAL RD16/0006/0026
                [ 14 ] Department of Paediatric Allergy and Immunology Faculty of Medicine Goztepe Training and Research Hospital Istanbul Medeniyet University Istanbul Turkey
                [ 15 ] Pediatric Allergy and Clinical Immunology Service Institut de Reserca Sant Joan de Déu Barcelona Spain
                [ 16 ] Department of Clinical and Experimental Medicine Section of Paediatrics University of Pisa Pisa Italy
                [ 17 ] Department of Pediatric Pneumology, Immunology and Intensive Care Medicine Charité Medical University Berlin Germany
                [ 18 ] Immunomodulation and Tolerance Group; Allergy and Clinical Immunology Section of Inflammation, Repair and Development National Heart and Lung Institute Imperial College London London UK
                [ 19 ] the MRC & Asthma UK Centre in Allergic Mechanisms of Asthma London UK
                [ 20 ] Allergy and Clinical Immunology National Heart and Lung Institute Imperial College London and Royal Brompton Hospitals NHS Foundation Trust London UK
                [ 21 ] Hans Christian Andersen Children's Hospital Odense University Hospital Odense Denmark
                [ 22 ] Immunomodulation and Tolerance Group, Allergy and Clinical Immunology Inflammation, Repair and Development National Heart and Lung Institute Asthma UK Centre in Allergic Mechanisms of Asthma Imperial College London London UK
                [ 23 ] Aziz Sancar Institute of Experimental Medicine Department of Immunology Istanbul University Istanbul Turkey
                [ 24 ] The Referral Centre for Food Allergy Diagnosis and Treatment Veneto Region Department of Women and Child Health University of Padua Padua Italy
                [ 25 ] Institute of Child Health Department of Pediatric Basic Sciences Istanbul University Istanbul Turkey
                [ 26 ] Faculty of Medicine Department of Pediatrics Division of Pediatric Allergy and Immunology Istanbul University Istanbul Turkey
                [ 27 ] Department of Pediatrics Allergy Unit University of Messina Messina Italy
                [ 28 ] Department of Otorhinolaryngology, Head and Neck Surgery Section of Rhinology and Allergy University Hospital Marburg, Philipps‐Universität Marburg Marburg Germany
                [ 29 ] NIHR Biomedical Research Centre University Hospital Southampton NHS Foundation Trust Southampton UK
                [ 30 ] Faculty of Medicine University of Southampton Southampton UK
                [ 31 ] Department of Dermatology and Venerology Medical University of Graz Graz Austria
                [ 32 ] Allergy Outpatient Clinic Reumannplatz Vienna Austria
                [ 33 ] Department of Paediatrics Imperial College London London UK
                Article
                PAI13189
                10.1111/pai.13189
                7317851
                32436290
                30b8f77a-7d0d-4521-b715-17198d5438d4
                © 2020 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Page count
                Figures: 18, Tables: 16, Pages: 101, Words: 76575
                Categories
                EAACI Allergen Immunotherapy User's Guide
                EAACI Allergen Immunotherapy User's Guide
                Custom metadata
                2.0
                May 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:26.06.2020

                Pediatrics
                allergy,immune regulation,immunotherapy,tolerance
                Pediatrics
                allergy, immune regulation, immunotherapy, tolerance

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