Allergen Inflammation After Prior Exposure to House Dust Mite

Total Page:16

File Type:pdf, Size:1020Kb

Allergen Inflammation After Prior Exposure to House Dust Mite Rhinovirus Infection Promotes Eosinophilic Airway Inflammation after Prior Exposure to House Dust Mite Allergen Downloaded from Amit K. Mehta and Michael Croft ImmunoHorizons 2020, 4 (8) 498-507 doi: https://doi.org/10.4049/immunohorizons.2000052 http://www.immunohorizons.org/content/4/8/498 http://www.immunohorizons.org/ This information is current as of September 26, 2021. Supplementary http://www.immunohorizons.org/content/suppl/2020/08/13/4.8.498.DCSupp Material lemental References This article cites 35 articles, 12 of which you can access for free at: http://www.immunohorizons.org/content/4/8/498.full#ref-list-1 by guest on September 26, 2021 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://www.immunohorizons.org/alerts ImmunoHorizons is an open access journal published by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. ISSN 2573-7732. RESEARCH ARTICLE Infectious Disease Rhinovirus Infection Promotes Eosinophilic Airway Inflammation after Prior Exposure to House Dust Mite Allergen Amit K. Mehta,*,1 and Michael Croft*† *Center for Autoimmunity and Inflammation, La Jolla Institute for Immunology, La Jolla, CA 92037; and †Department of Medicine, University of California, San Diego, La Jolla, CA 92093 Downloaded from ABSTRACT Respiratory virus infection normally drives neutrophil-dominated airway inflammation, yet some viral infections result in an http://www.immunohorizons.org/ eosinophil-dominated response in individuals such as allergic asthmatics. One idea is that viral infection simply exacerbates an ongoing type 2 response to allergen. However, prior exposure to allergen might alter the virus-induced innate response such that type 2–like eosinophilic inflammation can be induced. To test this, mice were sensitized intranasally with house dust mite allergen and then at later times exposed to rhinovirus RV1B via the airways. RV1B infection of naive mice led to the expected neutrophilic lung inflammatory response with no eosinophils or mucus production. In contrast, if mice were exposed to RV1B 1–4 wk after house dust mite inhalation, when the allergen response had subsided, infection led to eosinophilia and mucus production and a much stronger lymphocyte response that were partially or fully steroid resistant. In accordance, RV1B infection resulted in elevated expression of several inflammatory factors in allergen–pre-exposed mice, specifically those associated with type 2 immunity, namely CCL17, CXCL1, CCL2, IL-33, and IL-13. In vitro studies further showed that RV infection led to greater production of chemokines and cytokines in human bronchial epithelial cells that were previously stimulated with allergen, reinforcing the notion of an altered virus by guest on September 26, 2021 response after allergen exposure. In conclusion, we report that prior allergen exposure can modify responsiveness of cells in the lungs such that a qualitatively and quantitatively different inflammatory activity results following virus infection that is biased toward type 2–like airway disease. ImmunoHorizons, 2020, 4: 498–507. INTRODUCTION Cold viruses might drive this type of response, including rhinovirus (RV) (1–5). Typical of most viruses, RVs largely result There is considerable interest in the inflammatory response to in a neutrophil-dominated innate inflammatory response post- viruses that infect the respiratory tract. Most viruses are thought infection, with little or no signs of type 2 immunity, such as mucus to drive a type 1/17–like immune response, resulting in lung production or infiltration of eosinophils into the lungs. Thus, what neutrophilia; however, a number of viral respiratory tract dictates the induction of a neutrophilic versus eosinophilic infections have been linked to type 2–like inflammation typical response is not clear. A number of studies have tried to address of asthma. It has been suggested that viral infections may cause up this in mouse models with coexposure to RV and allergen at the to 90% of asthma-like symptoms in children and 60% in adults. same time. In some studies, with house dust mite (HDM) allergen, Received for publication June 16, 2020. Accepted for publication July 28, 2020. Address correspondence and reprint requests to: Prof. Michael Croft, Division of Immune Regulation, La Jolla Institute for Immunology, 9420 Athena Circle, La Jolla, CA 92037. E-mail address: [email protected] ORCID: 0000-0002-6062-3635 (M.C.). 1Current address: Fate Therapeutics, La Jolla, CA. This work was supported by National Institutes of Health Grant AI070535 (to M.C.). A.K.M. performed experiments. M.C. and A.K.M. wrote the manuscript. Abbreviations used in this article: BAL, bronchoalveolar lavage; DC, dendritic cell; HDM, house dust mite; i.n., intranasal, intranasally; PAS, periodic acid–Schiff; RV, rhinovirus. The online version of this article contains supplemental material. This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license. Copyright © 2020 The Authors 498 https://doi.org/10.4049/immunohorizons.2000052 ImmunoHorizons is published by The American Association of Immunologists, Inc. ImmunoHorizons RHINOVIRUS INDUCES ALLERGIC LUNG INFLAMMATION 499 the investigators failed to demonstrate enhancement of type 2 Institute for Immunology Animal Care Committee in accordance inflammation upon concomitant airway exposure to RV; however, with guidelines of the Association for the Assessment and they did find an increased neutrophil response characteristic of Accreditation of Laboratory Animal Care. that which can be induced by RV infection alone (6–8). Alternatively, other studies found that RV infection given at the RV generation and experimental protocols same time as the model allergen OVA or HDM, or 1 d later, led to RV1B stocks were generated as described elsewhere (16). For enhanced lung infiltration of eosinophils, augmented mucus allergen experiments, mice were sensitized intranasally (i.n.) with production, and an overall greater type 2 response than driven 50 mg of HDM extract (Greer Labs, Lenoir, NC) given on days 0, 1, by the allergen alone (9–14). The disparity between these results is 7, and 8 and then challenged acutely with 25 mg of HDM given on not clear but could be due to the dose of allergen and strength of days 21, 22, and 23. Twelve or fourteen days or 4 wk later, mice response to the allergen, the content of LPS in the allergen that, were either exposed to PBS or infected with 50 mlofRV1B(;5 3 normally, at high levels promotes type 1/17 immunity or the 107 PFU/ml) given i.n. Mice were sacrificed 24 h after the infection amount of virus used. Regardless, in either case, the data implied for all analyses. For studies with steroid treatment, mice were that infection acted through amplifying the production of type 1/17 sensitized and challenged with HDM as above and either received or type 2 inflammatory mediators in the lungs induced by the PBS or dexamethasone (Sigma-Aldrich) i.n. at 0.5 mg/kg of body Downloaded from allergen. weight in a volume of 50 ml, 30–60 min before the RV1B challenge. An alternative mechanism is also possible to explain a link For some experiments, RV1B was inactivated by exposure to UV between type 2 lung inflammation and virus infection, although at light for 20 min immediately before infection. In other experi- present underexplored. In this scenario, prior allergen exposure ments, mice were sensitized and challenged with HDM as above, could transiently or permanently alter the infectivity of lung with coexposure to PBS or RV1B given i.n. on the same day as the http://www.immunohorizons.org/ epithelialcellsorotherlungcellsbythevirusorcouldaltertheir last challenge with HDM. responsiveness to viral danger signals such that the virus infection alone triggers a response that resembles that normally induced by Bronchoalveolar lavage analysis and lung histology allergen. Along these lines, one publication found that mice that Bronchoalveolar lavage (BAL) was performed 24 h after the RV1B were repeatedly challenged with pneumonia virus and cockroach challenge. BAL fluid was examined for cellular content. BAL cells allergen subsequently displayed both lung eosinophilia and were counted, and BAL cell differentials were determined using neutrophilia and epithelial cell mucus secretion when infected flow cytometry based on cell surface markers. BAL cells were with RV 1 mo later (15). In this study, we present experimental preincubated with mouse Fc-blocking Ab (2.4G2) and then stained evidence in the mouse that supports these data and furthers the with fluorochrome-conjugated Abs (all from BD Biosciences, La idea that prior allergen exposure can modify the airway response Jolla, CA) to Siglec F (PE), Ly-6C (FITC), Gr-1 (APC), CD11b (PE- by guest on September 26, 2021 to virus. Whereas RV infection of naive mice resulted in airway Cy7), CD11c (eFluor 450), and CD45 (PerCp-Cy5.5) for 20 min at neutrophilia without significant eosinophilia or mucus production, 4°C.SampleswereanalyzedonanLSRIIflow cytometer and infection of mice .1wkandupto4wkaftertheywereexposedto FlowJo software. Part of the lung tissue was kept in RNAlater HDM allergen resulted in strong eosinophilia and mucus pro- solution (Invitrogen, San Diego, CA) for RNA isolation. For lung duction together with neutrophilia and an overall larger lung histology, 5–6-mm sections were cut and stained with H&E for inflammatory response. These data correlated with greater examining cell infiltration and
Recommended publications
  • Food Allergy Outline
    Allergy Evaluation-What it all Means & Role of Allergist Sai R. Nimmagadda, M.D.. Associated Allergists and Asthma Specialists Ltd. Clinical Assistant Professor Of Pediatrics Northwestern University Chicago, Illinois Objectives of Presentation • Discuss the different options for allergy evaluation. – Skin tests – Immunocap Testing • Understand the results of Allergy testing in various allergic diseases. • Briefly Understand what an Allergist Does Common Allergic Diseases Seen in the Primary Care Office • Atopic Dermatitis/Eczema • Food Allergy • Allergic Rhinitis • Allergic Asthma • Allergic GI Diseases Factors that Influence Allergies Development and Expression Host Factors Environmental Factors . Genetic Indoor allergens - Atopy Outdoor allergens - Airway hyper Occupational sensitizers responsiveness Tobacco smoke . Gender Air Pollution . Obesity Respiratory Infections Diet © Global Initiative for Asthma Why Perform Allergy Testing? – Confirm Allergens and answer specific questions. • Am I allergic to my dog? • Do I have a milk allergy? • Have I outgrown my allergy? • Do I need medications? • Am I penicillin allergic? • Do I have a bee sting allergy Tests Performed in the Diagnostic Allergy Laboratory • Allergen-specific IgE (over 200 allergen extracts) – Pollen (weeds, grasses, trees), – Epidermal, dust mites, molds, – Foods, – Venoms, – Drugs, – Occupational allergens (e.g., natural rubber latex) • Total Serum IgE (anti-IgE; ABPA) • Multi-allergen screen for IgE antibody Diagnostic Allergy Testing Serological Confirmation of Sensitization History of RAST Testing • RAST (radioallergosorbent test) invented and marketed in 1974 • The suspected allergen is bound to an insoluble material and the patient's serum is added • If the serum contains antibodies to the allergen, those antibodies will bind to the allergen • Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material • The unbound anti-human IgE antibodies are washed away.
    [Show full text]
  • Allergen Regulations 105 Cmr 590.000
    ALLERGEN REGULATIONS 105 CMR 590.000: STATE SANITARY CODE CHAPTER X – MINIMUM SANITATION STANDARDS FOR FOOD ESTABLISHMENTS (1) ADD new definition in 105 CMR 590.002(B): Major Food Allergen means: (1) Milk, eggs, fish (such as bass, flounder, or cod), crustaceans (such as crab, lobster, or shrimp), tree nuts (such as almonds, pecans, or walnuts), wheat, peanuts, and soybeans; and (2) A FOOD ingredient that contains protein derived from a FOOD named in subsection (1). "Major food allergen" does not include: (a) Any highly refined oil derived from a FOOD specified in subsection (1) or any ingredient derived from such highly refined oil; or (b) Any ingredient that is exempt under the petition or notification process specified in the federal Food Allergen Labeling and Consumer Protection Act of 2004 (Public Law 108-282). (2) Amend the definitions of “menu” and “menu board” in 590.002(B) as follows: Menu means a printed list or pictorial display of a food item or items and their price(s) that are available for sale from a food establishment, and includes menus distributed or provided outside of the establishment. Menu Board means any list or pictorial display of a food item or items and their price(s) posted within or outside a food establishment. (3) Amend as follows 105 CMR 590.003(B) (Management and Personnel – federal 1999 Food Code Chapter 2) (B) FC 2-102.11 Demonstration … The areas of knowledge include: . (17) No later than February 1, 2011: (a) Describing FOODS identified as MAJOR FOOD ALLERGENS and describing the symptoms that MAJOR FOOD ALLERGENS could cause in a sensitive individual who has an allergic reaction; and (b) Ensuring that employees are properly trained in food allergy awareness as it relates to their assigned duties.
    [Show full text]
  • Food Allergen Labeling Exemption Petitions and Notifications: Guidance for Industry
    Contains Nonbinding Recommendations Food Allergen Labeling Exemption Petitions and Notifications: Guidance for Industry Additional copies are available from: Office of Food Additive Safety, HFS-205 Center for Food Safety and Applied Nutrition Food and Drug Administration 5001 Campus Drive College Park, MD 20740 (Tel) 240-402-1200 http://www.fda.gov/FoodGuidances You may submit either electronic or written comments regarding this guidance at any time. Submit electronic comments to http://www.regulations.gov. Submit written comments on the guidance to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register. U.S. Department of Health and Human Services Food and Drug Administration Center for Food Safety and Applied Nutrition June 2015 Petitions and Notifications Guidance Page 1 of 18 Contains Nonbinding Recommendations Table of Contents I. Introduction II. Statutory Authority III. Recommendations for Preparing Submissions IV. Additional Information for Petitions V. Additional Information for Notifications VI. Appendices Petitions and Notifications Guidance Page 2 of 18 Contains Nonbinding Recommendations Food Allergen Labeling Exemption Petitions and Notifications Guidance for Industry This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.
    [Show full text]
  • An Update on Food Allergen Management and Global Labeling
    An Update on Food Allergen Management and Global Labeling Regulations A Thesis SUBMITTED TO THE FACULTY OF UNIVERSITY OF MINNESOTA BY Xinyu Diao IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE Advisor: David Smith, Ph.D. Aug 2017 © {Xinyu Diao} {2017} Acknowledgements I would like to thank my advisor Dr. David Smith for his guidance and support throughout my Master’s program. With his advice to join the program, my wonderful journey at the University of Minnesota began. His tremendous support and encouragement motivates me to always dream big. I would like to also thank Dr. Jollen Feritg, Dr. Len Marquart and Dr. Adam Rothman for being willing to take their valuable time to serve as my committee members. I am grateful to many people whose professional advice is invaluable over the course of this project. I would like to take this opportunity to show appreciation for Dr. Gerald W. Fry for being a role model for me as having lifetime enthusiasm for the field you study. I wouldn’t be where I am now without the support of my friends. My MGC (Graduate Student Club) friends who came all around the world triggered my initial interest to investigate a topic which has been concerned in a worldwide framework. Finally, I would like to give my most sincere gratitude to my family, who provide me such a precious experience of studying abroad and receiving superior education. Thank you for your personal sacrifices and tremendous support when I am far away from home. i Dedication I dedicate this thesis to my father, Hongquan Diao and my mother, Jun Liu for their unconditional love and support.
    [Show full text]
  • Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity
    Polish J. of Environ. Stud. Vol. 18, No 3 (2009), 325-330 Review Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity E. Kucharska1*, J. Bober2**, L. Jędrychowski3*** 1Department of Human Nutrition, Faculty of Food Sciences and Fisheries, West-Pomeranian University of Technology, Papieża Pawła VI no. 3, 71-459 Szczecin, Poland 2Department of Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland 3Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn, Tuwima 10, 10-747 Olsztyn, Poland Received: 7 July 2008 Accepted: 11 December 2008 Abstract The environment is used as a broad umbrella term for all sources of allergens which may cause allergic hypersensitive reaction of the immune system of humans. Westernization of life leads to increased average consumption of food additives (natural and xenobiotics) – starting from over 5kg (10lbs) annually with a strong tendency to intensify. Modern technologies of food production often employ substances improving quality, texture, colour, taste, acidity or alkalinity. Haptens present in food or drugs, penetrating organism via gastrointestinal tract, may be responsible for symptoms not only in the gastrointestinal tract itself, but also in peripheral organs. Mechanisms of hapten action within human body are different – they include reactions when the immune system is involved (allergic hypersensitivity) and not involved (food intolerance also known as non-allergic hypersensitivity). Food intolerance is a more frequent phenomenon diagnosed in 20-50% of cases; food allergy affecting 6-8% children and 1-2% adults. Our work elucidates mechanisms of hypersensi- tivity responses to haptens, and characterizes major haptens applied as food additives.
    [Show full text]
  • Allergen Testing AHS – G2031
    Corporate Medical Policy Allergen Testing AHS – G2031 File Name: allergen_testing Origination: 01/01/2019 Last CAP Review: 11/2020 Next CAP Review: 11/2021 Last Review: 11/2020 Description of Procedure or Service Allergic disease is characterized by inappropriate or exaggerated immune reactions to foreign antigens (allergens) that are generally innocuous to most people, but when introduced into a genetically-predisposed individual, elicit a hypersensitivity reaction (R. Hamilton, 2020). Hypersensitivity reactions can be classified into four types, two of which are associated with allergy, type I immediate immunoglobulin E (IgE) reactions and type IV T cell mediated reactions (K.-L. Chang & J. C. Guarderas, 2018). Type I reactions involve the formation of IgE antibodies specific to the allergen. When the subject is re-exposed to that allergen, the allergen binds multiple IgE molecules, resulting in the release of an array of inflammatory mediators, including histamines, that precipitate the symptoms of allergic disease (R. Hamilton, 2018). Allergen testing in serum is designed to detect the presence of allergen-specific IgE. A positive test for allergen-specific IgE confirms the presence of the antibody only. Actual reactivity must be determined by history or supervised challenge (Kowal & DuBuske, 2020). Several diagnostic procedures have been developed to elicit and assess hypersensitivity reactions including epicutaneous, intradermal, patch, bronchial, exercise, and ingestion challenge tests (Bernstein et al., 2008). ***Note: This Medical Policy is complex and technical. For questions concerning the technical language and/or specific clinical indications for its use, please consult your physician. Policy BCBSNC will provide coverage for allergen testing when it is determined the medical criteria or reimbursement guidelines below are met.
    [Show full text]
  • Tolerance to Allergens: How It Develops and How It Can Be Induced
    Session 2101 Plenary: Immunotherapy: Mechanism, Outcomes and Markers Tolerance to Allergens: How it Develops and How it Can be Induced Cezmi A. Akdis, MD Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland Corresponding author: Cezmi A. Akdis, MD Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos Address E-mail: [email protected] Tel.: + 41 81 4100848 Fax: + 41 81 4100840 Acknowledgments: The authors' laboratories are supported by the Swiss National Foundation grant 320030_132899 and Christine Kühne Center for Allergy Research and Education (CK-CARE). ABSTRACT The induction of immune tolerance and specific immune suppression are essential processes in the control of immune responses. Allergen immunotherapy induces early desensitization and peripheral T cell tolerance to allergens associated with development of Treg and Breg cells, and downregulation of several allergic and inflammatory aspects of effector subsets of T cells, B cells, basophils, mast cells and eosinophils. Similar molecular and cellular mechanisms have been observed in subcutaneous and sublingual AIT as well as natural tolerance to high doses of allergen exposure. In allergic disease, the balance between allergen-specific Treg and disease-promoting T helper 2 cells (Th2) appears to be decisive in the development of an allergic versus a non-disease promoting or “healthy” immune response against allergen. Treg specific for common environmental allergens represent the dominant subset in healthy individuals arguing for a state of natural tolerance to allergen in these individuals. In contrast, there is a high frequency of allergen-specific Th2 cells in allergic individuals. Treg function appears to be impaired in active allergic disease.
    [Show full text]
  • Allergen-Specific Immunoglobulin E Antibodies in Wheezing Infants: the Risk for Asthma in Later Childhood
    Allergen-Specific Immunoglobulin E Antibodies in Wheezing Infants: The Risk for Asthma in Later Childhood Anne Kotaniemi-Syrja¨nen, MD*; Tiina M. Reijonen, MD*; Jarkko Romppanen, MD‡; Kaj Korhonen, MD*; Kari Savolainen, PhD‡; and Matti Korppi, MD* ABSTRACT. Objective. To evaluate whether the mea- predictive value; LRϩ, positive likelihood ratio; ROC, receiver surement of specific immunoglobulin E (IgE) antibodies operating characteristic. to food and/or inhalant allergens in infants who are hospitalized for wheezing can be used to predict later pproximately 20% of all children experience asthma. 1 Methods. Eighty-two children who were hospitalized wheezing in infancy, and these children are for wheezing at <2 years of age were followed prospec- Aat increased risk for asthma in later child- tively until early school age. The baseline data and the hood. On the basis of recent prospective follow-up characteristics of infancy had been collected at enroll- data, up to 40% of them experience asthma at school ment. At school age, the children were evaluated for age.2 The majority of children with asthma have asthma and allergic manifestations, including skin prick clinically evident atopic manifestations in later child- tests to common inhalant allergens. Frozen serum sam- hood, although allergies may not be apparent in ples obtained during the index episode of wheezing were infancy.2,3 Total serum immunoglobulin E (IgE),2 available for 80 children for determination of food and blood eosinophilia,2 and serum eosinophil cationic inhalant allergen-specific serum IgE antibodies by flu- 4 oroenzyme-immunometric assay, UniCAP, applying the protein (ECP) are markers that are often used to Phadiatop Combi allergen panel.
    [Show full text]
  • Allergen-Induced Eosinophil Trafficking Block 4 Aspirin
    Cutting Edge: Lipoxin (LX) A4 and Aspirin-Triggered 15-Epi-LXA 4 Block Allergen-Induced Eosinophil Trafficking This information is current as Christianne Bandeira-Melo, Patricia T. Bozza, Bruno L. of September 23, 2021. Diaz, Renato S. B. Cordeiro, Peter J. Jose, Marco A. Martins and Charles N. Serhan J Immunol 2000; 164:2267-2271; ; doi: 10.4049/jimmunol.164.5.2267 http://www.jimmunol.org/content/164/5/2267 Downloaded from References This article cites 35 articles, 10 of which you can access for free at: http://www.jimmunol.org/content/164/5/2267.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 23, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. ● Cutting Edge: Lipoxin (LX) A4 and Aspirin-Triggered 15-Epi-LXA4 Block Allergen-Induced Eosinophil Trafficking1 Christianne Bandeira-Melo,* Patricia T. Bozza,2* Bruno L. Diaz,* Renato S.
    [Show full text]
  • Remote Allergen Exposure Elicits Eosinophil Infiltration Into
    www.nature.com/mi ARTICLE Remote allergen exposure elicits eosinophil infiltration into allergen nonexposed mucosal organs and primes for allergic inflammation Courtney L. Olbrich1,2, Maytal Bivas-Benita3, Jason J. Xenakis3, Samuel Maldonado3, Evangeline Cornwell1,4, Julia Fink1,4, Qitong Yuan1,4, Nathan Gill4, Ryan Mansfield1, Karen Dockstader1 and Lisa A. Spencer 1,2,3 The natural history of allergic diseases suggests bidirectional and progressive relationships between allergic disorders of the skin, lung, and gut indicative of mucosal organ crosstalk. However, impacts of local allergic inflammation on the cellular landscape of remote mucosal organs along the skin:lung:gut axis are not yet known. Eosinophils are tissue-dwelling innate immune leukocytes associated with allergic diseases. Emerging data suggest heterogeneous phenotypes of tissue-dwelling eosinophils contribute to multifaceted roles that favor homeostasis or disease. This study investigated the impact of acute local allergen exposure on the frequency and phenotype of tissue eosinophils within remote mucosal organs. Our findings demonstrate allergen challenge to skin, lung, or gut elicited not only local eosinophilic inflammation, but also increased the number and frequency of eosinophils within remote, allergen nonexposed lung, and intestine. Remote allergen-elicited lung eosinophils exhibited an inflammatory phenotype and their presence associated with enhanced susceptibility to airway inflammation induced upon subsequent inhalation of a different allergen. These data demonstrate,
    [Show full text]
  • Basophil Activation Test
    Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice Alexandra Santos1,1, Oral Alpan2, and Hans J¨urgenHoffmann3 1King's College London 2O&O ALPAN 3Aarhus University Hospital July 16, 2020 Abstract The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry and is directly correlated with histamine release. From the bell-shaped curve resulting from BAT in allergic patients, basophil reactivity (given by %CD63+ basophils) and basophil sensitivity (given by EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype, it can potentially be used to monitor the natural resolution of food allergies and to predict and monitor clinical response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for certification. Basophil
    [Show full text]
  • Influence of Antihistamines on Basophil Activation Test in Food
    diagnostics Article Influence of Antihistamines on Basophil Activation Test in Food Allergy to Milk and Egg Eleonora Nucera 1,†, Riccardo Inchingolo 2,*,† , Rosario Nicotra 3 , Manuela Ferraironi 3, Anna Giulia Ricci 4, Giuseppe Parrinello 4 , Marilena La Sorda 3, Maurizio Sanguinetti 5, Antonio Gasbarrini 6 and Angela Rizzi 4 1 UOSD Allergologia e Immunologia Clinica, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; [email protected] 2 UOC Pneumologia, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy 3 UOC Microbiologia, Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; [email protected] (R.N.); [email protected] (M.F.); [email protected] (M.L.S.) 4 UOSD Allergologia e Immunologia Clinica, Dipartimento Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Roma, Italy; [email protected] (A.G.R.); [email protected] (G.P.); [email protected] (A.R.) 5 UOC Microbiologia, Dipartimento Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Roma, Italy; [email protected]
    [Show full text]