title: Suppression of the immunologic response to peanut during immunotherapy is often transient.
abstract: BACKGROUND
  Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood.
  
  
  OBJECTIVE
  We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy.
  
  
  METHODS
  Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)-T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry.
  
  
  RESULTS
  Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite-induced expression of TH2 cytokines was reduced in DC-T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC-T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy.
  
  
  CONCLUSIONS
  OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and TH2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Mark
authors.initials: M
authors.lastname: Gorelik
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology and Infectious Diseases, University of Medicine and Dentistry of New Jersey, Newark, NJ.
authors.forename: Satya D
authors.initials: SD
authors.lastname: Narisety
authors.affiliation: Department of Pediatrics, Division of Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Guerrerio
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Chichester
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Keet
authors.affiliation: Department of Medicine, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Anja P
authors.initials: AP
authors.lastname: Bieneman
authors.affiliation: Department of Medicine, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wood
authors.affiliation: Department of Medicine, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: John T
authors.initials: JT
authors.lastname: Schroeder
authors.affiliation: Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: pamela.guerrerio@nih.gov.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Frischmeyer-Guerrerio
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D010367:Arachis / Q000009:adverse effects; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D003888:Desensitization, Immunologic; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D021183:Peanut Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060149:Tetraspanin 30 / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D006684:HLA-DR Antigens; D060149:Tetraspanin 30; D015847:Interleukin-4
keywords: Peanut allergy; basophil activation; dendritic cells; food allergy; oral immunotherapy; sublingual immunotherapy; sustained unresponsiveness