Suppression of the immunologic response to peanut during immunotherapy is often transient

Mark Gorelik, Satya D. Narisety, Anthony L Guerrerio, Kristin L. Chichester, Corinne Keet, Anja P. Bieneman, Robert G Hamilton, Robert A Wood, John Thomas Schroeder, Pamela A. Frischmeyer-Guerrerio

Research output: Contribution to journalArticle

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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1283-1292
Number of pages10
JournalThe Journal of Allergy and Clinical Immunology
Volume135
Issue number5
DOIs
StatePublished - May 1 2015

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Immunotherapy
Sublingual Immunotherapy
Dendritic Cells
Basophils
Coculture Techniques
Cytokines
T-Lymphocytes
Interleukin-4
Allergens
Flow Cytometry
Peanut Hypersensitivity
Fluorometry
Food Hypersensitivity
Arachis
Histamine Release
Mites
HLA-DR Antigens
Myeloid Cells
Dust
Histamine

Keywords

  • basophil activation
  • dendritic cells
  • food allergy
  • oral immunotherapy
  • Peanut allergy
  • sublingual immunotherapy
  • sustained unresponsiveness

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Suppression of the immunologic response to peanut during immunotherapy is often transient. / Gorelik, Mark; Narisety, Satya D.; Guerrerio, Anthony L; Chichester, Kristin L.; Keet, Corinne; Bieneman, Anja P.; Hamilton, Robert G; Wood, Robert A; Schroeder, John Thomas; Frischmeyer-Guerrerio, Pamela A.

In: The Journal of Allergy and Clinical Immunology, Vol. 135, No. 5, 01.05.2015, p. 1283-1292.

Research output: Contribution to journalArticle

Gorelik, Mark ; Narisety, Satya D. ; Guerrerio, Anthony L ; Chichester, Kristin L. ; Keet, Corinne ; Bieneman, Anja P. ; Hamilton, Robert G ; Wood, Robert A ; Schroeder, John Thomas ; Frischmeyer-Guerrerio, Pamela A. / Suppression of the immunologic response to peanut during immunotherapy is often transient. In: The Journal of Allergy and Clinical Immunology. 2015 ; Vol. 135, No. 5. pp. 1283-1292.
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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. Conclusion 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.",
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AU - Gorelik, Mark

AU - Narisety, Satya D.

AU - Guerrerio, Anthony L

AU - Chichester, Kristin L.

AU - Keet, Corinne

AU - Bieneman, Anja P.

AU - Hamilton, Robert G

AU - Wood, Robert A

AU - Schroeder, John Thomas

AU - Frischmeyer-Guerrerio, Pamela A.

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N2 - 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. Conclusion 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.

AB - 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. Conclusion 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.

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