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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:135

Article

Gorelik, Mark¹  Narisety, Satya D.⁴  Guerrerio, Anthony L.³  Chichester, Kristin L.¹  Keet, Corinne A.¹  Bieneman, Anja P.²  Hamilton, Robert G.²  Wood, Robert A.¹  Schroeder, John T.²  Frischmeyer-Guerrerio, Pamela A.¹ 

[1] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Immunol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Gastroenterol & Nutr, Baltimore, MD 21205 USA

[4] Univ Med & Dent New Jersey, Dept Pediat, Div Allergy Immunol & Infect Dis, Newark, NJ 07103 USA

关键词: Peanut allergy;    oral immunotherapy;    sublingual immunotherapy;    sustained unresponsiveness;    basophil activation;    dendritic cells;    food allergy;   

DOI  :  10.1016/j.jaci.2014.11.010

来源: Elsevier

【 摘 要 】

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 T(H)2 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: OITand 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.

【 授权许可】

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