Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:144

Article

Patil, Sarita U.^1,2,3,4  Steinbrecher, Johanna¹  Calatroni, Agustin⁵  Smith, Neal¹  Ma, Alex¹  Ruiter, Bert^1,2,3,4  Virkud, Yamini^1,2,4  Schneider, Michael⁶  Shreffler, Wayne G.^1,2,3,4 

[1] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA

[2] Harvard Med Sch, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[4] Broad Inst MIT & Harvard, Food Allergy Sci Initiat, Boston, MA USA

[5] Rho, Chapel Hill, NC USA

[6] BUHLMANN Labs, Schonenbuch, Switzerland

关键词: Basophil activation;    immunotherapy;    immunoglobulin;    oral immunotherapy;    food allergy;    peanut allergy;    Ara h 2;    IgE;    IgG(4);   

DOI  :  10.1016/j.jaci.2019.07.028

来源: Elsevier

【 摘 要 】

Background: Only some patients with peanut allergy undergoing oral immunotherapy (OIT) achieve sustained clinical response. Basophil activation could provide a functional surrogate of efficacy. Objective: We hypothesized that changes in basophil sensitivity and area under the curve (AUC) to the immunodominant allergen Ara h 2 correlate with clinical responses to OIT. Methods: Children with peanut allergy aged 7 to 13 years were enrolled in a single-center, open-label peanut OIT trial. Levels of specific immunoglobulins were measured throughout OIT. Peripheral blood from multiple time points was stimulated in vitro with peanut allergens for flow cytometric assessment of the percentage of CD63(hi) activated basophils. Results: Twenty-two of 30 subjects were successfully treated with OIT; after avoidance, 9 achieved sustained unresponsiveness (SU), and 13 had transient desensitization (TD). Basophil sensitivity, measured by using the dose that induces 50% of the maximal basophil response, to Ara h 2 stimulation decreased from baseline in subjects with SU (after OIT, P = .0041; after avoidance, P = .0011). At 3 months of OIT, basophil sensitivity in subjects with SU decreased from baseline compared with that in subjects with TD (median, 18-fold vs 3-fold; P = .01), with a receiver operating characteristic of 0.84 and optimal fold change of 4.9. Basophil AUC to Ara h 2 was suppressed after OIT equally in subjects with SU and those with TD (P = .4). After avoidance, basophil AUC rebounded in subjects with TD but not those with SU (P < .001). Passively sensitized basophils suppressed with postavoidance SU plasma had a lower AUC than TD plasma (6.4% vs 38.9%, P = .03). Conclusions: Early decreases in basophil sensitivity to Ara h 2 correlate with SU. Basophil AUC rebounds after avoidance in subjects with TD. Therefore, different aspects of basophil activation might be useful for monitoring of OIT efficacy.

【 授权许可】

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