Early decrease in basophil sensitivity to Ara h 2 precedes sustained unresponsiveness after peanut oral immunotherapy - 05/11/19
, Johanna Steinbrecher, BS a, Agustin Calatroni, MS e, Neal Smith, MS a, Alex Ma, BS a, Bert Ruiter, PhD a, b, c, d, Yamini Virkud, MD, MPH a, b, d, Michael Schneider, BS f, Wayne G. Shreffler, MD, PhD a, b, c, dAbstract |
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 CD63hi 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Basophil activation, immunotherapy, immunoglobulin, oral immunotherapy, food allergy, peanut allergy, Ara h 2, IgE, IgG4
Abbreviations used : AUC, ED50, OIT, SU, TD
Plan
| This work was supported by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (grant K23AI121491 to S.U.P.); the American Academy of Allergy, Asthma & Immunology/Food Allergy Research Education; the 2012 Howard Gittis Memorial 3rd/4th Year Fellowship/New Faculty Research Award (to S.U.P.), and research support from BÜHLMANN Laboratories AG (to W.G.S.). The clinical trial work was performed in the Harvard Clinical and Translational Science Center supported by grants 1UL1TR001102 and 8UL1TR000170 from the National Center for Advancing Translational Sciences and 1UL1 RR025758 from the National Center for Research Resources. Cytometry performed in the MGH Department of Pathology Flow and Image Cytometry Research Core was supported by the NIH Shared Instrumentation program with grants 1S10OD012027-01A1, 1S10OD016372-01, 1S10RR020936-01, and 1S10RR023440-01A1. |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 144 - N° 5
P. 1310 - novembre 2019 Retour au numéro
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