Basophils from allergic patients are neither hyper-responsive to activation signals nor hypo-responsive to inhibition signals

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Lydie Cassard, Katia Sperber, Tan-Phuc Buivan, Aurélie Cotillard, Raphaëlle Bourdet-Sicard, Matthew L. Albert, Estelle Mottez, Jérôme Laurent, Marie-Thérèse Guinnepain, Marc Daëron
BackgroundBasophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals upon aggregation, whose ratio depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (FcγRIIA/B) generate inhibition signals when co-engaged with FcεRI by allergen-antibody immune complexes. Commensal and probiotic bacteria such as L. paracasei generate inhibition signals by still unclear mechanisms.ObjectiveInvestigate whether mechanisms that control, positively and negatively, basophil activation, which were unraveled and studied in basophils from normal donors, are functional in allergic patients.MethodsFcεRI and FcγRIIA/B expression, FcεRI-dependent activation, FcεRI-dependent inhibition, and FcγRIIB-dependent inhibition were examined in blood basophils incubated overnight with L. paracasei or without, and challenged under 10 experimental conditions. Basophils from normal donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis.ResultsPatient basophils expressed neither more FcεRI nor less FcγRIIB than basophils from normal donors. They were neither hyper-reactive to positive regulation nor hypo-reactive to negative regulation, whatever the receptors or the mechanisms involved and whatever the allergic manifestations patients suffered from.ConclusionRegulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestation. Based on these mechanisms, "immune checkpoint modifiers" can be developed as novel therapeutic tools for allergy.

Teaser

Basophils from allergic patients are neither hyper-responsive to IgE-induced activation nor hypo-responsive to IgG- and/or lactobacilli-induced inhibition. Mechanisms that control basophil activation can therefore be used as therapeutic tools in allergic diseases.


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