Cassard L1, Sperber K1, Buivan TP1, Cotillard A2, Bourdet-Sicard R3, Albert ML1, Mottez E1, Laurent J4, Guinnepain MT4, Daëron M5.
ABSTRACT:
BACKGROUND:
Basophil 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.
OBJECTIVE:
Investigate whether mechanisms that control, positively and negatively, basophil activation, which were unraveled and studied in basophils from normal donors, are functional in allergic patients.
METHODS:
FcεRI 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.
RESULTS:
Patient 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.
CONCLUSION:
Regulatory 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.
