D2.207 - Early serum IL-6 induction and delayed IL-17A suppression characterise wasp venom allergen-specific immunotherapy

Allergen-specific immunotherapy (AIT) for Hymenoptera venom allergy is highly effective in inducing long-term immune tolerance, however, the underlying immunological mechanisms remain incompletely understood. Biomarkers reflecting tolerance induction are currently lacking and clinical monitoring largely relies on sting challenge. IL-6 and IL-17A have been implicated for immunomodulation during AIT, however, data on longitudinal dynamics remain limited. While suppression of IL-17A has been reported in AIT for allergic rhinitis, corresponding data for venom AIT are currently lacking.

In a prospective exploratory cohort study, ten adult patients (7 female, 3 male; median age 56 (range: 26-69) years) with a confirmed diagnosis of wasp venom allergy were included. Blood samples were collected at four predefined time points during AIT: at baseline, following completion of the inpatient updosing phase, at late follow-up (6-18 months after therapy initiation, immediately prior to sting challenge) and one day post sting challenge. Serum biomarkers were quantified using a multiplex proximity extension assay, allowing simultaneous measurement of 45 cytokines.

Longitudinal analysis revealed a transient, early moderate increase in IL-6 serum levels during AIT updosing (median difference +11.67 pg/mL, p = 0.002) and after sting challenge (median difference +1.77 pg/mL, p = 0.006). In contrast, IL-17A serum levels decreased during AIT maintenance from baseline to follow-up before sting challenge (median difference -0.14 pg/mL, p = 0.027). Additionally, AIT led to an immunomodulation with significant changes also in several other inflammatory mediators, including IL-7, CSF3, CCL7, CCL19, EGF, HGF, MMP12 and OLR1 and a trend towards increases in IL-2 and IL-10. 

Our findings demonstrate dynamic, time-dependent changes of key cytokines during Hymenoptera venom AIT. The early transient increase of IL-6 may reflect an early-stage molecular switch during AIT, which may shift Th2 immune responses towards tolerance induction. Given the association of IL-17A with type-3 inflammatory pathways, the delayed reduction of IL-17A suggests a long-term attenuation of pro-inflammatory immune signaling.