Clinical and Experimental Allergy最新文献

Introduction: Jack Jumper ant (JJA) venom immunotherapy (VIT) is highly efficacious but the lowest effective dose is unknown. Delta-inulin adjuvant (Advax) is known to enhance honeybee VIT immunogenicity.

Objective: This phase 1/2 single-blind, randomised controlled trial aimed to compare the efficacy and safety of JJA VIT with different doses of venom ± Advax.

Methods: Adults aged 18-65 with a history of immediate systemic reaction (SR) to JJA stings were randomised to receive JJA VIT at a maintenance dose of 25 mcg or 50 mcg ± Advax; participants were blinded to treatment allocation. Primary outcomes were the response to sting challenges after 12 months and venom-specific IgE and IgG4 responses to treatment.

Results: Forty-nine of 50 screened subjects met inclusion criteria and were randomised; 44 started treatment (25 mcg n = 12; 25 mcg + Advax n = 13; 50mcg n = 12, 50 mcg + Advax n = 12). Subsequently, two withdrew due to SRs to treatment, and two withdrew due to unrelated factors. The higher JJA venom maintenance dose was associated with reduced likelihood of SRs (OR 0.53 (95% CI, 0.28-0.98)), while Advax did not have an effect (OR 1.17 (95% CI, 0.59-2.32)). Forty proceeded to sting challenge, with six developing SRs. There was no difference between groups for sting challenge outcome (p = 0.98), and the ORs for 25 mcg vs. 50 mcg venom dose (0.89, 95% CI, 0.38-2.09) and Advax vs. no Advax (0.99, 95% CI 0.42-2.33) indicated no effect. There were no differences between groups for venom sIgE (p = 0.78), sIgG4 (p = 0.25), sIgE/IgG4 ratio (p = 0.42), intradermal (p = 0.77), and basophil activation test (BAT) (p = 0.69) responses to treatment. Subjects with high baseline BAT sensitivity, which reduced markedly in response to treatment, were less likely to have a positive sting challenge (p = 0.006).

Conclusion: Challenge outcomes were similar for all groups, with no significant difference found between 25 and 50 mcg maintenance dose or between treatment with and without Advax. Further research of low dose JJA VIT is warranted to confirm its efficacy and tolerability.

Trial registration: NCT03066986.

Background: Peanut (PN) allergy is an IgE-mediated hypersensitivity with a deviated adaptive immune response dominated by IgE-producing B cells and type 2 T cells (Th2). The in vivo immune response upon antigen encounter, for example, after oral food challenge (OFC), has not been investigated over prolonged timeframes.

Methods: Here, we investigated the kinetics of allergen-specific adaptive immune responses in PN-allergic and non-allergic adults before OFC (d0) and thereafter at d7, d14, d21, d28 by determining PN-specific CD40L⁺4-1BB⁺ conventional (Tconv) and FoxP3⁺ Helios⁺ CD40L^-4-1BB⁺ regulatory T cells (Treg), Ara h 2-specific B cells and PN-specific sIgE and sIgG4 antibody levels.

Results: In PN-allergic donors, PN sIgE levels increased until d28 after OFC, but to a variable extent. This variability was associated with a differential increase of Ara h 2⁺ B cells at d7, based on which we identified strong and weak responders (SR and WR). SR exhibited a more pronounced increase of PN sIgE, stronger in vivo activation of T and B cells (HLA-DR⁺, Ki-67⁺, CD21^-), as well as prominent induction of the low-affinity IgE receptor CD23 in Ara h 2⁺ B cells. In contrast, WR exhibited strong activation of PN-specific Tregs at d7. At baseline, SR and WR differed regarding Ara h 2⁺ memory B cells and frequencies of Th2 and type 2-driving Helios-expressing PN-specific Tconv. Minor changes in Th1 cells were also observed in non-allergic donors.

Conclusions: Our results indicate differential adaptive immune responses towards OFC in PN-allergic adults. In summary, SR displayed a more allergy-maintaining immune response, while WR displayed a rather suppressive immune response. Underlying responsible factors such as genetics, as well as clinical consequences, will require further investigation in larger cohorts.