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Immunologic Mechanisms of Short-course of Lolium Perenne Peptide Immunotherapy: A Randomized Double-Blind Placebo-Controlled Trial

Sharif, H; Singh, I; Kouser, L; Mösges, R; Bonny, M-A; Karamani, A; Parkin, RV; ... Shamji, MH; + view all (2019) Immunologic Mechanisms of Short-course of Lolium Perenne Peptide Immunotherapy: A Randomized Double-Blind Placebo-Controlled Trial. Journal of Allergy and Clinical Immunology , 144 (3) pp. 738-749. 10.1016/j.jaci.2019.02.023. Green open access

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Abstract

Background Three-week, short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with/without asthma over 4 physician visits is safe, well-tolerated and effective. Objective To investigate immunologic mechanisms of LPP immunotherapy in a subset of patients who participated in a Phase III, multicenter, randomized, double-blind, placebo-controlled trial (clinical.gov NCT02560948). Methods Participants were randomized to receive LPP (n=21) or placebo (PL; n=11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T and B cell responses were evaluated before (V2), end of treatment (V6) and after the pollen season (V8). Results Combined symptom and rescue medication scores (CSMS) were lower during the peak (-35.1%, P=.03) and throughout pollen season (-53.7%, P=.03) in LPP- compared to PL-treated group. CD63+ and CD203cbrightCRTH2+basophils were decreased following LPP treatment at V6 (all, P<.0001) and V8 (all, P<.001), compared to V2. No change in PL-treated group was observed. Blunting of seasonal increases of grass pollen-specific IgE was observed in LPP- but not PL-treated group. LPP immunotherapy but not PL was associated with a reduction of IL-4+ Th2 (V6, P=.02), IL-4+ (V6, P=.001;V8, P=.0095) and IL-21+ (V6, P=.0002) T follicular helper cells. Induction of FoxP3+, follicular regulatory T and IL-10+ Breg cells were observed at V6 (all, P<.05) and V8 (all, P<.05) in LPP-treated group. Induction of regulatory B cells was associated with allergen neutralizing IgG4 blocking antibodies. Conclusion For the first time, we demonstrate that the immunological mechanisms of LPP immunotherapy are underscored by immune modulation in the T and B cell compartments which is necessary for its effect.

Type: Article
Title: Immunologic Mechanisms of Short-course of Lolium Perenne Peptide Immunotherapy: A Randomized Double-Blind Placebo-Controlled Trial
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jaci.2019.02.023
Publisher version: https://doi.org/10.1016/j.jaci.2019.02.023
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Allergy, peptide immunotherapy, T follicular helper cells, Tregs, Bregs
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10071037
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