Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial
Hanisah Sharif, Iesha Singh, Lubna Kouser, Ralph Mösges, Marie-Alix Bonny, Angeliki Karamani, Rebecca V Parkin, Nicolas Bovy, Uday Kishore, Abigail Robb, Michael Katotomichelakis, Gabriële Holtappels, Lara Derycke, Francis Corazza, Rémy von Frenckell, Nathalie Wathelet, Jean Duchateau, Thierry Legon, Sabine Pirotton, Stephen R Durham, Claus Bachert, Mohamed H Shamji, Hanisah Sharif, Iesha Singh, Lubna Kouser, Ralph Mösges, Marie-Alix Bonny, Angeliki Karamani, Rebecca V Parkin, Nicolas Bovy, Uday Kishore, Abigail Robb, Michael Katotomichelakis, Gabriële Holtappels, Lara Derycke, Francis Corazza, Rémy von Frenckell, Nathalie Wathelet, Jean Duchateau, Thierry Legon, Sabine Pirotton, Stephen R Durham, Claus Bachert, Mohamed H Shamji
Abstract
Background: A 3-week short-course of adjuvant-free hydrolysates of Lolium perenne peptide (LPP) immunotherapy for rhinoconjunctivitis with or without asthma over 4 physician visits is safe, well tolerated, and effective.
Objective: We sought 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.govNCT02560948).
Methods: Participants were randomized to receive LPP (n = 21) or placebo (n = 11) for 3 weeks over 4 visits. Grass pollen-induced basophil, T-cell, and B-cell responses were evaluated before treatment (visit [V] 2), at the end of treatment (V6), and after the pollen season (V8).
Results: Combined symptom and rescue medication scores (CSMS) were lower during the peak pollen season (-35.1%, P = .03) and throughout the pollen season (-53.7%, P = .03) in the LPP-treated group compared with those in the placebo-treated group. Proportions of CD63+ and CD203cbrightCRTH2+ basophils were decreased following LPP treatment at V6 (10 ng/mL, P < .0001) and V8 (10 ng/mL, P < .001) compared to V2. No change in the placebo-treated group was observed. Blunting of seasonal increases in levels of grass pollen-specific IgE was observed in LPP-treated but not placebo-treated group. LPP immunotherapy, but not placebo, was associated with a reduction in proportions of IL-4+ TH2 (V6, P = .02), IL-4+ (V6, P = .003; V8, P = .004), and IL-21+ (V6, P = .003; V8, P = .002) follicular helper T cells. Induction of FoxP3+, follicular regulatory T, and IL-10+ regulatory B 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 immunologic mechanisms of LPP immunotherapy are underscored by immune modulation in the T- and B-cell compartments, which is necessary for its effect.
Keywords: Allergy; follicular helper T cells; peptide immunotherapy; regulatory B cells; regulatory T cells.
Copyright © 2019. Published by Elsevier Inc.
Source: PubMed