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.
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Karamani_Immunologic Mechanisms of Short-course of Lolium Perenne Peptide Immunotherapy_AAM.pdf - Accepted Version Download (6MB) | Preview |
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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