Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial

J Allergy Clin Immunol. 2019 Sep;144(3):738-749. doi: 10.1016/j.jaci.2019.02.023. Epub 2019 Mar 5.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • Asthma / immunology
  • Asthma / therapy*
  • B-Lymphocytes, Regulatory / immunology
  • Conjunctivitis / immunology
  • Conjunctivitis / therapy*
  • Desensitization, Immunologic
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Lolium / immunology*
  • Male
  • Peptides / immunology
  • Peptides / therapeutic use*
  • Pollen / immunology*
  • Rhinitis, Allergic, Seasonal / immunology
  • Rhinitis, Allergic, Seasonal / therapy*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Young Adult

Substances

  • Allergens
  • Immunoglobulin G
  • Peptides
  • Immunoglobulin E

Associated data

  • ClinicalTrials.gov/NCT02560948