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

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.

Taxanes in Taxus baccata pollen: cardiotoxicity and/or allergenicity?

Diterpenic alkaloids belonging to taxine (yield: 0.18 % dry weight) and taxoids (paclitaxel, baccatine III and 10-deacetylbaccatine III, cumulated yield: 0.004 % dry weight) were isolated from Taxus baccata L. pollen. Moreover, taxoids conjugated to macromolecules were also detected by ELISA. According to these data and to semi-quantitative measurements of pollen production, a hundred-year-old yew during its flowering time releases several grams of taxanes contained in 16 to 20 kg of pollen. Toxicity assays on mice indicated that any risk of acute toxicity resulting from Taxus pollen inhalation and subsequent taxine absorption is unlikely. On the other hand, anti-paclitaxel IgG were above all detected in sera of subjects displaying hypersensitivity reactions during the pollination periods of Taxus sp. and Betula sp. This natural anti-paclitaxel IgG acquisition by individuals living in the distribution areas of these trees could be at the origin of atopic manifestations. We also postulate that such a natural sensitization could have a marked influence on the tolerance to anticancer taxoids.