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

doi:10.1016/j.jaci.2019.02.023

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. DurhamClaus Bachert, Mohamed H. Shamji

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

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.gov NCT02560948). 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 CD203c^brightCRTH2⁺ 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⁺ T_H2 (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.

Original language	English
Pages (from-to)	738-749
Number of pages	12
Journal	Journal of Allergy and Clinical Immunology
Volume	144
Issue number	3
DOIs	https://doi.org/10.1016/j.jaci.2019.02.023
Publication status	Published - Sept 2019
Externally published	Yes

Keywords

Allergy
follicular helper T cells
peptide immunotherapy
regulatory B cells
regulatory T cells

ASJC Scopus subject areas

Immunology and Allergy
Immunology

Access to Document

10.1016/j.jaci.2019.02.023

Cite this

Sharif, H., Singh, I., Kouser, L., Mösges, R., Bonny, M. A., Karamani, A., Parkin, R. V., Bovy, N., Kishore, U., Robb, A., Katotomichelakis, M., Holtappels, G., Derycke, L., Corazza, F., von Frenckell, R., Wathelet, N., Duchateau, J., Legon, T., Pirotton, S., ... Shamji, M. H. (2019). Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial. Journal of Allergy and Clinical Immunology, 144(3), 738-749. https://doi.org/10.1016/j.jaci.2019.02.023

Sharif, H, Singh, I, Kouser, L, Mösges, R, Bonny, MA, Karamani, A, Parkin, RV, Bovy, N, Kishore, U, Robb, A, Katotomichelakis, M, Holtappels, G, Derycke, L, Corazza, F, von Frenckell, R, Wathelet, N, Duchateau, J, Legon, T, Pirotton, S, Durham, SR, Bachert, C & Shamji, MH 2019, 'Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy: A randomized, double-blind, placebo-controlled trial', Journal of Allergy and Clinical Immunology, vol. 144, no. 3, pp. 738-749. https://doi.org/10.1016/j.jaci.2019.02.023

@article{6f0f0d63e1e54e6d899614f27b96112b,

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

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.gov NCT02560948). 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",

author = "Hanisah Sharif and Iesha Singh and Lubna Kouser and Ralph M{\"o}sges and Bonny, \{Marie Alix\} and Angeliki Karamani and Parkin, \{Rebecca V.\} and Nicolas Bovy and Uday Kishore and Abigail Robb and Michael Katotomichelakis and Gabri{\"e}le Holtappels and Lara Derycke and Francis Corazza and \{von Frenckell\}, R{\'e}my and Nathalie Wathelet and Jean Duchateau and Thierry Legon and Sabine Pirotton and Durham, \{Stephen R.\} and Claus Bachert and Shamji, \{Mohamed H.\}",

note = "Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = sep,

doi = "10.1016/j.jaci.2019.02.023",

language = "English",

volume = "144",

pages = "738--749",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "3",

}

TY - JOUR

T1 - Immunologic mechanisms of a short-course of Lolium perenne peptide immunotherapy

T2 - A randomized, double-blind, placebo-controlled trial

AU - Sharif, Hanisah

AU - Singh, Iesha

AU - Kouser, Lubna

AU - Mösges, Ralph

AU - Bonny, Marie Alix

AU - Karamani, Angeliki

AU - Parkin, Rebecca V.

AU - Bovy, Nicolas

AU - Kishore, Uday

AU - Robb, Abigail

AU - Katotomichelakis, Michael

AU - Holtappels, Gabriële

AU - Derycke, Lara

AU - Corazza, Francis

AU - von Frenckell, Rémy

AU - Wathelet, Nathalie

AU - Duchateau, Jean

AU - Legon, Thierry

AU - Pirotton, Sabine

AU - Durham, Stephen R.

AU - Bachert, Claus

AU - Shamji, Mohamed H.

PY - 2019/9

Y1 - 2019/9

N2 - 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.gov NCT02560948). 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.

AB - 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.gov NCT02560948). 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.

KW - Allergy

KW - follicular helper T cells

KW - peptide immunotherapy

KW - regulatory B cells

KW - regulatory T cells

UR - http://www.scopus.com/inward/record.url?scp=85063746362&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85063746362&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2019.02.023

DO - 10.1016/j.jaci.2019.02.023

M3 - Article

C2 - 30844425

AN - SCOPUS:85063746362

SN - 0091-6749

VL - 144

SP - 738

EP - 749

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this