Short Course of Lolium Perenne Peptides (LPP) Immunotherapy Deletes Circulating IL-4+IL-21+ T follicular helper cells and Induces FoxP3+ T follicular regulatory cells: A Randomized Controlled Trial
Sunday, March 4, 2018: 4:30 PM
South Hall A2 (Convention Center)
Hanisah Sharif, BHSc MSc, Angeliki Karamani, Rebecca Parkin, Lubna Kouser, Iesha Singh, Abigail Robb, Gabriële Holtappels, Lara Derycke, Rémy von Frenckell, Nathalie Wathelet, Jean Duchateau, Thierry Legon, Sabine Pirotton, Ralph Mosges, MD FAAAAI, Stephen R. Durham, MD MA FRCP, Claus Bachert, MD PhD, Mohamed H. Shamji, BSc MSc PhD FAAAAI
RATIONALE: Allergen peptides are considered a safer alternative for immunotherapy due to their reduced capacity to bind to IgE and elicit anaphylaxis. IgE production by B cells requires signals from T follicular helper (Tfh) cells. This cellular interaction is tightly controlled by T follicular regulatory (Tfr) cells. We hypothesized that 3-weeks treatment with subcutaneous peptide hydrolysates from Lolium Perenne (LPP) is effective and supresses pro-allergic IL-4+, IL-21+ and dual IL-4+IL-21+ Tfh cells whilst at the same time inducing ‘protective’ Tfr cells.

METHODS: In a randomized controlled trial, participants received LPP(n=22) or placebo(n=11) for 3 weeks. Circulating allergen-driven CD4+CXCR5+PD-1+Tfh, IL-4+/IL-21+Tfh, FoxP3+Tfr, FoxP3+Treg cells and sIgE levels were enumerated before (V2), and after treatment (V6) and at the end of the pollen season (V8).

RESULTS: Peak-seasonal symptom scores were lower in LPP compared to placebo-treated group(P<0.05). Circulating pro-allergic IL-4+Tfh, IL-21+Tfh and dual-positive IL-4+IL-21+Tfh cells as well as IL-4+Th2 cells were decreased in LPP compared to placebo-treated group at V6(all,P<0.01). This reduction persisted at V8(P<0.05). Conversely, circulating FoxP3+Tfr and suppressive CTLA4+Tfr cells were increased in the LPP group at V6(all,P<0.01) and remained elevated at V8(P<0.01). In addition, FoxP3+Treg cells were increased in LPP-treated group at V6(P<0.05). Suppressive and functional GARP+ and SATB1-Treg cells were also induced in LPP-treated group at V6(P<0.05) and at V8(P<0.05). No changes were observed in placebo-treated participants.

CONCLUSIONS: For the first time, we showed that a short-course of LPP immunotherapy suppressed pro-allergic IL-4+ and IL-21+Tfh cells and induced Tfr and Treg cells in peripheral blood in association with the observed clinical benefit.