Early IL-10 producing B-cells and coinciding Th/Tr17 shifts during three year grass-pollen AIT

Ulrich M. Zissler, Constanze A. Jakwerth, Ferdinand M. Guerth, Lisa Pechtold, Juan Antonio Aguilar-Pimentel, Katharina Dietz, Kathrin Suttner, Guido Piontek, Bernhard Haller, Zuzana Hajdu, Matthias Schiemann, Carsten B. Schmidt-Weber, Adam M. Chaker

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Background: Allergen-specific immunotherapy (AIT) is a causative treatment in allergic airway disease, comprising long-term allergen administration and requiring three years of treatment. Mechanisms and biomarkers that translate into clinical efficacy remain urgently needed. Methods: In an exploratory observational allergy cohort we phenotyped 32 grass-pollen allergic patients with hayfever undergoing AIT for over three years and controls using local and systemic samples for ex vivo FACS, nasal transcriptomes and in vitro phleum-stimulation at critical time windows six hours after therapeutic allergen administration and during peak-season responses. Findings: The up-dosing phase is marked by increased IL-10 + B-cells with allergen-specific PD-L1 up-regulation, while effector Th1/Th17 cells and CCR6 + IL-17 + FoxP3 + T-cells decrease. The conversion phase exhibits Th17 recovery in the absence of Th2 cells. The tolerance-mounting phase after three years of treatment is characterized by induction of Tregs while Th2 and phleum-specific Th17 responses decrease. Notably, high ratios of circulating Breg/Th17 following initial AIT correlate significantly with clinical improvement after three years. Interpretation: Our exploratory data hypothezise differential shifts in the hierarchy of tolerance in three distinct phases of AIT characterized by conversion of regulatory against pro-inflammatory mechanisms, of which the Breg/Th17 ratio after initial treatment emerges as potential early prediction of AIT efficacy. Fund: This study was partially funded by Allergopharma GmbH & Co. KG, intramural funding and the German Center for Lung Research (DZL).

Original languageEnglish
Pages (from-to)475-488
Number of pages14
JournaleBioMedicine
Volume36
DOIs
StatePublished - Oct 2018

Keywords

  • Allergic Rhinitis
  • Allergy
  • Biomarker
  • Prediction
  • Regulatory B-cells (Bregs)
  • Regulatory T-cells (Tregs)
  • Specific Immunotherapy
  • Surrogate
  • Tolerance

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