Nasal secretions trace epithelial type 2 response to allergen-specific immunotherapy

Background: Allergen-specific immunotherapy (AIT) is a disease-modifying therapy and is effective to reduce the symptoms of grass pollen-allergy. The airway epithelium of these patients releases inflammatory mediators including type-2 cytokines, which are associated with cellular processes involved in the symptomatic response of the affected tissue. Aim of the study was to identify epithelial biomarkers indicating AIT progress. Methods: In an exploratory, observational allergy cohort, we longitudinally phenotyped 56 grass pollen-allergic patients undergoing AIT for over three years and 18 controls using nasal secretions at critical time windows during therapy to assess peak-season responses along the course of therapy. Type-2 cytokine protein levels were analyzed using the high-sensitivity multiplex electrochemiluminescence mesoscale technique. Results: The type-2 cytokines CCL26 and POSTN oscillated seasonally, in contrast to TSLP and IL-33. However, only POSTN was reduced over the three-year AIT progression. In addition to POSTN, IL-24 and IL-37 levels were continuously reduced during AIT, while IFN-g and CCL27 were increased. Compared to healthy individuals, AIT did not restore healthy secretion levels but rather induced a novel homeostasis Conclusion: Nasal secretions trace the epithelial response during different phases of AIT. We demonstrate that AIT only partially controls the epithelial type 2 cytokine CCL26, which also adapts to seasonal changes, while POSTN and IL-24 are potential indicators of therapy success. Therefore, nasal secretions represent a promising, non-invasive tool for monitoring seasonal progress of AIT.