Updates on Immunologic Responses to Aeroallergen Immunotherapy Since the 2011 US Practice Parameters on Allergen Immunotherapy.

PURPOSE OF REVIEW: In 2011, the AAAAI/ACAAI Joint Task Force published the third practice parameter on allergen immunotherapy (AIT), summarizing the contemporary understanding of AIT immunologic mechanisms. Since, major advances have substantially expanded insight into this complex field. This review briefly revisits earlier concepts and then focuses on newer mechanistic findings and emerging ideas, that yet have to be developed further to better understand AIT mechanisms. RECENT FINDINGS: Structural cells are now recognized as active contributors to the initiation of allergic inflammation; AIT reduces their pro-inflammatory activation. The innate immune system particularly type 2 innate lymphoid cells (ILC2s), plays an important role in initiating and sustaining allergic responses. AIT reduces the activation and/or number of the innate immune cells, potentially contributing to immune tolerance. Within the adaptive immune system Th2A and Tfh13 are the main pro-allergic effector cells, while regulatory T and B-cell subsets have been identified as key mediators of the long-term tolerance induced by AIT. Mechanistic differences between sublingual and subcutaneous AIT are also increasingly apparent: SCIT promotes serum allergen-specific IgG4 and serum blocking activity, while SLIT induces local nasal allergen-specific IgA1. Finally, AIT dose-response relationships vary between individuals, which may explain the clinical need for dose adjustments in some patients. The significance of molecular, proteomic, genetic and metabolic changes documented with AIT remains under investigation. Advances in understanding allergic immune responses and the complex immune changes (including cell plasticity) induced by AIT, might pave the way for enhanced AIT efficacy and predictive biomarkers in the future.