Mechanisms and predictive biomarkers of allergen immunotherapy in the clinic.

Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for IgE-mediated allergic diseases such as allergic rhinitis (AR). It can provide long-term clinical benefits when given for three years or longer. Mechanisms of immune tolerance induction by AIT are underscored by the modulation of several compartments within the immune system. These include repair of disruption in epithelial barrier integrity, modulation of the innate immune compartment that includes regulatory dendritic cells (DCreg) and innate lymphoid cells (ILCreg), and adaptive immune compartments such as induction of regulatory T and B cells. Altogether, these are also associated with dampening allergen-specific Th2 (Th2A) and T follicular helper cell responses and subsequent generation of blocking antibodies. Whilst AIT is effective in modifying the immune response, there is a lack of validated and clinically relevant biomarkers that can be used to monitor desensitization, efficacy, and the likelihood of response, all of which can contribute to accelerating personalized medication and increasing patient care. Candidate biomarkers comprise humoral, cellular, metabolic and in vivo biomarkers; however, these are primarily studied in small trials and require further validation. In this review, we evaluate the current candidates of biomarkers of AIT and how we can implement changes in future studies to help us identify clinically relevant biomarkers of safety, compliance and efficacy.