Surrogate Markers for Allergen-Specific Immunotherapy

Abstract

Allergen-specific Immunotherapy (AIT) still remains the only option for the long-term management of allergic rhinitis and allergic asthma, including disease due to house dust mite (HDM) allergy. In vivo provocation tests (e.g., skin testing and conjunctival provocation testing) are useful indicators of clinical improvement, but the identification of in vitro markers for monitoring the effects of AIT has been a long-sought goal. Previous studies on AIT in IgE-mediated allergic diseases found that suppression of allergen-induced late skin responses occurred as early as 2–4 weeks and was accompanied by increases in IL-10, whereas suppression of the immediate skin response to allergen occurred later, at 6–12 weeks, and was accompanied by increases in serum ‘blocking’ IgG4 antibodies that had the capacity to suppress both allergen-triggered basophil histamine release and the binding of IgE-allergen complexes to B cells. It has been claimed that a flow cytometry-based assay (IgE-FAB) can be used to demonstrate IgE-facilitated antigen presentation and activation of T cells. Measurement of peripheral T cell responses is complex and difficult to standardize for routine clinical use. Whether quantitative measures of IgG-associated inhibition (in contrast to IgG levels) and/or suppression of early and/or late skin responses may predict AIT efficacy and long-term benefits in individual patients remains to be determined. The search for adequate biological markers that reflect the immune status of patients before, during, and after AIT is critical to evaluate its clinical efficacy and the future of personalized medicine in treating allergic diseases.