LaKeya C Hardy1,2, Johanna M Smeekens3,4, Michael D Kulis3,4. 1. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, 116 Manning Dr., Mary Ellen Jones Building Rm 3310, Chapel Hill, NC, 27599, USA. lchardy@email.unc.edu. 2. UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. lchardy@email.unc.edu. 3. UNC Food Allergy Initiative, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. 4. Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Abstract
PURPOSE OF REVIEW: Investigational allergen immunotherapies (AITs) including oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) have proven to increase allergen thresholds required to elicit an allergic reaction in a majority of subjects. However, these studies lack consistent biomarkers to predict therapy outcomes. Here, we will review biomarkers that are currently being investigated for AIT. RECENT FINDINGS: The mechanisms underlying the therapeutic benefit of AIT involve various cell types, including mast cells, basophils, T cells, and B cells. Skin prick and basophil activation tests assess effector cell sensitivity to allergen and are decreased in subjects on AIT. Allergen-specific IgE increases initially and decreases with continued therapy, while allergen-specific IgG and IgA increase throughout therapy. Allergen-induced regulatory T cells (Tregs) increase throughout therapy and were found to be associated with sustained unresponsiveness after OIT. Subjects on OIT and SLIT have decreased Th2 cytokine production during therapy. Although trends have been reported, a common limitation of these biomarkers is that none are able to reproducibly predict prognosis during AIT. Further studies are needed to expand the currently available biomarker repertoire to provide personalized approaches to AIT.
PURPOSE OF REVIEW: Investigational allergen immunotherapies (AITs) including oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) have proven to increase allergen thresholds required to elicit an allergic reaction in a majority of subjects. However, these studies lack consistent biomarkers to predict therapy outcomes. Here, we will review biomarkers that are currently being investigated for AIT. RECENT FINDINGS: The mechanisms underlying the therapeutic benefit of AIT involve various cell types, including mast cells, basophils, T cells, and B cells. Skin prick and basophil activation tests assess effector cell sensitivity to allergen and are decreased in subjects on AIT. Allergen-specific IgE increases initially and decreases with continued therapy, while allergen-specific IgG and IgA increase throughout therapy. Allergen-induced regulatory T cells (Tregs) increase throughout therapy and were found to be associated with sustained unresponsiveness after OIT. Subjects on OIT and SLIT have decreased Th2 cytokine production during therapy. Although trends have been reported, a common limitation of these biomarkers is that none are able to reproducibly predict prognosis during AIT. Further studies are needed to expand the currently available biomarker repertoire to provide personalized approaches to AIT.
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