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. 2017 Mar 10;4(1):43–53. doi: 10.1007/s40521-017-0117-5

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© The Author(s) 2017

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Fig. 2 — Biomarkers associated with allergen response and AIT. Biomarkers for various cell types may exhibit clinical benefit for allergen immunotherapy. The conventional T cell response to allergen mediating a CD4⁺ T cell response has been widely evaluated. The increase of CD4⁺ T cells in response to allergen elicits a Th2 cytokine storm such as IL-4, IL-5, and IL-13 causing an allergic response or asthma. On the other hand, Tregs have a protective role in allergy as they modulate immune tolerance to allergen and control the allergic reaction during allergen immunotherapy. AIT deviates the immune response towards Tregs increasing the IL-10 and TGF-ß production with a decrease in IgE, whereas the elevated IgG4 as well as IgA is mediated by B cells. The increase in Treg subsets Foxp3⁺ and Tr1 are also induced by AIT may be important biomarkers post-immunotherapy. The immune response can become resistant to immune deviation to Tregs/Th1 subsets; CD4⁺T cells (CD27-) expressing CRTH2 also produce a Th2 response. The CD27^- (Th2) subset have been found to be decreased in AIT treated subjects, whereas the protective CD27⁺ (Th2) subset was elevated. Additionally, IL10+ Bregs can induce protective IgG4 response and inhibit the antigen-specific CD4⁺ T cell proliferation during AIT. Furthermore, the DC markers in response to immunotherapy have an increased DCreg (C1QA and FcεRIIIA) and decreased DC2 (GATA-3, CD141, and RIPK4) response. A novel biomarker for basophils has also been established intracellular expression of fluorochrome-labeled diamine oxidase, which was increased in SAR patients but reduced during SCIT and SLIT. The reduction in histamine, CD63, and CD203c by basophils was also associated with reduced symptoms.