Allergen-specific immunotherapy (AIT) is considered the only curative treatment for allergic diseases mediated by immunoglobulin E (IgE). Currently, the route of administration depends both on the different types of causal allergens and on its effectiveness and safety profile. Several studies have reported the mechanisms and changes in humoral and cellular response underlying AIT; however, the full picture remains unknown. Knowledge of who can benefit from this type of treatment is urgently needed due to the patient safety risks and costs of AIT. In vivo or in vitro biomarkers have become a strategy to predict clinical outcomes in precision medicine. There are currently no standardized biomarkers that allow determining successful responses to AIT, however, some studies have found differences between responders and nonresponders. In addition, different candidates have been postulated that may have the potential to become biomarkers. In this review, we aim to summarize the findings to date related to biomarkers in different IgE-mediated allergic diseases (respiratory, food, and venom allergy) with the potential to define who will benefit from AIT.

Background: Antigen‐specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9‐specific B cells in oral allergen‐specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT.Methods: Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank. Bos d 9‐specific B cells were isolated by flow cytometry and RNA‐sequencing was performed. Protein profile of Bos d 9‐specific B cells was analyzed by proximity extension assay.Results: Increased frequencies of circulating milk allergen Bos d 9‐specific B cells were observed after OIT and NT. Milk‐desensitized subjects showed the partial acquisition of phenotypic features of remission, suggesting that desensitization is an earlier stage of remission. Within these most significantly expressed genes, IL10RA and TGFB3 were highly expressed in desensitized OIT patients. In both the remission and desensitized groups, B cell activation‐, Breg cells‐, BCR‐signaling‐, and differentiation‐related genes were upregulated. In NT, pathways associated with innate immunity characteristics, development of marginal zone B cells, and a more established suppressor function of B cells prevail that may play a role in long‐term tolerance. The analyses of immunoglobulin heavy chain genes in specific B cells demonstrated that IgG2 in desensitization, IgG1, IgA1, IgA2, IgG4, and IgD in remission, and IgD in NT were predominating. Secreted proteins from allergen‐specific B cells revealed higher levels of regulatory cytokines, IL‐10, and TGF‐β after OIT and NT.Conclusion: Allergen‐specific B cells are essential elements in regulating food allergy towards remission in OIT‐received and naturally resolved individuals.