Identification of potential inflammation markers for outgrowth of cow’s milk allergy

Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) is an immune-mediated reaction to cow’s milk (CM). Non-IgE-mediated CMA resolves in most children in the first years of life, whereas IgE-mediated CMA outgrowth is often later or not at all. The exact mechanisms underlying resolution of IgE-mediated CMA are not fully understood. We aim to gain insight in the immunological mechanisms underlying resolution of IgE-mediated CMA by analyzing unique saliva samples of allergic infants using the Olink^® Target 96 Inflammation panel. Twenty-four children who outgrew their CMA after 12 months were compared to 15 with persistent CMA. Persistent CMA was accompanied by an increase in interleukin-15 receptor subunit alpha in the first 6 months, followed by a decrease, hinting towards an initial increased T cell response. At the same time caspase-8 was increased and interleukin-7 was decreased in persistent CMA. For CMA resolution, we found elevated levels of delta and notch-like epidermal growth factor-related receptor. Furthermore, adenosine deaminase (ADA) increased significantly between 0 and 12 months in resolved CMA, but not in persistent CMA. KEGG pathway analysis suggests mainly the TNF signaling pathway to be important in the resolution of CM allergy. Our findings show that Olink^® Target 96 Inflammation panel analysis of saliva samples can reveal potential immunological markers and mechanisms involved in CMA resolution.