Detection of casein-IgE interaction in cow’s milk allergic children through impedenzimetric measurements

Background: Cow's milk allergy (CMA) is one of the main food allergies in children. Currently, CMA is usually diagnosed based on clinical history and evidence of specific IgE (s-IgE) to cow’s milk (CM). The s-IgE can be documented by skin prick test (SPT) or measurement of s-IgE in the serum. These diagnostic tools are not able to predict the severity of allergic reaction when the patient ingests the allergen. Despite the improved accuracy conferred by s-IgE to individual allergens (i.e casein), compared with IgE to allergen extracts (i.e CM), a significant proportion of patients who are assessed for possible CMA require oral food challenge (OFC), which is currently the reference standard to diagnose CMA. The OFC is a procedure not free from the risk of having significant allergic reactions, even life-threatening, such as anaphylaxis. Objective: The aim of the present study is to provide an alternative and more efficient method for diagnosis of CMA by measuring the impedance values of a patient's serum sample before and after its contact with an allergen of interest, in this case CM-casein, through an impedance measurement device. Methods: we enrolled children with a personal history of reaction to CM as well as patients without history of CMA (control group) referred to Allergy Unit of the Meyer Children’s Hospital, Florence, Italy (from September 2019 to September 2020). Children underwent SPT to CM and CM casein and a blood sample were collected to determine serum s-IgE to CM and CM casein. Patients with positive SPT or detectable CM casein-IgE underwent to OFC with baked milk. The OFC clinical manifestations were classified as mild, moderate, or severe and consequently the CM allergic patients were classified in different severity degree, in particular highly allergic (HA), medium allergic (MA) and low allergic (LA) children. For the impedenzimetric measurement an impedance measurement device was used. Results: Overall, 33 patients were enrolled: 15 children with CMA and 18 not-CM allergic children. The measurements obtained by impedance measure device showed difference, in term of IgE binding kinetic, between CM allergic children and not-CM allergic children. Moreover, it was possible to detect impedance variation between CM allergic group that can discriminate the grade of severity of CMA. Conclusions: Therefore, this new proposed approach improves the performance of the current test for serum s-IgE concentration in terms of assay time and, furthermore, provides information about the IgE binding kinetics that is related to the severity of the allergic reactions. Our results, although promising, need to be confirmed by more experiments.