Immune Profile After Oral Immunotherapy in Children With Persistent Cow's Milk Protein Allergy

Cow's milk protein allergy (CMPA) is the most common food allergy in childhood. Oral immunotherapy (OIT) has proven effective in achieving tolerance in children with persistent CMPA (pCMPA), although the underlying immunological mechanisms that allow for tolerance remain incompletely understood. We aimed to characterize the immune profile of pCMPA children following successful OIT and compare it to healthy controls (HC).

Thirty pCMPA children and 33 HC were recruited. T and B cell populations were assessed by flow cytometry, and specific immunoglobulins (sIgs) to milk allergens were measured by fluorometric enzyme-immunoassay.

Compared to HC, pCMPA children showed reduced B cells and activated T cells. Activated CD4⁺ T cells negatively correlated with OIT duration. Although sIgEs to casein remained ≥ class 3 in some patients, overall post-OIT sIgEs were lower compared to pre-OIT levels. Additionally, sIgG4 increased after OIT, particularly in patients with detectable sIgA. After OIT, pCMPA patients with sIgEs ≥ class 3 presented shorter relapse periods and fewer B cells and T cells compared to those with sIgEs < class 3. Interestingly, sIgEs correlated positively with regulatory T cells, though different sIgEs specificities showed distinct relationships with immune parameters. Age-related differences were observed: only children > 10 years showed significant reductions in T and B cells compared to their respective age-matched controls.

OIT modulates immune activation in pCMPA, reducing sIgE and increasing sIgG4 levels. Different relations between distinct sIgs and immune parameters may denote different stimulating and tolerance-inducing capacities for distinct cow's milk components. Age and time since OIT completion influence immune recovery, highlighting the complexity of tolerance mechanisms.