Natural tolerance development in cow's milk allergic children:IgE and IgG4 epitope binding

Abstract

Background

Although most of cow's milk (CM) allergic children will outgrow their allergy, the pathomechanism of the natural development of tolerance remains poorly understood. It has been suggested that the balance between milk specific IgE and IgG4 plays a major role.

Objective

We aimed to investigate differences in IgE and IgG₄ antibody binding to cow's milk (CM) epitopes between patients with persistent CM allergy (CMA) and those that naturally became tolerant.

Methods

Sera from thirty-five children with proven CMA (median age at inclusion of 10 months) were analysed retrospectively; 22 patients have become tolerant (median age at tolerance acquisition of 51 months) during the study period as confirmed by a negative oral food challenge. IgE and IgG4 binding to sequential epitopes derived from 5 major CM proteins were measured with a peptide microarray-based immunoassay.

Results

At baselines, greater intensity and broader diversity of IgE and IgG4 binding have been found in children with persistent CMA beyond 5 years of age compared to patients with transient CMA. Moreover, children with transient CMA had IgE and IgG4 antibodies that more often recognized the same epitopes, compared to those with persistent CMA. From baseline to the time of tolerance development, both IgE and IgG4 binding intensity decreased significantly, particularly in areas of α-s- and β-casein (p<0.01, FDR<0.1). Interestingly, differences between IgE and IgG4 binding intensity to CM peptides decreased when the patients became tolerant.

Conclusions

Our results suggest that the overlap between IgE and IgG4 might be important in natural tolerance acquisition. Further studies are needed to confirm our data and can eventually lead to development of more targeted treatment of food allergy.

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