The complexity of allergic patients' IgE repertoire correlates with serum concentration of allergen-specific IgE

Abstract

The governing factor of both effector-cell activation and facilitated antigen presentation is IgE-repertoire complexity (IgE-clonality, -affinity and -concentration). Yet, the compositions of individual IgE repertoires and correlation between IgE-repertoire complexity and establishment of allergic sensitization remain to be determined. In complex formation assays with recombinant IgE, allergen and CD23(+) B cells, we assess the composition of serum IgE repertoires and examine the correlation between IgE-titre and IgE-repertoire complexity. The capacity of sera, from house dust mite-sensitized individuals, to mediate IgE-Der p 2-CD23 complex formation on CD23(+) B cells was measured. In parallel experiments, the effect of supplementing each serum with one or more Der p 2-specific monoclonal recombinant IgE antibodies on complex formation was determined. Only sera with the highest concentration of Der p 2-specific IgE resulted in complex formation without supplementary recombinant IgE. Intermediately titred sera supported complex formation to various degrees when supplemented with individual recombinant IgE. The degree of complex formation depended on the affinity and epitope specificity of the recombinant IgE. Complex formation by combining serum and recombinant IgEs could not be obtained with sera of relatively low titres of specific IgE. However, these sera had the capacity to dramatically enhance the low complex formation achieved with pairs of affinity-engineered recombinant IgEs. Serum IgE complexity can be indirectly assessed by combining sera with defined monoclonal IgEs in IgE-allergen-CD23 complex assays. The observed differences in epitope-coverage of Der p 2-specific serum-IgE in sera of different specific IgE titres indicate that increased IgE titres correlate with increased complexity of the IgE-repertoire. A detailed knowledge of the composition and complexity of allergen-specific IgE repertoires (and the relation to IgE titre), particularly in the early phase of sensitization, may be used to improve the prediction of the persistence and severity of allergic symptoms, as well as the progression of the Allergic March.