A subclass IgG4-specific antigen-binding radioimmunoassay (RIA): Comparison between IgG and IgG4 antibodies to food and inhaled antigens in adult atopic dermatitis after desensitization treatment and during development of antibody responses in children

Abstract

A liquid-phase, antigen-binding radioimmunoassay measuring subclass IgG4 antibody (ab) to allergens has been developed. This assay, which uses monoclonal anti-IgG4 to bind IgG4, allows direct comparison of class (IgG)- and subclass (IgG4)-specific ab levels. These assays used radiolabeled purified allergens, Der p I (Ag P 1) from the dust mite Dermatophagoides pteronyssinus, Lol p I (Rye 1), from ryegrass pollen, hen's egg ovalbumin, and β-lactoglobulin from cow's milk. We have investigated IgG4 abs in several clinical situations. The results confirm that IgG ab responses to both inhalants and food proteins unequivocally include IgG4 ab. On average, the proportion of IgG4 ab to these antigens is far higher than the contribution of IgG4 to total IgG. In patients with adult atopic dermatitis, levels of both class and subclass ab were higher than in control subjects; however, the ratio of IgG4:IgG varied widely in patients and control subjects. During desensitization treatment of patients with perennial rhinitis, levels of IgG4 ab to Der p I increased sharply, but there were also increases in the total IgG ab responses so that the precentage contribution of IgG4 was only moderately increased (mean values: before, 29%; after, 36%). In a prospective study of children from atopic families, IgG4 abs to food proteins were detectable as early as 3 months. IgG abs to hen's egg ovalbumin and β-lactoglobulin from cow's milk increased to a maximum at 3 years and declined by 5 years. However, specific IgG4 as a percentage of specific IgG increased progressively from a mean value of ∼15% at 6 months to ∼50% at 5 years of age. Overall, the results do not support a role for IgG4 in immediate skin reactivity as the sole blocking ab or in the production of allergic symptoms. However, given the known properties of the IgG4 subclass, changes in IgG4 abs to food allergens could well alter the impact of these proteins on young children.