Analysis of Specific IgG4 Antibody and sIgG4/sIgE Antibody Ratio as Marker of Immune Tolerance to IgE-Mediated Response in Allergic Children

Background: The diagnosis and treatment of allergic diseases remain challenging because the results of allergy testing do not always correlate with clinical manifestations. For instance, although a specific IgE (sIgE) test for a particular allergen may be positive, some patients remain asymptomatic due to the development of immune tolerance. Recently, specific IgG4 (sIgG4) has been suggested as a potential indicator of immune tolerance. However, data in children are limited. Therefore, this study aimed to evaluate the clinical usefulness of sIgG4 testing and its potential role in assessing immune tolerance in pediatric allergic disease by measuring sIgE and sIgG4 levels. Methods: A total of 415 children with suspected allergic diseases were enrolled. All subjects underwent sIgE and sIgG4 testing for casein, egg white, peanut, Dermatophagoides farinae (D. farinae), dog dander, and birch. sIgE positivity was defined as a level of 0.35 kU/L or higher for each allergen. Test results and clinical characteristics were reviewed, and the association between symptom occurrence during actual allergen exposure and sIgG4 level or sIgG4/sIgE ratio was analyzed. Results: Among the 415 children, 253 were male (61%) and 162 were female (39%), with a median age of 5.77 years (IQR, 2.67–9.15). For inhalant allergens, sIgG4 levels did not differ between symptomatic and asymptomatic patients; however, the sIgG4/sIgE ratio was significantly higher in asymptomatic patients (D. farinae: p < 0.001, dog dander: p < 0.001, birch: p = 0.003)). For food allergens, significant differences in sIgE, sIgG4, and sIgG4/sIgE ratio were observed for casein (sIgE: p < 0.001, sIgG4: p < 0.001, sIgG4/sIgE: p < 0.001) and egg white (sIgE: p < 0.001, sIgG4: p < 0.001, sIgG4/sIgE: p < 0.001), while no significant associations were found for peanut. Conclusions: The correlation between sIgG4 and clinical symptom occurrence varied depending on the allergen. Although sIgG4 alone appears to have limited clinical value for inhalant allergens, the sIgG4/sIgE ratio may serve as a useful indicator of immune tolerance. For casein and egg white, both sIgG4 and the sIgG4/sIgE ratio demonstrated potential clinical utility for identifying immune tolerance; however, further investigation is needed to validate the role of sIgG4-based indicators in pediatric allergy management.