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Published on: April 21, 2019
Cut-off values for total serum immunoglobulin E between non-atopic and atopic children in north-west Croatia
Slavica Dodig1, Darko Richter, Bojan Benko
1National Reference Center for Pediatric Allergy, Pediatric Hospital Srebrnjak, Srebrnjak 100, 10000 Zagreb, Croatia. slavica.dodig@zg.t-com.hr
Insights
This study establishes reference values for total serum immunoglobulin E (IgE) in children, crucial for diagnosing atopy and respiratory conditions. Findings provide age-specific cut-offs to differentiate between atopic and non-atopic children.
Area of Science:
- Pediatric Allergy and Immunology
- Clinical Diagnostics
- Respiratory Medicine
Background:
- Distinguishing between atopic and non-atopic children with respiratory symptoms is clinically significant.
- Total serum immunoglobulin E (IgE) levels are a key biomarker in allergy diagnosis.
- Establishing age-appropriate reference ranges for total IgE is essential for accurate interpretation in pediatric populations.
Purpose of the Study:
- To determine reliable cut-off values for total serum immunoglobulin E (IgE) differentiating non-atopic from atopic children.
- To evaluate the utility of percentiles and receiver operating characteristic (ROC) analysis for establishing these cut-off values.
- To provide age-specific reference ranges for total IgE in children aged 0-16 years with respiratory symptoms.
Main Methods:
- A cohort of 7715 children (0-16 years) with respiratory symptoms was divided into non-atopic (n=3355) and atopic (n=4620) groups based on allergen-specific IgE levels.
- Total serum IgE levels were measured and analyzed for age-related trends and distribution characteristics (mean, median, skewness).
- Cut-off values were calculated using receiver operating characteristic (ROC) analysis, comparing upper percentiles of non-atopic children with lower percentiles of atopic children.
Main Results:
- Serum total IgE levels increased with age in both groups, plateauing around 9-10 years.
- Atopic children exhibited significantly higher total IgE levels (average 14-fold) compared to non-atopic children.
- The 95th percentile for non-atopic children and the 10th percentile for atopic children served as cut-offs up to age 8; ROC analysis yielded high diagnostic accuracy (96% sensitivity, 91% specificity, 0.950 AUC).
Conclusions:
- The 95th percentile of total IgE in non-atopic children and the 10th percentile in atopic children are useful cut-offs up to age 8.
- Significant percentile discrepancies emerge after age 8, necessitating age-specific interpretation.
- ROC analysis provides the most robust method for determining total IgE cut-off values due to irregular centile distributions in atopic subjects.
Background:
The aim of this study was to determine cut-off values for total serum immunoglobulin E (IgE) between non-atopic and atopic children with respiratory symptoms. Children of 0-16 years of age were evaluated for respiratory symptoms of >4-week duration.
Methods:
Children were divided into two groups: non-atopic children (n=3355) who were non-IgE-sensitized with undetectable allergen-specific IgE (<0.35 kIU(A)/L), and atopic children (n=4620) who were sensitized to > or =1 allergens (specific IgE > or =0.35 kIU(A)/L). Upper and lower centiles were determined and cut-off values calculated using receiver operating characteristic (ROC) analysis.
Results:
Serum total IgE increased with age in both groups, although at a variable level and rate, and reached a plateau at 9 and 10 years in non-atopic and atopic children, respectively. Atopic children had on average 14-fold higher serum total IgE compared to non-atopic children. In both groups, the median was lower than the corresponding mean and the distribution skewness was always positive (group I, 0.87; group II, 0.91). In almost all age groups, the 95th percentile for non-atopic children corresponded to the calculated cut-off values, whereas the 10th percentile for atopic children corresponded to the respective cut-off values only until the age of 8 years, after which greater differences between the cut-off values and the 10th percentile were recorded. Cut-off values for total serum IgE in children up to 16 years were determined with diagnostic sensitivity, specificity and area under the ROC curve of 96%, 91% and 0.950, respectively.
Conclusions:
The 95th percentile for total IgE in non-atopic children and the 10th percentile in atopic children could be taken as cut-off values in children up to 8 years of age, after which significant percentile discrepancies between non-atopic and atopic children were recorded. Since atopic subjects show a more irregular centile distribution, cut-off values are best determined by ROC analysis.

