Allergen Specificity in Specific IgE Cutoff

Abstract

This cohort study examines the distribution of specific IgE levels to 5 common aeroallergens in 6-year-old Danish children.

The specific IgE (sIgE) cutoff of 0.35 kU_A/L used to confirm allergic sensitization originates from the detection limit of the first assays available. This has been shown to have limited clinical relevance and little concordance with the skin prick test,¹ which may be partially explained by the uniform use of this cutoff value for all tested allergens. There are substantial differences between the individual allergens as to molecular structure, affinity, and classes and newer assays have a lower detection limit of 0.1 kU_A/L.

Methods

In this cohort study, we investigated the distribution of sIgE levels to 5 common aeroallergens in 835 children age 6 years from the at-risk Copenhagen Prospective Study on Asthma in Childhood₂₀₀₀ (COPSAC₂₀₀₀) and the population-based COPSAC₂₀₁₀ mother-child cohorts.² We also investigated the distribution of sIgE levels among the children with symptoms of allergic rhinitis (AR) to the allergen in question.

The sIgE levels were assessed for Dermatophagoides pteronyssinus (HDM), cat, dog, grass, and birch using ImmunoCAP (Thermo Fisher Scientific) in 296 of the 411 children from COPSAC₂₀₀₀ (72%) and 539 of the 700 children from COPSAC₂₀₁₀ (77%). The diagnosis of AR was made by the COPSAC pediatricians through structured parental interviews requiring congruence between symptoms and relevant allergen exposure.

The Copenhagen Ethics Committee (HKF 01-289/96) and the Danish Data Protection Agency (2008-41-2434) approved the study. Oral and written informed consent was obtained from all parents. Prism 8 (GraphPad) was used to calculate values in the Figure and the interquartiles ranges (IQRs).

Figure. Distribution of Specific IgE (sIgE) Levels to 5 Common Aeroallergens.

Density plot showing the distribution of log₁₀-transformed values of sIgE for all children with levels within the detection limit (0.1 ≤ sIgE ≤ 100 kU_A/L) and for the children with allergic rhinitis (AR) to the same allergen. The median values are marked with an orange line, the quartiles with a blue line, and the commonly used cutoff values for sIgE to grade sensitization are marked with dashed lines. HDM indicates house dust mite.

Results

The log₁₀-transformed levels of sIgE against the 5 individual allergens for children with values within the detection limit of 0.1 to 100 kU_A/L and for children with AR to the same allergen are shown in a density plot in the Figure. The median values and the 25% and 75% values of sIgE levels are listed in the Table.

Table. Median Values of Specific IgE and the 25% and 75% Percentiles Among All Children With Measurable Levels and Among Children With AR to the Same Allergen.

Participants	HDM	HDM, AR	Cat	Cat, AR	Dog	Dog, AR	Grass	Grass, AR	Birch	Birch, AR
No.	207	10	133	12	158	10	191	28	133	18
Median (IQR), kUA/L	0.14 (0.04-1.51)	6.29 (0.67-16.4)	0.06 (0.02-0.31)	1.41 (0.22-26.5)	0.07 (0.03-0.30)	5.73 (0.54-28.1)	0.33 (0.04-1.60)	2.43 (0.72-20.0)	0.20 (0.04-1.72)	1.97 (0.12-37.9)

Abbreviations: AR, allergic rhinitis; HDM, house dust mite; IQR, interquartile range.

The median (IQR) value of sIgE in all children varied among the 5 allergens: HDM, 0.14 kU_A/L (0.04-1.51); cat, 0.06 kU_A/L (0.02-0.31); dog, 0.07 kU_A/L (0.03-0.30); grass, 0.33 kU_A/L (0.04-1.60); and birch, 0.20 kU_A/L (0.04-1.72). In the children with AR to the same allergen, the median (IQR) values of sIgE were higher and had great variation: HDM, 6.29 kU_A/L (0.67-16.4); cat, 1.41 kU_A/L (0.22-26.5); dog, 5.73 kU_A/L (0.54-28.1); grass, 2.43 kU_A/L (0.72-20.0); and birch, 1.97 kU_A/L (0.12-37.9). An overlap existed in levels between symptomatic and asymptomatic children, with many asymptomatic children demonstrating very high levels.

Discussion

These findings highlight the problem of using the same sIgE cutoff for all allergens. Our results align with previous studies that have attempted to define new sIgE sensitization thresholds for food allergens by using double-blinded placebo-controlled food challenges.³ They report a much higher cutoff value for predicting clinical reactivity than the current sensitization threshold of 0.35 kU_A/L and great variation in cutoffs between allergens. For aeroallergens, to our knowledge only few studies have tried to define the levels of sIgE separating symptomatic and asymptomatic individuals. One cross-sectional study of children and adults also showed results in agreement with ours; however, they grouped the aeroallergens in seasonal and perennial allergens, not showing results for the individual allergens.⁴

Furthermore, there is a potential importance of low levels of sIgE. A Swedish study of 268 children showed that sIgE levels between 0.1 to 0.7 kU_A/L to egg and/or cow’s milk early in life increased the risk of sensitization and eczema later in childhood.⁵ Additionally, newer studies of wasp venom allergy and drug allergies indicate the importance of low levels of sIgE in terms of clinical reactivity.⁶ Therefore, we cannot rule out that even low levels of sIgE may be of biological importance (eg, for predicting later symptomatic allergic disease).

Conclusions

We find that a uniform sIgE cutoff value across allergens does not exist. We advocate that updated cutoffs should be made to correctly predict clinically relevant sensitization.