Quantitative IgE analysis shows overall a clear match with the fluctuations of IgE findings over age already described in the literature. As in several other patient- and population-based studies, the quantitative IgE findings of this study show frequent sensitization to hen’s egg, cow’s milk, and peanut in the children studied [13]. Moreover, the results present young age and male gender as predictors of sensitizations [14].
Interestingly, with regard to the age of the sample population, we found an approximately bell-shaped distribution, which is interrupted, among other things, by a particularly high number of cases in 2–4-year-olds. Gellrich et al., who had performed a similar IgE serology study, had described a decline in the teenage years, which they had attributed to reduced participation in medical services [10]. Our sample had no such drop, which may be due to the fact that our highly specialized allergy centre is not a regular care facility but frequently visited by patients of all ages. This is corroborated by an average patient age of 43.5 years which closely reflects overall average age in Germany of 44.6 years [15]. Comparing patients whose serum was examined between 2003–2010 with those whose serum was examined between 2011 and 2020, our analysis shows a significant decrease in aeroallergen and increase in food sensitizations, with constant total IgE. This is interesting and may reflect a trend toward people seeking aid with possible food allergy which had previously not been that prominent in the media, whereas common allergic rhinoconjunctivitis is increasingly being treated by the general practitioner in Germany since reimbursement schemes have changed [16]. The finding still has to be confirmed by population-based data. It is noticeable that in the course of life there is a continuous decrease in total IgE, a phenomenon which is counted among the forms of immunosenescence [17, 18]. In 2005, Anja Mediaty and Karsten Neuber discovered a decrease in total and specific IgE in aging patients with asthma, allergic rhinitis and insect allergy but not in patients with atopic dermatitis [19].
As previously described in the literature, our data set also reflected epidemiological data with significantly higher rates of sensitization in the men than in the women [20,21,22]. Sun, Xiaxao, et al., examined a similarly sized sample of 15,534 Chinese patients for the presence of IgE sensitization. Gender comparison revealed significantly increased specific IgE positivities in the male group for almost all aero- and food allergens tested (including hen's egg, cow's milk, D. pteronyssinus, cat dander, dog dander, among others) with the exception of cowrie snail and mold mix compared to the female group. Although geographic and sociocultural differences undoubtedly influence allergens and allergen contact, both samples agree that males are more prone to sensitization than females [13]. That the male sex is more frequently affected by sensitization has been demonstrated in previous population-based studies [10, 23, 24]. While this discrepancy is unlikely to be explained by different allergen exposure, there are multiple hypotheses on the cause of male allergy preponderance ranging from different smoking habits [25] to differing dietary intakes of antioxidants [26].
Our results indicate significantly higher sensitizations in male sex to cow’s milk protein and chicken egg white, especially in infancy; a difference that dissipates around adolescence [23]. In a Swedish population-based birth cohort, Melén et al. followed over 4,000 subjects until 24 years of age. Their results also showed increased rates of cow's milk and chicken egg sensitization with a peak around 8 years of age, followed by a continuous decrease in specific IgE levels [27]. Again, male subjects were more frequently affected than females. As of now, only correlative relationships between allergy and sex could be established. The lack of comprehensive understanding of the root of this inter-sex discrepancy hampers the development of meaningful allergy prevention measures targeting males.
The earlier age peak for the above-mentioned food sensitizations in our German collective could be due to different diets or selection bias. According to this, young children in Germany could come into contact with hen's egg and cow's milk earlier or to higher amounts. Alternatively, patients may develop symptoms earlier than the general population. However, Skerven, et al. examined a Norwegian collective of infants in the first year of life. They were able to show that in this phase of life sensitization to chicken egg protein is particularly common, followed by cow's milk and peanut [14], which is in agreement with the results of our study as well as with those using American patient samples [28].
The Swedish researchers were able to demonstrate significantly higher rates of aeroallergen sensitization, esp. to timothy pollen, birch pollen, and cat epithelium, in the male subjects, which increased steadily until the final point of the study at 24 years of age. In fact, such a trend cannot be reconstructed from our data. In both sexes, the studied aeroallergens birch pollen, D. pteronyssinus, and cat epithelia show sensitization maximums earlier between 7 and 12 years of age with a subsequent slow gradual decrease in specific IgE levels over their lifetime. The present disparity might be due to a selection bias—in the Swedish birth collective, only new-born subjects were randomly selected, whereas our cross-sectional data are based on patients with predominantly specific allergological issues. Of course, lifestyle factors and differential allergen exposure could also play a role. As in the Swedish work, predominantly no gender-specific differences regarding possible food sensitization could be detected. Although some significant age-specific differences between the gender groups were found, it is difficult to determine their exact cause. Overall, however, it can be seen that the sensitizations investigated decrease over the lifetime irrespective of gender. In the case of food sensitizations, there is a pronounced decrease until young adulthood.
Using mono-centric Patient Data as done in this study has the limitation that samples are from patients whose serum was tested for the presence of IgE due to specific allergological problems or questions. Therefore, it has been unclear, if the results are applicable to the general population (selection bias). Furthermore, in many cases, allergen panels created specifically for the hospital were taken (e.g., aeroallergen or food allergen panel). This leads to the fact that only a small part of all possible sensitizations was measured in each patient. For rare allergens, sensitizations only in a small number of cases were determined. Interestingly, despite these limitations, our results correspond surprisingly well to data from birth cohorts and may offer new insights, which can be confirmed in population-based studies [9, 29].
On the other hand, mass quantitative IgE analysis has decisive advantages. First, population-based conclusions can be extracted from data about how sensitizations develop over long periods of time. In contrast to most studies, which mainly examine children for reasons of practicability, the present method makes it possible to easily examine a wide variety of age groups with a minute amount of effort involved.
In summary, the present data demonstrates that our patient-based data results are largely congruent with already existing population-based sensitization data and therefore appear to be a valid surrogate in allergy research. To fully exploit the potential of quantitative IgE analysis available for allergy research, further studies are needed. Among other things, it would be interesting to apply the same methodology to a dataset that includes diagnostics of an even broader spectrum of sensitization of each patient, e.g. as determined in Thermo Fisher's ISAC diagnostics [30]. Simultaneous acquisition of all technically detectable sensitizations would lead to both a higher hit rate and greater interindividual comparability. Pooling of data between centres and/or allergy laboratories would largely increase sample numbers and might even more closely reflect sensitizations present in the population. Large datasets collected in this way could subsequently be examined for possibly existing sensitization patterns and profiles using machine-learning, which could provide further exciting insights. In the future, those insights could be used to identify allergy clusters in the population. With concise data on age, sex and even regional distribution, allergy prevention measures could be precisely targeted for optimal effectiveness.
