Allergic diseases commonly coexist, manifesting in a sequence described as the "allergic march". Background/Objectives: This study aimed to evaluate TSLP's and IL-1β's potential as biomarkers in both single and multi-pediatric atopic diseases like atopic eczema, food allergy, and anaphylaxis and analyze specific SNPs in the TSLP and IL-1β genes to determine their associations with their occurrence and severity. Methods: This analysis included 109 atopic children diagnosed with atopic dermatitis, food allergy, or anaphylaxis alongside a control group of 57 non-atopic children. Recruitment was facilitated through the use of a comprehensive questionnaire. For the study population, the allergen profile was characterized at the molecular level by measuring specific IgE to purified natural or recombinant allergens, assessing serum levels of circulating TSLP and IL-1β, and identifying single-nucleotide polymorphisms in TSLP (rs2289277) and IL-1β (rs16944 C-511T). Results: The serum levels of TSLP and IL-1β were elevated in the study groups compared to the control group, highlighting their significance in the pathogenesis of the studied diseases. Carrying a higher number of the risk allele [C] in the TSLP SNP rs2289277 is associated with the greatest likelihood of having multiple concurrent allergic conditions, with the highest risk observed in individuals with all three conditions-atopic dermatitis, food allergy, and anaphylaxis, simultaneously. Moreover, children carrying the risk allele had a twofold increased risk of polysensitization, which rose to sixfold in those with two copies of the risk allele. Although no significant variations in genotype frequencies were detected for IL-1β rs16944, significant associations were observed for TSLP rs2289277, particularly with conditions such as atopic dermatitis, food allergy, anaphylaxis, and combinations of these diseases. Conclusions: Further research is required to elucidate these pathways and their role in the development of allergic diseases.
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