Characteristics of venom allergy at initial evaluation: Is fire ant hypersensitivity similar to flying hymenoptera?

Abstract Background Atopic dermatitis (AD) is a common chronic relapsing skin disease.Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. Objective The goal of this study was to fine map TSLP and evaluate associations with the onset and persistence of AD. Methods TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium (LD) and the persistence of AD over as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. Results The minor variant frequency for rs1898671 was 23.5% (95% CI: 21.4, 25.8). This variant was not in LD with other TSLP variants in the longitudinal cohort (N=741). White children with AD were less likely to have rs1898671 variant (1.41 (1.20, 1.66)) than a genomAD control. Children with AD and the rs1898671 variant during follow-up were more likely to have a remission than children who were wildtype for rs1898671 (OR: 1.56; 95% CI: 1.26, 1.91). In the second cohort (N=585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was found to be greater in rs1898671 heterozygotes (OR 1.91 (1.34, 2.75)) than homozygotes (OR: 1.28 (0.61, 2.70)). Conclusion TSLP and specifically rs1898671 is important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.