Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy

Genetic factors and mechanisms underlying food allergy are largely unknown. Due to heterogeneity of symptoms a reliable diagnosis is often difficult to make. Here, we report a genome-wide association study on food allergy diagnosed by oral food challenge in 497 cases and 2387 controls. We identify five loci at genome-wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the cytokine gene cluster at 5q31.1, the filaggrin gene, the C11orf30/LRRC32 locus, and the human leukocyte antigen (HLA) region. Stratifying the results for the causative food demonstrates that association of the HLA locus is peanut allergy-specific whereas the other four loci increase the risk for any food allergy. Variants in the SERPINB gene cluster are associated with SERPINB10 expression in leukocytes. Moreover, SERPINB genes are highly expressed in the esophagus. All identified loci are involved in immunological regulation or epithelial barrier function, emphasizing the role of both mechanisms in food allergy

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

An interdisciplinary approach to characterize peanut‐allergic patients—First data from the FOOD@ consortium

Background: Peanut allergy is a frequent cause of food allergy and potentially life-threatening. Within this interdisciplinary research approach, we aim to unravel the complex mechanisms of peanut allergy. As a first step were applied in an exploratory manner the analysis of peanut allergic versus non-allergic controls. Methods: Biosamples were studied regarding DNA methylation signatures, gut microbiome, adaptive and innate immune cell populations, soluble signaling molecules and allergen-reactive antibody specificities. We applied a scalable systems medicine computational workflow to the assembled data. Results: We identified combined cellular and soluble biomarker signatures that stratify donors into peanut-allergic and non-allergic with high specificity. DNA methylation profiling revealed various genes of interest and stool microbiota differences in bacteria abundances. Conclusion: By extending our findings to a larger set of patients (e.g., children vs. adults), we will establish predictors for food allergy and tolerance and translate these as for example, indicators for interventional studies

Virucidal or Not Virucidal? That Is the Question—Predictability of Ionic Liquid’s Virucidal Potential in Biological Test Systems

For three decades now, ionic liquids (ILs), organic salts comprising only ions, have emerged as a new class of pharmaceuticals. Although recognition of the antimicrobial effects of ILs is growing rapidly, there is almost nothing known about their possible virucidal activities. This probably reflects the paucity of understanding virus inactivation. In this study, we performed a systematic analysis to determine the effect of specific structural motifs of ILs on three different biological test systems (viruses, bacteria and enzymes). Overall, the effects of 27 different ILs on two non-enveloped and one enveloped virus (P100, MS2 and Phi6), two Gram negative and one Gram positive bacteria (E. coli, P. syringae and L. monocytogenes) and one enzyme (Taq DNA polymerase) were investigated. Results show that while some ILs were virucidal, no clear structure activity relationships (SARs) could be identified for the non-enveloped viruses P100 and MS2. However, for the first time, a correlation has been demonstrated between the effects of ILs on enveloped viruses, bacteria and enzyme inhibition. These identified SARs serve as a sound starting point for further studies

Follow-up of hen’s egg allergic children: investigation of factors that influence the reevaluation of tolerance development

Background: In order to determine tolerance development in hen’s egg (HE) allergic children, international guidelines recommend an oral food challenge after 6-24 months. This study aimed to assess whether parents follow this advice and factors that influence their decision. Methods: A follow-up of 158 challenge-proven HE allergic children was performed. Families who did not come to a rechallenge were contacted by phone and a standardized survey relating to the current allergy status was conducted. Logistic regression models were used to assess the effect of clinical and laboratory characteristics on the reevaluation of the allergy status. Results: 35% of the HE-allergic children conducted a rechallenge in a hospital, 27% continued avoiding HE without reevaluation and 11% performed a “home-testing” with HE. The odds ratio for patients to test for HE tolerance at home instead of in a hospital increased 7.94 times (CI:2.31-27.31) for every decrease in the severity score at the initial challenge, and 3.24 times (CI:1.26-8.33) for every decrease of the baseline specific IgE CAP-class. Tolerance of heated HE prior to reevaluation was most frequent in the home-tested (100%) and was more frequent in patients, who continued avoidance (68%) compared to those, who were rechallenged (44%). Conclusions: Our data suggest an association between reaction severity as well as specific IgE levels at initial food challenge and the choice of families whether and how to evaluate natural tolerance development in their HE-allergic child. Individualized management may be needed in order to achieve safe and effective medical care for these patients.</jats:p