Search

Rationale: Approximately 32 million people in the United States suffer from food allergies. Some food groups, such as legumes – peanuts, tree nuts, fish, and shellfish, have a high risk of cross-reactivity. However, the murine model of multiple food group cross-reactivity is limited. Objective: We sought to develop a murine model that can be used to investigate novel therapeutics for the treatment of multiple food allergies. Methods: C3H/HeJ mice were sensitized intraperitoneally (i.p.) once a week for three weeks with a mixture of 500µg of protein from peanut, cashew, walnut, shrimp, cod, and 2 mg Alum. The control group consisted of naïve mice. IgE levels against the sensitized allergens and their cross-reactive allergens were measured by ELISA at baseline and 3 weeks after sensitization. In weeks 4 and 5, the mice were given intragastric challenges with 200mg/mouse of each food: peanut, chickpea, lentil, cashew, almond, pistachio, hazelnut, brazil nut, walnut, pecan, shrimp, lobster, cod, salmon, and mackerel. After each challenge, anaphylactic symptoms, rectal temperatures, and plasma histamine were measured. Results: There was a significant elevation of IgE against sensitized antigens (peanut cashew, walnut, shrimp, and cod) as well as cross-reactive allergens used for oral food challenge from legumes including peanut, chickpea, and lentil, as well as tree nuts such as cashew, almond, pistachio, hazelnut, brazil nut, walnut, and pecan. Furthermore, there was a significant increase in crustaceans such as shrimp, lobster and fish like cod, salmon, and mackerel (p <0.01). Consistently, significantly increased anaphylactic symptom scores (p <0.05), decreased rectal temperature (p <0.001), and increased plasma histamine (p <0.05) compared to the naïve mice occurred following each challenge with sensitized foods and unsensitized, but cross-reactive foods. Conclusion: We generated a comprehensive murine model of IgE-mediated multiple food groups of cross-reactive anaphylaxes. This will provide an essential tool for developing novel therapies for cross-reactivity multiple food allergies. [ABSTRACT FROM AUTHOR]

Deafness is the most frequent sensory disorder. With over 90 genes and 110 loci causally implicated in non-syndromic hearing loss, it is phenotypically and genetically heterogeneous. Here, we investigate the genetic etiology of deafness in four families of Iranian origin segregating autosomal recessive non-syndromic hearing loss (ARNSHL). We used a combination of linkage analysis, homozygosity mapping, and a targeted genomic enrichment platform to simultaneously screen 90 known deafnesscausing genes for pathogenic variants. Variant segregation was confirmed by Sanger sequencing. Linkage analysis and homozygosity mapping showed segregation with the DFNB57 locus on chromosome 10 in two families. Targeted genomic enrichment with massively parallel sequencing identified causal variants in PDZD7: a homozygous missense variant (p.Gly103Arg) in one family and compound heterozygosity for missense (p. Met285Arg) and nonsense (p.Tyr500Ter) variants in the second family. Screening of two additional families identified two more variants: (p.Gly228Arg) and (p.Gln526Ter). Variant segregation with the hearing loss phenotype was confirmed in all families by Sanger sequencing. The missense variants are predicted to be deleterious, and the two nonsense mutations produce null alleles. This report is the first to show that mutations in PDZD7 cause ARNSHL, a finding that offers addition insight into the USH2 interactome. We also describe a novel likely disease-causing mutation in CIB2 and illustrate the complexity associated with gene identification in diseases that exhibit large genetic and phenotypic heterogeneity. [ABSTRACT FROM AUTHOR]