title: Unlike in Children with Allergic Asthma, IgE Transcripts from Preschool Children with Atopic Dermatitis Display Signs of Superantigen-Driven Activation.
abstract: The IgE repertoire in children with asthma reflects an adaptive B cell response, indicative of Ag-driven selection. However, the same might not apply to atopic dermatitis, which is often the first manifestation of atopy. The objective of our present study was to characterize the IgE repertoire of preschool children with atopic dermatitis with regard to signs of superantigen-like activation, clonal relationship, and indications of Ag selection. Total RNA was isolated from PBMCs of five children with atopic dermatitis. IgE transcripts were amplified, cloned, and sequenced using RT-PCR. We obtained 200 functional IgE sequences, which were compared with 1140 sequences from 11 children with asthma. Whereas variable gene segment of the H Ig chain (VH) gene usage in asthma reflected germline distribution, IgE transcripts from children with atopic dermatitis displayed a dominance of the otherwise scarcely expressed VH2 and VH4 family. Whereas IgE transcripts from children with asthma were highly mutated (7.2%), somatic mutation rate in atopic dermatitis was less than half as high (3.4%). Moreover, the proportion of transcripts that were indicative of Ag selection was reduced to 11% in atopic dermatitis (24% in asthma). In summary, IgE repertoires vary significantly between children with different atopic diseases. Compared with children with asthma, IgE transcripts from preschool children with atopic dermatitis are significantly less mutated, clonally less focused, and less indicative of Ag selection. We consider our data reconcilable with the hypothesis that a superantigen-like activation contributes to the maturation and selection of the IgE repertoire in atopic dermatitis.
authors.affiliation: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg, St. Hedwig Campus, D-93049 Regensburg, Germany; and Department of Pediatrics, Philipps-University Marburg, D-35043 Marburg, Germany sebastian.kerzel@ukr.de.
authors.forename: Sebastian
authors.identifier: 0000-0003-1495-7279
authors.initials: S
authors.lastname: Kerzel
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, D-35043 Marburg, Germany.
authors.forename: Tobias
authors.identifier: 0000-0002-1674-1423
authors.initials: T
authors.lastname: Rogosch
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, D-35043 Marburg, Germany.
authors.forename: Benjamin
authors.identifier: 0000-0002-4205-9890
authors.initials: B
authors.lastname: Struecker
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, D-35043 Marburg, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Maier
authors.affiliation: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg, St. Hedwig Campus, D-93049 Regensburg, Germany; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.affiliation: Department of Pediatrics, Philipps-University Marburg, D-35043 Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zemlin
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000276:immunology*; D004485:Eczema / Q000235:genetics / Q000276:immunology; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007073:Immunoglobulin E / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007223:Infant; D008297:Male; D059645:Mutation Rate; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018089:Superantigens / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D018089:Superantigens; D007073:Immunoglobulin E