title: Serological, genomic and structural analyses of the major mite allergen Der p 23.
abstract: BACKGROUND
  Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein.
  
  
  OBJECTIVE
  This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population and to determine the structure for functional characterization.
  
  
  METHODS
  IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7 and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analysed by X-ray crystallography and NMR.
  
  
  RESULTS
  Despite a high prevalence of Der p 23, (75% vs. 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n = 47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23.
  
  
  CONCLUSIONS
  Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens.
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Mueller
authors.affiliation: Integrative Bioinformatics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Randall
authors.affiliation: INDOOR Biotechnologies, Inc., Charlottesville, VA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Glesner
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Pedersen
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Perera
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Edwards
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: DeRose
authors.affiliation: INDOOR Biotechnologies, Inc., Charlottesville, VA, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Chapman
authors.affiliation: Genome Integrity and Structural Biology Laboratory, Research Triangle Park, NC, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: London
authors.affiliation: INDOOR Biotechnologies, Inc., Charlottesville, VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Pomés
mesh_terms: D000485:Allergens / Q000737:chemistry* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000097:blood / Q000737:chemistry* / Q000276:immunology*; D018360:Crystallography, X-Ray; D004797:Enzyme-Linked Immunosorbent Assay; D023281:Genomics; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D007073:Immunoglobulin E
keywords: Der p 23; RNA-seq; allergen; house dust mite