title: Staphylococcus aureus fibronectin-binding protein specifically binds IgE from patients with atopic dermatitis and requires antigen presentation for cellular immune responses.
abstract: BACKGROUND
  Staphylococcus aureus superinfections occur in more than 90% of patients with atopic dermatitis (AD) and aggravate skin inflammation. S aureus toxins lead to tissue damage and augment T-cell-mediated skin inflammation by a superantigen effect.
  
  
  OBJECTIVE
  To characterize IgE-reactive proteins from S aureus.
  
  
  METHODS
  A genomic S aureus library was screened with IgE from patients with AD for DNA clones coding for IgE-reactive antigens. One was identified as fibronectin-binding protein (FBP). Recombinant FBP was expressed in Escherichia coli, purified, and tested for specific IgE reactivity in patients with AD. Its allergenic activity was studied in basophil activation experiments and T-cell cultures. The in vivo allergenic activity was investigated by sensitizing mice.
  
  
  RESULTS
  Using IgE from patients with AD for screening of a genomic S aureus library, an IgE-reactive DNA clone was isolated that coded for FBP. Recombinant FBP was expressed in E coli and purified. It reacted specifically with IgE from patients with AD and exhibited allergenic activity in basophil degranulation assays. FBP showed specific T-cell reactivity requiring antigen presentation and induced the secretion of proinflammatory cytokines from PBMCs. Mice sensitized with FBP mounted FBP-specific IgE responses, showed FBP-specific basophil degranulation as well as FBP-specific T-cell proliferation, and mixed T(h)2/T(h)1 cytokine secretion.
  
  
  CONCLUSIONS
  Evidence is provided that specific humoral and cellular immune responses to S aureus antigens dependent on antigen presentation represent a novel mechanism for S aureus-induced skin inflammation in AD. Furthermore, FBP may be used for the development of novel diagnostic and therapeutic strategies for S aureus infections.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Kavita
authors.initials: K
authors.lastname: Reginald
authors.forename: Kerstin
authors.initials: K
authors.lastname: Westritschnig
authors.forename: Birgit
authors.initials: B
authors.lastname: Linhart
authors.forename: Margarete
authors.initials: M
authors.lastname: Focke-Tejkl
authors.forename: Beatrice
authors.initials: B
authors.lastname: Jahn-Schmid
authors.forename: Julia
authors.initials: J
authors.lastname: Eckl-Dorna
authors.forename: Annice
authors.initials: A
authors.lastname: Heratizadeh
authors.forename: Angelika
authors.initials: A
authors.lastname: Stöcklinger
authors.forename: Nadja
authors.initials: N
authors.lastname: Balic
authors.forename: Susanne
authors.initials: S
authors.lastname: Spitzauer
authors.forename: Verena
authors.initials: V
authors.lastname: Niederberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Werfel
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Natalija
authors.initials: N
authors.lastname: Novak
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Hirschl
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007223:Infant; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D055815:Young Adult
chemical_list: D018829:Adhesins, Bacterial; D011994:Recombinant Proteins; D018089:Superantigens; C078635:fibronectin-binding proteins, bacterial; D007073:Immunoglobulin E