title: Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis.
abstract: Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations.
  
  
  
  Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity.
  
  
  
  For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer ≥1:160, suggesting potential diagnostic capability of this assay.
  
  
  
  The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin.
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology, and Pulmonary Medicine, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Chadha
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Isaac P
authors.initials: IP
authors.lastname: Thomsen
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jimenez-Truque
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Soper
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Division of Allergy, Immunology, and Pulmonary Medicine, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Sokolow
authors.affiliation: Department of Microbiology, New York University School of Medicine, New York, NY.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Torres
authors.affiliation: Department of Pediatrics, Division of Infectious Diseases, The Monroe Carell, Jr. Children's Hospital at Vanderbilt and the Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: C Buddy
authors.initials: CB
authors.lastname: Creech
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000917:Antibody Formation / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology / Q000628:therapy; D003603:Cytotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007956:Leukocidins / Q000276:immunology*; D008171:Lung Diseases / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D008297:Male; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000276:immunology / Q000302:isolation & purification; D000067251:Symptom Flare Up; D014481:United States
chemical_list: D001426:Bacterial Proteins; D003603:Cytotoxins; D007956:Leukocidins; C586430:leukocidin AB, Staphylococcus aureus
keywords: Cystic fibrosis; Exotoxins; LukAB; Serology; Staphylococcus aureus
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