title: The mucosal immune response to laryngopharyngeal reflux.
abstract: BACKGROUND
  Laryngopharyngeal reflux (LPR) affects up to 20% of Western populations. Although individual morbidity is usually moderate, treatment costs are high and there are associations with other diseases, including laryngeal cancer. To date, there have been no studies of the mucosal immune response to this common inflammatory disease.
  
  
  OBJECTIVE
  To determine the mucosal immune response to LPR.
  
  
  METHODS
  We performed a prospective immunologic study of laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11, respectively), and of primary laryngeal epithelial cells in vitro.
  
  
  RESULTS
  Quantitative multiple-color immunofluorescence, using antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68, EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II), and classical and nonclassical MHC (I, II, beta(2)-microglobulin, CD1d). Univariate and multivariate analysis and colocalization measurements were applied. There was an increase in percentage area of mucosal CD8(+) cells in the epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were unchanged. Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01).
  
  
  CONCLUSIONS
  These data indicate a role for the CD1d-NKT cell axis in response to LPR in humans. This represents a useful target for novel diagnostics and treatments in this common condition.
authors.affiliation: Laryngeal Research Group, University of Bristol, Langford House, Bristol, UK.
authors.forename: Louisa E N
authors.initials: LE
authors.lastname: Rees
authors.forename: Laszlo
authors.initials: L
authors.lastname: Pazmany
authors.forename: Danuta
authors.initials: D
authors.lastname: Gutowska-Owsiak
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Inman
authors.forename: Anne
authors.initials: A
authors.lastname: Phillips
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Stokes
authors.forename: Nikki
authors.initials: N
authors.lastname: Johnston
authors.forename: Jamie A
authors.initials: JA
authors.lastname: Koufman
authors.forename: Gregory
authors.initials: G
authors.lastname: Postma
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.forename: Martin A
authors.initials: MA
authors.lastname: Birchall
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005764:Gastroesophageal Reflux / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007013:Hypopharynx / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018928:Immunity, Mucosal / Q000502:physiology; D007820:Laryngeal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D015703:Antigens, CD