title: MUC5B expression and location in surfactant protein C mutations in children.
abstract: BACKGROUND
  Mutations in Surfactant Protein C (SFTPC) can lead to fibrotic interstitial lung disease (ILD) with variable phenotypes, especially in children. The sources of phenotype variability are incompletely understood. A common MUC5B promoter variant rs35705950 is associated with adult Idiopathic Pulmonary Fibrosis (IPF). We examined whether MUC5B is similarly linked to ILD secondary to SFTPC mutations.
  
  
  METHODS
  MUC5B concentration in bronchoalveolar lavage fluid (BALF) was measured in six pediatric patients with SFTPC mutations and diseased controls. Immunohistochemical localization of MUC5B was studied in fixed lung tissues in patients with SFTPC mutations, ABCA3 mutations, and controls. Genotyping for the MUC5B promoter variant rs35705950 was attempted in all samples.
  
  
  RESULTS
  MUC5B glycoprotein was increased in BALF of patients with SFTPC mutations compared to diseased controls (P = 0.04). MUC5B was unexpectedly present in cells morphologically consistent with alveolar epithelial type II cells in patients with SFTPC mutations in the BRICHOS domain. Genotyping for the MUC5B promoter variant was successful in 18/27 patients, and there was no significant relationship between the MUC5B promoter variant and the BALF or MUC5B localization.
  
  
  CONCLUSIONS
  MUC5B may play a role in the development of fibrosis in patients with SFTPC mutations, especially in patients with BRICHOS mutations. Understanding the role of MUC5B in adult and pediatric lung diseases may lead to a better understanding of the etiology of fibrotic lung disease as well as development of novel therapies.
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors: Deborah R
authors: DR
authors: Liptzin
authors: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Alan M
authors: AM
authors: Watson
authors: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Elissa
authors: E
authors: Murphy
authors: Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado, Aurora, Colorado.
authors: Miranda E
authors: ME
authors: Kroehl
authors: Department of Pathology and Laboratory Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Megan K
authors: MK
authors: Dishop
authors: Department of Pathology and Laboratory Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Csaba
authors: C
authors: Galambos
authors: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Christopher M
authors: CM
authors: Evans
authors: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: Marvin I
authors: MI
authors: Schwarz
authors: Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
authors: Robin R
authors: RR
authors: Deterding
authors: Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado.
authors: David A
authors: DA
authors: Schwartz
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism*; D008297:Male; D055257:Mucin-5B / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010865:Pilot Projects; D011401:Promoter Regions, Genetic; D011650:Pulmonary Alveoli / Q000166:cytology; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics*
chemical_list: C524578:MUC5B protein, human; D055257:Mucin-5B; D037721:Pulmonary Surfactant-Associated Protein C
keywords: bronchoalveolar lavage; interstitial lung disease; mucins; pediatrics; pulmonary fibrosis; rare diseases; single nucleotide polymorphism; surfactant