title: Surfactant proteins in pediatric interstitial lung disease.
abstract: BACKGROUND
  Children's interstitial lung diseases (chILD) comprise a broad spectrum of diseases. Besides the genetically defined surfactant dysfunction disorders, most entities pathologically involve the alveolar surfactant region, possibly affecting the surfactant proteins SP-B and SP-C. Therefore, our objective was to determine the value of quantitation of SP-B and SP-C levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of chILD.
  
  
  METHODS
  Levels of SP-B and SP-C in BALF from 302 children with chILD and in controls were quantified using western blotting. In a subset, single-nucleotide polymorphisms (SNPs) in the SFTPC promoter were genotyped by direct sequencing.
  
  
  RESULTS
  While a lack of dimeric SP-B was found only in the sole subject with hereditary SP-B deficiency, low or absent SP-C was observed not only in surfactant dysfunction disorders but also in patients with other diffuse parenchymal lung diseases pathogenetically related to the alveolar surfactant region. Genetic analysis of the SFTPC promoter showed association of a single SNP with SP-C level.
  
  
  CONCLUSIONS
  SP-B levels may be used for screening for SP-B deficiency, while low SP-C levels may point out diseases caused by mutations in TTF1, SFTPC, ABCA3, and likely in other genes involved in surfactant metabolism that remain to be identified. We conclude that measurement of levels of SP-B and SP-C was useful for the differential diagnosis of chILD, and for the precise molecular diagnosis, sequencing of the genes is necessary.
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Lorenz
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Meike
authors.initials: M
authors.lastname: Hengst
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schams
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Traudl
authors.initials: T
authors.lastname: Wesselak
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rauch
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wittmann
authors.affiliation: Pediatric Pneumology, Charite, Berlin, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Kirchberger
authors.affiliation: Hospital Clinico Universitario, Unidad Neumologia Infantil, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Escribano
authors.affiliation: Neonatology, University Children's Hospital, Mannheim, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schaible
authors.affiliation: Pediatric Cardiology, University Children's Hospital, Tuebingen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Baden
authors.affiliation: Children´s Hospital, Johann Wolfgang Goethe-University, Frankfurt, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schulze
authors.affiliation: Pediatric Endocrinology, Charite, Berlin, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Aslanidis
authors.affiliation: Pediatric Pulmonology, Hannover Medical School, Hannover, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Schwerk
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.affiliation: Children's Hospital and Interdisciplinary Center for Infectious Diseases, University of Tuebingen, Tuebingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Praxis für Humangenetik, CeGaT GmbH, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
authors.affiliation: Dr von Hauner Children´s Hospital, German Center for Lung Research (DZL), University of Munich, Munich, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Zarbock
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D001991:Bronchitis / Q000235:genetics; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D004268:DNA-Binding Proteins / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D007223:Infant; D017563:Lung Diseases, Interstitial / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D011510:Proteolipids / Q000235:genetics; D011649:Pulmonary Alveolar Proteinosis / Q000175:diagnosis / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000032:analysis* / Q000172:deficiency / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000032:analysis* / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D055815:Young Adult
chemical_list: C441524:ABCA3 protein, human; D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D011498:Protein Precursors; D011510:Proteolipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human; C504003:TTF1 protein, human; D014157:Transcription Factors; C105511:surfactant protein B propeptide