title: The mannan-binding lectin pathway and lung disease in cystic fibrosis--disfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier.
abstract: The lectin pathway of complement activation is initiated by mannan-binding lectin (MBL) or the ficolins through the common MBL-associated serine protease-2 (MASP-2). Deficiency of MBL has been associated with poorer outcome in cystic fibrosis (CF). We investigated the MBL pathway further by analysis of the MASP-2 deficiency mutation (D105G) as well as MBL-2 genotypes. Concentrations and genotypes of MASP-2 and MBL in 109 CF patients were correlated to lung function and chronic infections. We describe the first CF patient homozygous for the mutation, a girl with extremely severe lung disease with no other precipitating factors. We suspect total MASP-2 dysfunction to be a major modifier of CF lung disease. However, heterozygosity for the D105G mutation of MASP-2 had no correlation to MBL pathway function or poor lung function. Lung function was higher in the MBL deficiency determining genotypes (XA/YO+YO/YO) than in the other genotypes.
authors.affiliation: Department of Pediatrics A, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark. hvo@dadlnet.dk
authors.forename: H V
authors.initials: HV
authors.lastname: Olesen
authors.forename: J C
authors.initials: JC
authors.lastname: Jensenius
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.forename: S
authors.initials: S
authors.lastname: Thiel
authors.forename: P O
authors.initials: PO
authors.lastname: Schiøtz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood*; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000235:genetics / Q000378:metabolism*
chemical_list: D037601:Mannose-Binding Lectin; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases