The mannan-binding lectin pathway and lung disease in cystic fibrosis—dysfunction of mannan-binding lectin-associated serine protease 2 (MASP-2) may be a major modifier

• Published in: Clinical Immunology Vol. 121; no. 3; pp. 324 - 331
• Main Authors: Olesen, H.V., Jensenius, J.C., Steffensen, R., Thiel, S., Schiøtz, P.O.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-12-2006; Elsevier
• Subjects: Biological and medical sciences; Complement activation; Cystic fibrosis; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunopathology; Mannan-binding lectin; MBL-associated serine proteases; Medical sciences; Modifier genes; Spirometry; Mannan-binding lectin; Spirometry; Cystic fibrosis; Complement activation; MBL-associated serine proteases; Modifier genes; Mannose binding lectin; Complement; Modifier gene; Immunology; Pancreatic disease; Human; Immunopathology; Lung disease; Serine endopeptidases; Respiratory disease; Enzyme; Exploration; Metabolic diseases; Genetic disease; Peptidases; Pulmonary fibrosis; Dysfunction; Digestive diseases; Hydrolases
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2006.08.014

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.