title: Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2 alleles.
abstract: Mannose-binding lectin has recently been identified as a modifier of severity in cystic fibrosis, although studies have produced differing results and the mechanism of action remains unclear. The current authors have studied large cohorts of adults (n=298) and children (n=260) to explore this apparent relationship further. Adults with two structural mutations, but not heterozygotes, had significantly reduced lung function and oxygen saturations, more frequent hospital admissions and raised systemic inflammatory markers. This was not related to increased rates of infection with Pseudomonas aeruginosa, and there was no increased susceptibility to Burkholderia cepacia. None of these findings was mirrored in the paediatric cohort. In conclusion, severe mannose-binding lectin deficiency appears to be detrimental to cystic fibrosis adults, although heterozygotes are not affected. It is suggested that this is not related to impaired complement-mediated bacterial killing, and a link with the host inflammatory response is hypothesised. If mannose-binding lectin replacement is developed as a new approach to treatment for this disease, the present study would suggest that the small group of severely deficient patients with two structural mutations may be the group to benefit.
authors.affiliation: Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, Sydney St, London, SW3 6NP, UK. j.c.davies@imperial.ac.uk
authors.forename: J C
authors.initials: JC
authors.lastname: Davies
authors.forename: M W
authors.initials: MW
authors.lastname: Turner
authors.forename: N
authors.initials: N
authors.lastname: Klein
mesh_terms: D000328:Adult; D019121:Burkholderia Infections / Q000150:complications; D016956:Burkholderia cepacia; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006720:Homozygote; D006801:Humans; D008168:Lung / Q000503:physiopathology*; D008297:Male; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000235:genetics*; D009154:Mutation; D011552:Pseudomonas Infections / Q000150:complications
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin