TY - JOUR T1 - Impaired pulmonary status in cystic fibrosis adults with two mutated <em>MBL-2</em> alleles JF - European Respiratory Journal JO - Eur Respir J SP - 798 LP - 804 DO - 10.1183/09031936.04.00055404 VL - 24 IS - 5 AU - J.C. Davies AU - M.W. Turner AU - N. Klein AU - and the London MBL CF Study Group The London MBL CF Study Group: C. Booth, M. Johnson, N. Shen, K. Fidler, S. Sharma, J. Burgess, A. Bush, D.M. Geddes, E.W.F.W. Alton. Y1 - 2004/11/01 UR - http://erj.ersjournals.com/content/24/5/798.abstract N2 - 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. This work was supported by the Cystic Fibrosis Research Trust, by a Wellcome Trust Senior Clinical Fellowship (E.W.F.W. Alton), and a Wellcome Trust Clinical Fellowship (K. Fidler). Research at the Institute of Child Health and Great Ormond Street for Children National Health Service (NHS) Trust benefits from research and development funding received from the UK NHS executive. Consumables for this study were funded in part by NatImmune A/S, Copenhagen, Denmark. M.W. Turner and N. Klein are consultants for this company, which is developing a recombinant form of mannose-binding lectin. ER -