Association of mannose-binding lectin gene heterogeneity with severity of lung disease and survival in cystic fibrosis

Mannose-binding lectin (MBL) is a key factor in innate immunity, and lung i nfections are the leading cause of morbidity and mortality in cystic fibros is (CF). Accordingly, we investigated whether MBL variant alleles, which ar e associated with recurrent infections, might be risk factors for CF patien ts. In 149 CF patients, different MBL genotypes were compared with respect to lung function, microbiology and survival to end-stage CF (death or lung transplantation). The lung function was significantly reduced in carriers o f MBL variant alleles when compared with normal homozygotes. The negative i mpact of variant alleles on lung function was especially confined to patien ts with chronic Pseudomonas aeruginosa infection. Burkholderia cepacia infe ction was significantly more frequent in carriers of variant alleles than i n homozygotes. The risk of end-stage CF among carriers of variant alleles i ncreased 3-fold, and the survival time decreased over a 10-year follow-up p eriod. Moreover, by using a modified life table analysis, we estimated that the predicted age of survival was reduced by 8 years in variant allele car riers when compared with normal homozygotes. Presence of MBL variant allele s is therefore associated with poor prognosis and early death in patients w ith CF.