title: Mannose-binding lectin deficiency and disease severity in non-cystic fibrosis bronchiectasis: a prospective study.
abstract: BACKGROUND
  Mannose-binding lectin (MBL) is a key component of innate immunity. MBL deficiency is common (10-30% of the general population depending on the definition used) and has been associated with disease progression in cystic fibrosis. We aimed to assess the effect of MBL deficiency on disease severity in non-cystic fibrosis bronchiectasis.
  
  
  METHODS
  We recruited patients with non-cystic fibrosis bronchiectasis and age-matched and sex-matched controls at a specialist bronchiectasis clinic in Edinburgh, UK. We assessed MBL function with genotyping (low-expressing genotype [deficiency] defined as homozygosity for exon 1 mutations [YO/YO] or compound heterozygosity [XA/YO]; YA/YO and XA/XA genotypes were defined as intermediate-expressing with all other genotypes defined as high-expressing) and serum measurements (deficiency defined with two parameters: <500 ng/mL or <200 ng/mL). We assessed rates of exacerbation, chronic bacterial colonisation, and lung function during 4 years of follow-up.
  
  
  RESULTS
  We included 470 patients with bronchiectasis and 414 controls. MBL genotype frequencies and MBL serum concentrations did not differ between patients and controls. 55 (12%) patients with bronchiectasis had low-expressing genotypes. These patients had a mean of 2·7 exacerbations per year (SD 1·8), compared with 1·9 per year (1·2) for 135 patients with intermediate-expressing genotypes and 1·9 per year (1·3) for 280 patients with high-expressing genotypes (p<0·0001). Chronic colonisation with bacteria was most frequent in patients with low-expressing genotypes (47 [85%] patients vs 82 [61%] patients with intermediate-expressing genotypes and 183 [65%] patients with high-expressing genotypes; p=0·0041); especially P aeruginosa colonisation (19 [35%] patients vs 13 [10%] patients and 36 [13%] patients; p<0·0001). Patients with low-expressing genotypes were more likely to be admitted to hospital for severe exacerbations during follow-up (27 [49%] patients vs 42 [31%] patients and 87 [31%] patients; p=0·032). Patients with low-expressing genotypes also had increased scores for radiological severity and worse quality of life compared with the other two groups. MBL serum deficiency (<200 ng/mL) was associated with increased exacerbations, hospital admissions, and radiological severity. When <500 ng/mL was used as the definition of deficiency, the associations with exacerbation frequency and radiological severity were no longer significant.
  
  
  CONCLUSIONS
  MBL might be an important modifier of disease severity in non-CF bronchiectasis.
  
  
  BACKGROUND
  UK Medical Research Council, UK Chief Scientists Office.
authors.affiliation: Tayside Respiratory Research Group, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK. Electronic address: jameschalmers1@nhs.net.
authors.forename: James D
authors.initials: JD
authors.lastname: Chalmers
authors.affiliation: MRC Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McHugh
authors.affiliation: School of Medicine and Veterinary Medicine, Cystic Fibrosis Group, and Centre for Infectious Diseases, University of Edinburgh, Edinburgh, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Doherty
authors.affiliation: Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Maeve P
authors.initials: MP
authors.lastname: Smith
authors.affiliation: School of Medicine and Veterinary Medicine, Cystic Fibrosis Group, and Centre for Infectious Diseases, University of Edinburgh, Edinburgh, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Govan
authors.affiliation: Scottish National Blood Transfusion Service, Edinburgh, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Kilpatrick
authors.affiliation: Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Adam T
authors.initials: AT
authors.lastname: Hill
mesh_terms: D000368:Aged; D058491:Bacterial Load; D001987:Bronchiectasis / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D018450:Disease Progression; D015987:Effect Modifier, Epidemiologic; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000150:complications*; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D012129:Respiratory Function Tests / Q000379:methods; D012720:Severity of Illness Index; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D037601:Mannose-Binding Lectin