Mannose-binding lectin genotype and serum levels in patients with chronic and allergic pulmonary aspergillosis.
Several studies suggest mannose-binding lectin (MBL) deficiency is associated with various manifestations of aspergillosis. MBL serum levels and function are genetically determined, but levels rise during inflammation. We address the relative frequency of deficient genotypes, the relationship between serum level and genotype and both age and disease manifestations in patients with chronic pulmonary (CPA) and allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). DNA was extracted from blood samples, and MBL2 genotyping was performed using the INNO-LiPA MBL2 kit. Serum MBL concentrations were determined using ELISA. One hundred and eight patients were evaluated, 70 (65%) with CPA, 38 (35%) with allergic disease (ABPA, SAFS or undefined) and 13 (12%) had both CPA and ABPA. The mean MBL serum level was 1849 μg L(-1) and did not differ between groups. Forty subjects (37%) had exon 1 genotypes producing nonfunctional MBL (A/B, A/C, A/D and O/O), a frequency not different from published normal controls. A/A subjects with CPA had higher levels (2981 μg L(-1)) compared with allergic A/A subjects (2202 μg L(-1)) (pc0.012). No single haplotype, genotype or allele was significantly related to any aspergillosis phenotype. Worse breathlessness was associated with higher MBL levels among A/A subjects (P = 0.009) and conversely nonfunctional genotypes. Mean MBL values were higher in those with an Medical Research Council (MRC) breathlessness score of 5 compared with those with and MRC score of 1 (P = 0.023). A/A allergic subjects (n = 27) in this study were ≈ 11 years younger than allergic A/O subjects (n = 11, P = 0.02). Subjects with worse respiratory status or more severe CPA had higher MBL serum levels (P = 0.023; P = 0.034). Bronchiectasis was not associated with MBL levels in CPA or allergic aspergillosis. MBL genotype and serum level modulate progression of aspergillosis.
The National Aspergillosis Centre, The University Hospital of South Manchester, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
E
E
Harrison
A
A
Singh
J
J
Morris
N L
NL
Smith
M G
MG
Fraczek
C B
CB
Moore
D W
DW
Denning
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000235:genetics*; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D037601:Mannose-Binding Lectin / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055732:Pulmonary Aspergillosis / Q000097:blood / Q000235:genetics*
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin