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Mannose-binding lectin gene polymorphisms as a susceptibility factor for chronic necrotizing pulmonary aspergillosis
D J Crosdale1, K V Poulton, W E Ollier
1Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester, United Kingdom. dan.crosdale@sheffield.ac.uk
Abstract:
It was investigated whether a deficiency of mannose-binding lectin (MBL), which binds Aspergillus species avidly in vitro, could account for chronic necrotizing pulmonary aspergillosis (CNPA), which is seen most commonly in nonimmunocompromised patients. Blood samples were obtained from 11 patients (10 white) with CNPA and were compared with blood samples from 82 white control subjects. MBL haplotype profiles were determined by polymerase chain reaction, using sequence-specific primers and sequence-specific oligonucleotide probing techniques. Seven of the 10 white patients with CNPA had MBL haplotypes that encode for low levels of the protein, compared with 25.6% of the white control subjects (P=.004). Presence of the codon 52 mutation was particularly common in patients with CNPA (P=.015), which suggests a greater involvement of this mutation.
Insights
A mannose-binding lectin (MBL) deficiency may explain chronic necrotizing pulmonary aspergillosis (CNPA) in non-immunocompromised patients. Low MBL protein levels and specific mutations were more common in CNPA patients than controls.
Area of Science:
- Immunology
- Pulmonology
- Genetics
Background:
- Mannose-binding lectin (MBL) binds Aspergillus species in vitro.
- Chronic necrotizing pulmonary aspergillosis (CNPA) often affects non-immunocompromised individuals.
- The role of MBL deficiency in CNPA pathogenesis is unclear.
Purpose of the Study:
- To investigate if MBL deficiency is associated with CNPA.
- To determine MBL haplotype profiles in CNPA patients and controls.
Main Methods:
- Blood samples from 11 CNPA patients and 82 controls were analyzed.
- Polymerase chain reaction with sequence-specific primers and oligonucleotide probing was used.
- MBL haplotype profiles, including codon 52 mutation, were determined.
Main Results:
- Seven of ten white CNPA patients (70%) had MBL haplotypes encoding low protein levels.
- This contrasts with 25.6% of white control subjects (P=.004).
- The MBL codon 52 mutation was significantly more frequent in CNPA patients (P=.015).
Conclusions:
- MBL deficiency is associated with chronic necrotizing pulmonary aspergillosis.
- Low MBL levels and the codon 52 mutation may contribute to CNPA development.
- Further research into MBL's role in fungal lung infections is warranted.