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.
Mannose binding lectin (MBL) gene and promoter-region polymorphisms contribute to a reduction in the levels of circulating MBL in a number of ways. Promoter polymorphisms affect the levels of MBL produced, whilst structurally encoding mutations cause non-functional protein to be assembled and subsequently degraded. MBL is important as a protein of the innate immune system in both the clearance of potential pathogens and the activation of the complement cascade. Using variations of SSP-PCR amplifications and SSO probing techniques, we have produced MBL-polymorphism haplotype and genotype profiles of a series of high-level MBL-producing, low-level MBL-producing and random individuals taken from a population of 800 UK Caucasoid controls. Structurally encoding mutant alleles were more frequent within the low-level producing cohort when compared to both high-level producers and the randomly selected sample. However, not all low-level producers could be accounted for by the possession of low-level encoding haplotypes. This may be due to the presence of additional, undetected polymorphisms governing MBL production, or another external factor that may influence the transcriptional regulation of the gene.
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