Concordance of MBL protein concentrations, functional activities, and genotypes in a healthy control population

Abstract

RATIONALE: MBL is a soluble oligomeric pattern recognition molecule that constitutes an important element in innate immune defense against a broad range of microorganisms. The binding of MBL to sugar motifs occurring on the surface of these microorganisms leads to the recruitment of MBL associated serine proteases (MASPs), which in complex with MBL activate complement via the MBL pathway. MBL-MASP complex deficiencies have been described in individuals and are mainly attributed to genetic polymorphisms. Individuals with MBL-MASP complex deficiencies have reduced or deficient complement activation via the MBL pathway, and in some, this condition leads to severe or recurrent infections. METHODS: In this study, the MBL protein concentration, functional activity and genotype of 30 individuals in a healthy control population were determined by ELISA, C4b deposition and real-time PCR, respectively. RESULTS: This study indicates that 90% (18/20) of individuals without a structural variant in exon 1 of the mbl2 gene have sufficient MBL protein concentrations (>1000 ng/mL) and function. The remaining 10% (2/20) of individuals without a structural variant who have sufficient MBL protein concentrations were determined to be deficient in MBL function. All individuals (10/10) with a structural variant have MBL levels that are characterized as deficient (<100 ng/mL) or reduced (<1000 ng/mL) and have deficient MBL function. CONCLUSIONS: The MBL protein concentration, functional activity and genotype data from 30 healthy controls were observed to be generally concordant. However, these data would suggest that determining MBL concentration, functional activity or genotype alone, is not sufficient to fully evaluate an individual's MBL status.