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Mannose-binding Lectin Concentrations and Susceptibility to Respiratory Infections
Abstract and Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center; Clinical Professor, Stanford University, School of Medicine, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Synopsis: Serum mannose-binding lectin (MBL) concentrations and MBL2 gene polymorphisms were examined in 473 Finnish military recruits. An MBL serum level below the median was a risk factor for respiratory infections. Of the six single-nucleotide polymorphisms (SNPs) examined in the MBL2 gene, a promoter Y/Y genotype was associated with infections.
Source: Rantala A, et al. Mannose-binding lectin concentrations, MBL2 polymorphisms, and susceptibility to respiratory tract infections in young men. J Infect Dis. 2008;198:1247-1253.
This exploratory study investigated the relationship between respiratory infections and MBL serum concentrations and the presence of six SNPs in the MBL2 gene promoter region (alleles H/L, X/Y, and P/Q) and exon 1 (wild type allele A and variant alleles B, C, and D) using real-time PCR. In this study, 111 Finnish military recruits with asthma and 362 recruits without asthma were studied. Paired serum samples were obtained at the beginning and end of service (which was generally between six and 12 months duration), as well as paired samples for each infectious episode. No promoter region or exon 1 genotypes were associated with asthma. However, there was a significant association between the frequency of respiratory tract infections in subjects with MBL levels above and below the mean concentration of 1087.5 ng/mL. Thirty percent of subjects under the mean vs. 16% of subjects above the mean MBL concentration had ≥ 2 infectious episodes during their term of service, and were associated with an odds ratio (OR) of 2.5 adjusted for asthma status. Similarly, a Y/Y MBL2 promoter genotype variant was associated with an OR of 2.3 for infection. A trend toward association between exon 1 alleles associated with low levels of MBL was seen but did not reach statistical significance.
Over the last 20 years, understanding of the importance of various components of the innate immune system has grown. MBL is an important serum protein that selectively recognizes the carbohydrate patterns of micro-organisms, or infected cells, then promotes opsonization directly, as well as by activation of the alternate complement pathway through the lectin system. While this study is small, the associations between MBL levels, MBL2 promoter region polymorphisms, and respiratory infections observed in this relatively homogenous population of young Finnish men are intriguing. While clearly many factors play a role in individual host susceptibility to respiratory infections (and likely vary in relative importance with different pathogens), this study sheds light on the importance of MBL in defense against common respiratory pathogens in a population of healthy individuals. Clearly, this is a fruitful area for research, and data from larger studies are eagerly awaited.