The results from the studies were each independently significant,

The results from the studies were each independently significant, with P values ranging from <0·01

selleck chemical to 0·04. Because each study was reported as independently significant, we did not perform a formal meta-analysis on these data. Serum MBL-level data from active TB versus controls are shown graphically in Fig. 4. The consistent finding of higher MBL serum levels in patients with TB than uninfected controls suggests strongly that high MBL levels are associated with active TB disease. Our meta-analysis of accessible, published data has demonstrated no statistically significant association between MBL2 genotype and pulmonary TB infection. Review of studies considering MBL levels has, however, demonstrated a consistent increase in MBL levels in patients with tuberculosis. There are a number find more of mechanisms that could account for this discrepancy between MBL levels and MBL2 genotype and their associations with TB. First, MBL2 genotype involving structural gene polymorphisms alone is a poor predictor of serum MBL

levels. Therefore the direct assessment of MBL phenotype through measurement of blood levels may be the best way to reveal an association between MBL sufficiency and predisposition to TB from the available data. Perhaps the most plausible explanation, however, is that MBL is elevated in active tuberculosis infection as part of an acute-phase reaction. If this is so, then MBL would not appear to be involved significantly in host susceptibility to tuberculosis infection. In an attempt to investigate these alternative explanations, we performed additional ad hoc subgroup analysis on studies that reported complete MBL2 genotypic profile, including promoter regions. The small sample of this subgroup analysis does

not permit significant conclusions to be drawn from the lack of association between complete MBL2 genotype and TB susceptibility; however, were such results repeated in Amylase larger studies it may provide additional support for the hypothesis that MBL is not involved in tuberculosis infection and elevated MBL levels seen in patients with TB represent its acute-phase response. Although some studies have suggested that MBL may not have a significant overall acute-phase response, patients with wild-type MBL2 genotypes have been generally found to have raised MBL levels in this setting [30]. This is consistent with the study populations included in this meta-analysis, where the proportion of patients homozygous for wild-type MBL2 accounted for 92% of the populations where both MBL levels and genotypes were available. In these populations, therefore, the acute-phase properties of MBL are likely to be dominant. This contrasts with other studies of the acute-phase change seen in septic patients who had a higher frequency of MBL2 variant alleles [36]. Support for this conclusion can be seen in studies where MBL levels have been studied in the acute-phase reaction. Thiel et al.

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