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. 2014 Nov 15;59(10):1429-36.
doi: 10.1093/cid/ciu666. Epub 2014 Aug 28.

Serum mannose-binding lectin concentration, but not genotype, is associated with Clostridium difficile infection recurrence: a prospective cohort study

Andrew Swale  1 , Fabio Miyajima  1 , Ruwanthi Kolamunnage-Dona  2 , Paul Roberts  3 , Margaret Little  1 , Nicholas J Beeching  4 , Mike B J Beadsworth  3 , Triantafillos Liloglou  5 , Munir Pirmohamed  1
Affiliations

Serum mannose-binding lectin concentration, but not genotype, is associated with Clostridium difficile infection recurrence: a prospective cohort study

Andrew Swale et al. Clin Infect Dis. .

Abstract

Background: Mannose-binding lectin (MBL) plays a key role in the activation of the lectin-complement pathway of innate immunity, and its deficiency has been linked with several acute infections. However, its role in predisposing to, or modulating disease severity in, Clostridium difficile infection (CDI) has not been investigated.

Methods: We prospectively recruited 308 CDI case patients and 145 control patients with antibiotic-associated diarrhea (AAD). CDI outcome measures were disease severity, duration of symptoms, 30-day mortality, and 90-day recurrence. Serum concentrations of MBL were determined using a commercial enzyme-linked immunosorbent assay transferred to an electrochemiluminescence-based platform. MBL2 polymorphisms were typed using a combination of pyrosequencing and TaqMan genotyping assays.

Results: The frequency of the MBL2 genetic variants was similar to that reported in other white populations. MBL serum concentrations in CDI and AAD subjects were determined by MBL2 exonic variants B, C, and D and the haplotypes (LYPB, LYQC, and HYPD). There was no difference in either MBL concentrations or genotypes between cases and controls. MBL concentration, but not genotype, was a determinant of CDI recurrence (odds ratios, 3.18 [95% confidence interval {CI}, 1.40-7.24] and 2.61 [95% CI, 1.35-5.04] at the <50 ng/mL and <100 ng/mL cutoff points, respectively; P < .001). However, neither MBL concentration nor MBL2 genotype was linked with the other CDI outcomes.

Conclusions: Serum MBL concentration did not differentiate between CDI cases and AAD controls, but among CDI cases, MBL concentration, but not genotype, was associated with CDI recurrence, indicating that MBL acts as a modulator of disease, rather than a predisposing factor.

Keywords: CDI; Clostridium difficile; MBL; disease recurrence.

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Figures

Figure 1.
Figure 1.
Schematic representation of the major MBL2 isoform and genetic polymorphisms. Polymorphisms responsible for the haplotypes that ultimately determine mannose-binding lectin (MBL) expression levels are indicated by the red arrows. *In this study, rs10556764 (6-bp deletion) was used as a proxy single-nucleotide polymorphism for rs7095891.
Figure 2.
Figure 2.
Median serum mannose-binding lectin (MBL) concentrations in relation to 3-tier grouping based on proposed expression profiles (A) and individual genotypic groups within proposed expression profiles (B). Median serum MBL concentrations were determined across previously defined expression profiles: high (YA/YA and XA/YA), intermediate (XA/XA and YA/YA), and low (XA/YO and YO/YO). Median levels were also determined for the 6 individual genotypic groups across all expression profiles. Abbreviation: MBL, mannose-binding lectin.
See this image and copyright information in PMC

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