Abstract
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. 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. 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. 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.
Highlights
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
MBL concentration, but not genotype, was a determinant of Clostridium difficile infection (CDI) recurrence
Serum MBL concentration did not differentiate between CDI cases and associated diarrhea (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
Summary
We prospectively recruited 308 CDI case patients and 145 control patients with antibiotic-associated diarrhea (AAD). Serum concentrations of MBL were determined using a commercial enzyme-linked immunosorbent assay transferred to an electrochemiluminescence–based platform. Patients were eligible for inclusion if they had healthcare-associated diarrhea (defined as ≥3 liquid stools passed in the 24 hours preceding assessment), an onset after being in hospital for >48 hours, and recent exposure to either antimicrobials and/or proton pump inhibitors (PPIs). Using criteria previously described [27], 308 patients with CDI (cases) and 145 control patients with antibiotic-associated diarrhea (AAD) were classified based on toxin enzyme-linked immunosorbent assay (ELISA) test (TOX A/B II, Techlab, Blacksburg, Virginia), microbiological culture, and clinical diagnosis made by independent clinicians. Admission, and clinical history was collected for each patient. Ethical approval was obtained from the Liverpool Research Ethics Committee (reference number 08/H1005/ 32), and each patient provided written informed consent prior to recruitment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
