title: Serum mannose-binding lectin concentration, but not genotype, is associated with Clostridium difficile infection recurrence: a prospective cohort study.
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.
authors.affiliation: The Wolfson Centre for Personalised Medicine, University of Liverpool The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Andrew
authors.initials: A
authors.lastname: Swale
authors.affiliation: The Wolfson Centre for Personalised Medicine, University of Liverpool The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Fabio
authors.initials: F
authors.lastname: Miyajima
authors.affiliation: Department of Biostatistics, University of Liverpool.
authors.forename: Ruwanthi
authors.initials: R
authors.lastname: Kolamunnage-Dona
authors.affiliation: The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Paul
authors.initials: P
authors.lastname: Roberts
authors.affiliation: The Wolfson Centre for Personalised Medicine, University of Liverpool The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Margaret
authors.initials: M
authors.lastname: Little
authors.affiliation: The Royal Liverpool and Broadgreen University Hospitals NHS Trust Liverpool School of Tropical Medicine Health Protection Unit in Gastrointestinal Infections, National Institute for Health Research.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Beeching
authors.affiliation: The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Mike B J
authors.initials: MB
authors.lastname: Beadsworth
authors.affiliation: Cancer Research Centre, University of Liverpool, United Kingdom.
authors.forename: Triantafillos
authors.initials: T
authors.lastname: Liloglou
authors.affiliation: The Wolfson Centre for Personalised Medicine, University of Liverpool The Royal Liverpool and Broadgreen University Hospitals NHS Trust.
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016360:Clostridioides difficile; D003015:Clostridium Infections / Q000097:blood* / Q000382:microbiology; D015897:Comorbidity; D004761:Enterocolitis, Pseudomembranous / Q000097:blood* / Q000209:etiology / Q000382:microbiology; D005260:Female; D005787:Gene Frequency; D023061:Gene Order; D056426:Genetic Loci; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D020033:Protein Isoforms; D012008:Recurrence; D012016:Reference Values
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D020033:Protein Isoforms
keywords: CDI; Clostridium difficile; MBL; disease recurrence