TY - JOUR
T1 - Serum mannose-binding lectin concentration, but not genotype, is associated with Clostridium difficile infection recurrence
T2 - a prospective cohort study
AU - Swale, Andrew
AU - Miyajima, Fabio
AU - Kolamunnage-Dona, Ruwanthi
AU - Roberts, Paul
AU - Little, Margaret
AU - Beeching, Nicholas J
AU - Beadsworth, Mike B J
AU - Liloglou, Triantafillos
AU - Pirmohamed, Munir
N1 - © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.
PY - 2014/11/15
Y1 - 2014/11/15
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Case-Control Studies
KW - Clostridioides difficile
KW - Clostridium Infections/blood
KW - Comorbidity
KW - Enterocolitis, Pseudomembranous/blood
KW - Female
KW - Gene Frequency
KW - Gene Order
KW - Genetic Loci
KW - Genotype
KW - Haplotypes
KW - Humans
KW - Male
KW - Mannose-Binding Lectin/blood
KW - Middle Aged
KW - Patient Outcome Assessment
KW - Polymorphism, Genetic
KW - Prospective Studies
KW - Protein Isoforms
KW - Recurrence
KW - Reference Values
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U2 - 10.1093/cid/ciu666
DO - 10.1093/cid/ciu666
M3 - Article (journal)
C2 - 25170052
SN - 1058-4838
VL - 59
SP - 1429
EP - 1436
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 10
ER -