Cytokine Gene Polymorphisms and the Outcome of Invasive Candidiasis: A Prospective Cohort Study

Background. Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes o...

Full description

Saved in:
Bibliographic Details
Published in:Clinical infectious diseases 2012-02, Vol.54 (4), p.502-510
Main Authors: Johnson, Melissa D., Plantinga, Theo S., van de Vosse, Esther, Edwards, Digna R. Velez, Smith, P. Brian, Alexander, Barbara D., Yang, John C., Kremer, Dennis, Laird, Gregory M., Oosting, Marije, Joosten, Leo A. B., van der Meer, Jos W. M., van Dissel, Jaap T., Walsh, Thomas J., Perfect, John R., Kullberg, Bart-Jan, Scott, William K., Netea, Mihai G.
Format: Article
Language:English
Subjects:
Adult
Aged
Alleles
and Commentaries
ARTICLES AND COMMENTARIES
Biological and medical sciences
Blood
Candida
Candidemia
Candidiasis, Invasive - immunology
Candidiasis, Invasive - mortality
Candidiasis, Invasive - pathology
Cells
Cells, Cultured
Cohort Studies
Cytokines
Cytokines - genetics
Cytokines - secretion
Female
Fungal infections
Fungemia
Gene expression
Genetic Association Studies
Genetic Predisposition to Disease
Health outcomes
Humans
Infections
Infectious diseases
Invasive candidiasis
Leukocytes, Mononuclear - immunology
Male
Medical genetics
Medical sciences
Middle Aged
Polymorphism
Polymorphism, Single Nucleotide
Prospective Studies
Treatment Outcome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background. Candida bloodstream infections cause significant morbidity and mortality among hospitalized patients. Although clinical and microbiological factors affecting prognosis have been identified, the impact of genetic variation in the innate immune responses mediated by cytokines on outcomes of infection remains to be studied. Methods. A cohort of 338 candidemia patients and 351 noninfected controls were genotyped for singlenucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, ILlβ, IL8) and 1 cytokine receptor gene (IL12RB1). The association of SNPs with both candidemia susceptibility and outcome were assessed. Concentrations of pro- and antiinflammatory cytokines were measured in in vitro peripheral blood mononuclear cell stimulation assays and in serum from infected patients. Results. None of the cytokine SNPs studied were associated with susceptibility to candidemia. Persistent fungemia occurred in 13% of cases. In the multivariable model, persistent candidemia was significantly associated with (odds ratio [95% confidence interval]): total parenteral nutrition (2.79 [1.26-6.17]), dialysis dependence (3.76 [1.46-8.64]), and the SNPs JL10 rs1800896 (3.45 [1.33-8.93]) and IL12B rs41292470 (5.36 [1.51-19.0]). In vitro production capacity of interleukin-10 and interferon-γ was influenced by these polymorphisms, and significantly lower proinflammatory cytokine concentrations were measured in serum from patients with persistent fungemia. Conclusions. Polymorphisms in IL10 and IL12B that result in low production of proinflammatory cytokines are associated with persistent fungemia in candidemia patients. This provides insights for future targeted management strategies for patients with Candida bloodstream infections.
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cir827