Cytokine gene polymorphisms and the outcome of invasive candidiasis: A prospective cohort study

Melissa D. Johnson, Theo S. Plantinga, Esther Van De Vosse, Digna R. Velez Edwards, P. Brian Smith, Barbara D. Alexander, John C. Yang, Dennis Kremer, Gregory M. Laird, Marije Oosting, Leo A.B. Joosten, Jos W.M. Van Der Meer, Jaap T. Van Dissel, Thomas J. Walsh, John R. Perfect, Bart Jan Kullberg, William K. Scott, Mihai G. Netea

Research output: Contribution to journalArticlepeer-review

Abstract

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 single-nucleotide polymorphisms (SNPs) in 6 cytokine genes (IFNG, IL10, IL12B, IL18, IL1β, 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 IL10 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.

Original languageEnglish (US)
Pages (from-to)502-510
Number of pages9
JournalClinical Infectious Diseases
Volume54
Issue number4
DOIs
StatePublished - Feb 15 2012

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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