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

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.

• Authors: 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
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 54 Issue 4 Pg. 502-10 (Feb 15 2012) ISSN: 1537-6591 [Electronic] United States
• PMID: 22144535 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines

Topics

• Adult
• Aged
• Candidiasis, Invasive (immunology, mortality, pathology)
• Cells, Cultured
• Cohort Studies
• Cytokines (genetics, metabolism)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• Leukocytes, Mononuclear (immunology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prospective Studies
• Treatment Outcome