title: The impact of caspase-12 on susceptibility to candidemia.
abstract: Candida is one of the leading causes of sepsis, and an effective host immune response to Candida critically depends on the cytokines IL-1β and IL-18, which need caspase-1 cleavage to become bioactive. Caspase-12 has been suggested to inhibit caspase-1 activation and has been implicated as a susceptibility factor for bacterial sepsis. In populations of African descent, CASPASE-12 is either functional or non-functional. Here, we have assessed the frequencies of both CASPASE-12 alleles in an African-American Candida sepsis patients cohort compared to uninfected patients with similar predisposing factors. African-American Candida sepsis patients (n = 93) and non-infected African-American patients (n = 88) were genotyped for the CASPASE-12 genotype. Serum cytokine concentrations of IL-6, IL-8, and IFNγ were measured in the serum of infected patients. Statistical comparisons were performed in order to assess the effect of the CASPASE-12 genotype on susceptibility to candidemia and on serum cytokine concentrations. Our findings demonstrate that CASPASE-12 does not influence the susceptibility to Candida sepsis, nor has any effect on the serum cytokine concentrations in Candida sepsis patients during the course of infection. Although the functional CASPASE-12 allele has been suggested to increase susceptibility to bacterial sepsis, this could not be confirmed in our larger cohort of fungal sepsis patients.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Internal postal code 463, P.O. Box 9101, Geert Grooteplein 8, 6500 HB, Nijmegen, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: Rosentul
authors.forename: T S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: W K
authors.initials: WK
authors.lastname: Scott
authors.forename: B D
authors.initials: BD
authors.lastname: Alexander
authors.forename: N M D
authors.initials: NM
authors.lastname: van de Geer
authors.forename: J R
authors.initials: JR
authors.lastname: Perfect
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: M D
authors.initials: MD
authors.lastname: Johnson
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002175:Candida / Q000472:pathogenicity; D058387:Candidemia / Q000235:genetics*; D053454:Caspase 12 / Q000235:genetics*; D004198:Disease Susceptibility; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D016209:Interleukin-8 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000097:blood / Q000235:genetics
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D007371:Interferon-gamma; C506444:CASP12 protein, human; D053454:Caspase 12