Dataset Information

Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

ABSTRACT:

Objective

Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-?) plays an important role in inflammation, this work assessed IFN-? single nucleotide polymorphism (SNPs) that may be associated with sepsis.

Methods

A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation) and SOFA (sepsis-related organ failure assessment) scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705), -764G/C (rs2069707), +874A/T (rs2430561) and +3234C/T (rs2069718), were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values), odds ratios (OR) and 95% confidence intervals (CIs) were calculated.

Results

No mutations in the IFN-? -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD) (r(2)?=?0.894). The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.

Conclusion

Our results suggest that functional IFN-? SNPs and their haplotypes are associated with pneumonia-induced sepsis.

SUBMITTER: Wang D

PROVIDER: S-EPMC3901723 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

Wang Ding D Zhong Xuan X Huang Dongjian D Chen Rui R Bai Guibin G Li Qing Q Yu Bolan B Fan Yong Y Sun Xiaofang X

PloS one 20140124 1

<h4>Objective</h4>Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ) plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs) that may be associated with sepsis.<h4>Methods</h4>A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinic ...[more]

PMID: 24475220

Similar Datasets

Project description:BACKGROUND:The sepsis-induced immunodepression contributes to impaired clinical outcomes of various stress conditions. This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells. Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFN?) is one. It is of paramount relevance to obtain clinical information on optimal timing of the IFN?-treatment, -tolerance, -effectiveness and outcome before performing a RCT. We describe the effects of IFN? in a cohort of 18 adult and 2 pediatric sepsis patients. METHODS:In this open-label prospective multi-center case-series, IFN? treatment was initiated in patients selected on clinical and immunological criteria early (<?4?days) or late (>?7?days) following the onset of sepsis. The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality. RESULTS:In 15 out of 18 patients IFN? treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)]. Plasma levels of IL-6 464 [201-770] to 108 (89-140) ng/mL (p?=?0.04) and IL-10 from IL-10 from 29 [12-59] to 9 [1-15] pg/mL decreased significantly. Three patients who received IFN? early after ICU admission (<4?days) died. The other patients had a rapid clinical improvement assessed by the SOFA score and bacterial cultures that were repeatedly positive became negative. The 2 pediatric cases improved rapidly, but 1 died for hemorrhagic complication. CONCLUSION:Guided by clinical and immunological monitoring, adjunctive immunotherapy with IFN? appears well-tolerated in our cases and improves immune host defense in sepsis induced immuno suppression. Randomized clinical studies to assess its potential clinical benefit are warranted.

Dataset Information

Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

Objective

Methods

Results

Conclusion

Publications

Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

Similar Datasets

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