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Pparγ Expression in T Cells as a Prognostic Marker of Sepsis
Marco Brenneis1, Ramin Aghajaanpour, Tilo Knape
1*Institute of Biochemistry I-Pathobiochemistry, Faculty of Medicine, Goethe-University Frankfurt †Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP ‡Department of Anaethesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt §Department of Nephrology, Medical Clinic III, University Hospital Frankfurt, Frankfurt, Germany.
Abstract:
Translating murine data to the human situation, we proposed that the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in T cells from septic patients correlates with clinical outcome. In this preliminary report, we analyzed PPARγ mRNA expression in CD3 T cells derived from blood of a very small number of septic patients (n = 18) on various days up to 2 weeks after the initial diagnosis. CD3 T cell count was determined by flow cytometry. T cells from n = 11 healthy donors were included as controls. Maximal PPARγ mRNA expression was observed on the day of sepsis diagnosis (day 0; 5,896 ± 1,523 copies PPARγ mRNA/25 ng mRNA, P < 0.05 vs. controls). In contrast, the number of CD3 T cells was significantly decreased in septic patients compared with healthy controls (296 ± 31 vs. 1,803 ± 134 T cells/μL blood, P < 0.001). Setting two arbitrary limits: patients with a PPARγ expression in T cells higher than 7,000 copies/25 ng mRNA, of whom five of six patients died during the ICU stay, and patients with a T cell count below 100 T cells/μL blood, of whom five of eight patients died, we identified a correlation between sepsis survival and low T cell number, paired with high T cell-specific PPARγ expression. Among all 18 sepsis patients, four fulfilled the criteria for both arbitrary settings and all four of these patients subsequently died. We suggest that both high PPARγ expression in T cells and low absolute T cell number in blood of septic patients may have the potential as a new prognostic marker for a poor sepsis outcome.
Insights
High peroxisome proliferator-activated receptor gamma (PPARγ) expression in T cells and low T cell counts in septic patients may indicate a poor prognosis. This suggests PPARγ and T cell counts could be novel prognostic markers for sepsis survival.
Area of Science:
- Immunology
- Molecular Biology
- Critical Care Medicine
Background:
- Sepsis is a life-threatening condition characterized by dysregulated host response to infection.
- Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in immune regulation, but its role in sepsis prognosis is unclear.
- Murine studies suggest a link between PPARγ and sepsis outcomes, necessitating translation to human data.
Purpose of the Study:
- To investigate the correlation between PPARγ expression in T cells and clinical outcomes in septic patients.
- To evaluate the potential of PPARγ mRNA levels and CD3 T cell counts as prognostic markers for sepsis.
Main Methods:
- Analysis of PPARγ mRNA expression in CD3 T cells from 18 septic patients and 11 healthy controls.
- Quantification of T cell counts using flow cytometry.
- Correlation analysis between PPARγ levels, T cell counts, and patient survival during ICU stay.
Main Results:
- Maximal PPARγ mRNA expression was observed on the day of sepsis diagnosis (5,896 ± 1,523 copies/25 ng mRNA), significantly higher than controls (P < 0.05).
- Septic patients exhibited significantly decreased CD3 T cell counts (296 ± 31 cells/μL) compared to healthy controls (1,803 ± 134 cells/μL, P < 0.001).
- Patients with high PPARγ expression (>7,000 copies) or low T cell counts (<100 cells/μL) showed increased mortality. Four patients meeting both criteria died.
Conclusions:
- High PPARγ expression in T cells and low absolute T cell counts in septic patients are associated with poor clinical outcomes.
- These parameters show potential as novel prognostic biomarkers for predicting sepsis survival.
- Further validation in larger cohorts is warranted to establish their clinical utility.
