Altered OXPHOS potential in ascites immune cells is linked to CD4 T-cell exhaustion and a higher risk of spontaneous bacterial peritonitis in cirrhosis
- 1Department of Hepatology & Gastroenterology, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte
- 2Section of Hepatology and Gastroenterology, Department of Internal Medicine, Knappschaft Kliniken-University Hospital Bochum, Ruhr University Bochum
Abstract
Background and aims: Ascites marks advanced cirrhosis and increases the risk of complications including SBP. Systemic inflammation in liver disease is well characterized, but the immunometabolic properties of the peritoneal compartment remain undefined. This study evaluated the metabolic characteristics of ascites-derived immune cells.
Method: Matched blood and ascites samples from patients with cirrhosis without SBP (n = 21) were analyzed. OXPHOS and glycolysis were assessed using the Seahorse XFe96, lactate concentrations were measured, and immune cell subsets were characterized by spectral flow cytometry.
Results: T cells were the dominant subset in ascites and blood (58.2% vs. 49%, p=0.0822) and CD4 ⁺ T cells represented the predominant subset (57.3% vs. 64.6%, p=0.026). Ascites-derived MNCs exhibited higher basal and maximal respiration than blood-counterparts (4.4 vs 3.6, p = 0.033 and 20 vs 13.3 pmol O ₂ /min/µg protein, p=0.004). Proton leak was increased in ascites (0.7 vs 0.4 pmol O ₂ /min/µg protein, p<0.0001). OXPHOS potential was increased in ascites (365.9% vs. 290.9%, p<0.001) while glycolytic potential was reduced (208.0% vs. 286.8%, p < 0.001), corroborated by lower ascitic lactate concentrations (1.9 vs. 3.8 mM/L, p<0.001). Patients with low ascites OXPHOS potential had higher risk of developing SBP (p = 0.016). CD4 ⁺ T cells in ascites showed elevated PD-1 expression (36.9% vs. 14.7%, p < 0.0001), associated with reduced OXPHOS potential (407.1% vs. 324.6% in PD-1-low vs. PD-1-high cells, p = 0.036).
Conclusion: Peritoneal immune cells exhibit a dissociated phenotype—elevated oxidative activity alongside features of immune exhaustion—reflecting their distinct role in immune regulation within the peritoneal environment.
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BibTeX
@article{cosgun2026altered,
title = {{Altered OXPHOS potential in ascites immune cells is linked to CD4 T-cell exhaustion and a higher risk of spontaneous bacterial peritonitis in cirrhosis}},
author = {Hasan Tarik Cosgun and Pavitra Kumar and Ingrid Wei Zhang and Linda Hammerich and Virein Sudheer and Charalampos Pavlidis and Juan Wang and Hannah Schwarz and Frank Tacke and Ali Canbay and Cornelius Engelmann},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1853973},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1853973/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Altered OXPHOS potential in ascites immune cells is linked to CD4 T-cell exhaustion and a higher risk of spontaneous bacterial peritonitis in cirrhosis
AU - Hasan Tarik Cosgun
AU - Pavitra Kumar
AU - Ingrid Wei Zhang
AU - Linda Hammerich
AU - Virein Sudheer
AU - Charalampos Pavlidis
AU - Juan Wang
AU - Hannah Schwarz
AU - Frank Tacke
AU - Ali Canbay
AU - Cornelius Engelmann
PY - 2026
DA - 2026/10/06
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1853973
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1853973/full
AB - Background and aims: Ascites marks advanced cirrhosis and increases the risk of complications including SBP. Systemic inflammation in liver disease is well characterized, but the immunometabolic properties of the peritoneal compartment remain undefined. This study evaluated the metabolic characteristics of ascites-derived immune cells. Method: Matched blood and ascites samples from patients with cirrhosis without SBP (n = 21) were analyzed. OXPHOS and glycolysis were assessed using the Seahorse XFe96, lactate concentrations were measured, and immune cell subsets were characterized by spectral flow cytometry. Results: T cells were the dominant subset in ascites and blood (58.2% vs. 49%, p=0.0822) and CD4 ⁺ T cells represented the predominant subset (57.3% vs. 64.6%, p=0.026). Ascites-derived MNCs exhibited higher basal and maximal respiration than blood-counterparts (4.4 vs 3.6, p = 0.033 and 20 vs 13.3 pmol O ₂ /min/µg protein, p=0.004). Proton leak was increased in ascites (0.7 vs 0.4 pmol O ₂ /min/µg protein, p<0.0001). OXPHOS potential was increased in ascites (365.9% vs. 290.9%, p<0.001) while glycolytic potential was reduced (208.0% vs. 286.8%, p < 0.001), corroborated by lower ascitic lactate concentrations (1.9 vs. 3.8 mM/L, p<0.001). Patients with low ascites OXPHOS potential had higher risk of developing SBP (p = 0.016). CD4 ⁺ T cells in ascites showed elevated PD-1 expression (36.9% vs. 14.7%, p < 0.0001), associated with reduced OXPHOS potential (407.1% vs. 324.6% in PD-1-low vs. PD-1-high cells, p = 0.036). Conclusion: Peritoneal immune cells exhibit a dissociated phenotype—elevated oxidative activity alongside features of immune exhaustion—reflecting their distinct role in immune regulation within the peritoneal environment.
SN - 1664-3224
ER -