Immunological signatures of sepsis in abdominal solid organ transplant recipients: A multilayer and multicentric prospective cohort study
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Updated: Oct 31, 2026
Investigating the Immunological Mechanisms Underlying Organ Transplant Rejection
Published on: August 20, 2007
Andrea Witowski1,2, Thilo Bracht3,4, Lena Kröger5
1Ruhr University Bochum, Knappschaft Kliniken University Hospital Bochum, Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Bochum, Germany. andrea.witowski@ruhr-uni-bochum.de.
Background:
Sepsis is defined as life-threatening organ dysfunction resulting from a dysregulated host response to infection. Patients with prior abdominal solid organ transplantation (SOT) are highly susceptible to infection due to chronic immunosuppression, yet exhibit improved survival once sepsis occurs. The underlying mechanisms remain poorly understood.
Methods:
We conducted a post hoc analysis within a prospective multicenter cohort of septic patients (SepsisDataNet.NRW; n = 538). Clinical outcomes were assessed using Kaplan-Meier analysis and multivariable Cox regression. Immune profiling included serum cytokines, flow cytometric immunophenotyping, plasma proteomics, and intracellular signaling using proximity ligation assays (PLA) in peripheral blood mononuclear cells (PBMCs). To reduce clinical confounding, complementary exploratory analyses were performed in a non-septic kidney transplant cohort (e:KID).
Results:
SOT patients demonstrated improved 30-day survival compared with non-SOT patients (84% vs. 66%; adjusted HR 0.49, 95% CI 0.26-0.95). Cytokine analysis revealed lower IL-6 and TNF-α levels alongside higher IL-18 concentrations, indicating an altered inflammatory profile. Flow cytometry showed reductions in adaptive immune cells but relatively preserved innate immune function, reflected by higher monocytic HLA-DR expression. Proteomics identified enrichment of innate immune, complement, and lipid metabolic response networks. PLA-based cellular analyses revealed increased GLUT1 expression and enhanced TFAM/TFB2M interaction in SOT patients, indicating a distinct immunometabolic marker profile. In e:KID patients paired serum metabolomics demonstrated higher glucose and lower lactate concentrations 12 months after transplantation, accompanied by broader alterations in lipid and branched-chain amino acid profiles.
Conclusion:
In patients with sepsis, abdominal SOT is associated with significant better survival than in non-SOT patients. Septic abdominal SOT patients display a distinct immune phenotype characterized by attenuated systemic inflammation, relative preservation of selected innate immune readouts, and alterations in immunometabolic markers.
