Immunological signatures of sepsis in abdominal solid organ transplant recipients: A multilayer and multicentric prospective cohort study

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.

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Publication Details

Journal
Intensive Care Medicine
Published
2026-10-29
DOI
https://doi.org/10.1007/s00134-026-08612-1
Primary Topic
Sepsis Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

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article

Immunological signatures of sepsis in abdominal solid organ transplant recipients: A multilayer and multicentric prospective cohort study

Birte Dyck, Thilo Bracht, Dietrich Henzler, Matthias Unterberg et al.
2 links
Intensive Care Medicine
Sepsis Diagnosis and Treatment
article

Immunological signatures of sepsis in abdominal solid organ transplant recipients: A multilayer and multicentric prospective cohort study

Birte Dyck, Thilo Bracht, Dietrich Henzler, Matthias Unterberg, Ulrik Stervbo, Christian Hugo, Alexander Zarbock, Tim Rahmel, Jérôme Defosse, Andreas Anton Schnitzbauer, Christian Putensen, Sindy Neumann, Lars Bergmann, Björn Koos, Andrea Witowski, Katharina Rump, Michael Adamzik, Frank Wappler, Barbara Sitek, Patrick Thon, Alexander Wolf, Hartmuth Nowak, Kamil Sebastian Rosiewicz, Dominik Ziehe, Philipp Pagel, Nina Babel, Lena Kröger, Andreas Pascher, Britta Westhus, Stefan Felix Ehrentraut
article en

Abstract

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.

Intensive Care Medicine
Witten/Herdecke University (DE), University Hospital Bonn (DE), University Hospitals of the Ruhr-University of Bochum (DE), Universitätsklinik Marien Hospital Herne (DE), University Hospital Münster (DE), Universitätsklinikum Knappschaftskrankenhaus Bochum (DE), Herford Hospital (DE), University Hospital Carl Gustav Carus (DE), Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE), Ruhr University Bochum (DE)
European Commission, Deutsche Forschungsgemeinschaft, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 12%
Sepsis Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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