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

Summary

In a post hoc analysis of a prospective multicenter cohort, abdominal solid organ transplant recipients with sepsis had higher 30-day survival than non-transplant patients (84% versus 66%; adjusted hazard ratio 0.49). They showed lower IL-6 and TNF-α, higher IL-18, relatively preserved monocytic HLA-DR expression, and distinct innate immune, complement, lipid-metabolic, and cellular immunometabolic signatures. The findings suggest that chronic immunosuppression may reshape rather than simply suppress the septic host response.

Key Findings

• Thirty-day survival was 84% in abdominal solid organ transplant recipients versus 66% in non-transplant patients; adjusted hazard ratio was 0.49.
• Transplant recipients had lower IL-6 and TNF-α, higher IL-18, and relatively preserved monocytic HLA-DR expression.
• Proteomic and intracellular analyses identified distinct innate immune, complement, lipid-metabolic, GLUT1, and TFAM/TFB2M-associated signatures.

Clinical Implications

Transplant status should not be interpreted as an automatic marker of poor prognosis in sepsis. Immune profiling, particularly monocytic HLA-DR, cytokine patterns, and immunometabolic markers, may eventually support individualized monitoring and treatment, although these markers are not yet validated for routine therapeutic decisions.

Limitations

• The transplant analysis was post hoc and observational, so residual confounding and selection bias cannot be excluded.
• Immune and immunometabolic markers were not prospectively tested to guide treatment allocation.

Future Directions

Prospective studies should validate whether the identified immune signatures predict treatment response and whether transplant-specific phenotypes can guide immunomodulatory or organ-support strategies.