Dynamic sepsis endotypes: instability or expected signal of biological progression? Author's reply - Summary - MDSpire

Dynamic sepsis endotypes: instability or expected signal of biological progression? Author's reply

  • By

  • Emma Rademaker

  • Harm-Jan de Grooth

  • Olaf L. Cremer

  • February 17, 2026

  • 0 min

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Objective:

To address the argument that immune profile transitions in sepsis patients reflect biological evolution rather than classification error, emphasizing the implications for clinical practice.

Key Findings:
  • Observed transition rates of immune profiles were 41%, 39%, and 22%, significantly higher than the expected biological variation of 15-25%, indicating potential classification error.
  • Rapid transitions within 8-hour intervals suggest classification error rather than true biological change, raising concerns for therapy selection.
  • Patients near profile boundaries experienced unstable assignments, indicating a higher likelihood of random reassignment, which complicates targeted therapy.
Interpretation:

The high transition rates and instability of immune profile assignments challenge the reliability of immunological profiling for guiding targeted therapies in sepsis, suggesting a need for reevaluation of current practices.

Limitations:
  • The study's findings may not apply to different clinical settings, such as emergency departments, where faster class changes were observed, potentially skewing results.
  • The reliance on serial immunological measurements may limit generalizability, as different settings may yield different transition dynamics.
Conclusion:

Substantial classification instability over short timescales undermines the clinical utility of proposed immune endotypes for therapy selection in sepsis, necessitating a reconsideration of how these profiles are used in practice.

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