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SCIRC Scientists Contribute to Landmark Consensus Framework to Advance Precision Immunology in Sepsis and Critical Illness

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SCIRC Scientists Contribute to Landmark Consensus Framework to Advance Precision Immunology in Sepsis and Critical Illness

Gainesville, FL — September 30, 2025 — Researchers affiliated with the University of Florida’s Sepsis & Critical Illness Research Center (SCIRC) are proud to announce their participation in the publication of a major new paper in Nature Medicine, titled “A consensus immune dysregulation framework for sepsis and critical illnesses.” (nature.com)

This paper, published on September 30, 2025, consolidates multiple prior transcriptomic “endotyping” approaches in sepsis and related critical illnesses, harmonizing them into a unified, cell lineage-aware framework. The new “Hi-DEF” (Human Immune Dysregulation Evaluation Framework) quantifies immune dysregulation along both myeloid and lymphoid axes, and demonstrates associations with disease severity, outcomes, and differential responses to immunomodulatory therapies.

Key Findings & Implications

  • By assembling and analyzing >7,000 samples across 37 independent cohorts, the authors found that disparate previously published endotyping schemes converge intofour consensus molecular clusters (endotypes), which map to immune dysregulation along myeloid and lymphoid dimensions.
  • The Hi-DEF scores (myeloid dysregulation, lymphoid dysregulation) correlate strongly with patient severity and 30-day mortality across multiple public and consortium (“SUBSPACE”) datasets.
  • Importantly, Hi-DEF shows generalizability beyond sepsis into other critical illness syndromes (trauma, burns, ARDS) and in immunocompromised populations, suggesting a shared biologic basis of systemic inflammation.
  • In retrospective analyses of randomized trials (e.g. SAVE-MORE, VICTAS, VANISH), the authors observed that lymphoid dysregulation at baseline was associated with preferential benefit from therapies such as anakinra or steroids in certain subgroups—highlighting the potential for precision immunomodulation.

SCIRC’s Role & Future Directions

Members of SCIRC, including UF investigators and collaborators, contributed data, analysis, and domain expertise to the SUBSPACE consortium, which underlies this integrative work. SCIRC is a national leader in sepsis and post-sepsis biology, with leading projects in immune endotypes, long-term outcomes, and translational science.

“This framework gives us a common way to describe and measure immune changes in critically ill patients,” said Dr. Philip Efron, SCIRC Director, “It moves us closer to more personalized treatments for sepsis, helping us understand which patients may benefit most from certain therapies.”

Going forward, SCIRC aims to:

  • Validate Hi-DEF prospectively in UF’s critical care patient populations and biobanked samples
  • Develop computational pipelines and assays for rapid scoring of immune dysregulation in the ICU
  • Partner in clinical trial design to test immunomodulatory therapies targeted to specific dysregulation phenotypes
  • Extend the framework into multi-omics (proteomic, single-cell) and mechanistic studies

“This study reflects years of progress in sepsis research and the power of global collaboration,” said Dr. Lyle Moldawer, Professor Emeritus of Surgery at the University of Florida. “By bringing together data from across institutions, we now have a framework that not only advances precision medicine in critical care but also lays the groundwork for future therapies tailored to individual patients.”

About SCIRC

The Sepsis & Critical Illness Research Center (SCIRC) at the University of Florida is the nation’s first center dedicated to understanding, diagnosing, and treating sepsis and its long-term consequences. Located in Gainesville, the center brings together multidisciplinary teams spanning immunology, critical care, bioinformatics, clinical trials, and translational research. (scirc.med.ufl.edu)

SCIRC’s mission is to develop new solutions for sepsis and its downstream effects, and to push boundaries of knowledge toward improved patient outcomes.

For more information about the SCIRC, please contact Amanda Reifenrath, Program Manager at Amanda.Reifenrath@surgery.ufl.edu.Fig 4