Daily Sepsis Research Analysis
A proteome-wide atlas now infers the organ origin of plasma proteins and demonstrates disease-specific signatures in sepsis, enabling precision phenotyping. Mechanistic work identifies TREM2-driven inflammatory CD11c+ B cells that worsen sepsis outcomes. A translational study proposes METRNL as a rapidly released, endothelium-derived biomarker with diagnostic performance comparable to procalcitonin.
Summary
A proteome-wide atlas now infers the organ origin of plasma proteins and demonstrates disease-specific signatures in sepsis, enabling precision phenotyping. Mechanistic work identifies TREM2-driven inflammatory CD11c+ B cells that worsen sepsis outcomes. A translational study proposes METRNL as a rapidly released, endothelium-derived biomarker with diagnostic performance comparable to procalcitonin.
Research Themes
- Organ-origin plasma proteomics for precision sepsis phenotyping
- B-cell mediated immune dysregulation via TREM2 in sepsis
- Early endothelial biomarkers for sepsis diagnosis
Selected Articles
1. Human proteome distribution atlas for tissue-specific plasma proteome dynamics.
This study constructs a mass spectrometry-based atlas linking plasma proteins to their tissue of origin across 18 organs and major blood cell types, integrated with RNA/protein resources. The approach detects organ-enriched protein changes in six patient cohorts, including sepsis, providing a scalable framework for precision diagnostics and pathophysiology.
Impact: Provides a foundational resource and method to trace organ-specific protein signals in plasma, directly applicable to sepsis phenotyping and organ injury assessment.
Clinical Implications: Enables development of organ-specific plasma panels to differentiate sepsis endotypes and track organ injury (e.g., liver, kidney, endothelium), potentially informing targeted therapies and monitoring.
Key Findings
- Built a proteome atlas from 18 vascularized organs and 8 abundant blood cell types
- Integrated with RNA/protein atlases to define proteome-wide organ associations and infer tissue origin of plasma proteins
- Demonstrated disease-specific quantitative changes of organ-enriched protein panels in six patient cohorts, including sepsis
- Provides a reproducible, extensible strategy for plasma proteome dynamics in health and disease
Methodological Strengths
- Mass-spectrometry-based profiling across 18 organs and multiple blood cell types
- Cross-resource integration with transcriptomic/proteomic atlases and validation in six clinical cohorts
Limitations
- Abstract does not detail cohort sample sizes or clinical endpoints for sepsis
- Resource study; not a prospective diagnostic or interventional trial
Future Directions: Prospective validation of organ-specific panels for sepsis endotyping, integration with clinical decision tools, and testing utility for guiding organ-targeted therapies.
2. Inflammatory CD11c+ B Cells Induced by the TREM2 Signal Accelerate Sepsis Development.
The authors identify a proinflammatory CD11c+ B-cell subset that expands in sepsis and, upon adoptive transfer, exacerbates sepsis-induced lung injury and mortality in mice. Mechanistically, TREM2 signaling drives their generation via IRF4, positioning a TREM2–CD11c+ B-cell axis as a driver of inflammatory injury.
Impact: Reveals a previously underappreciated B-cell axis in sepsis pathogenesis and nominates TREM2 as a potential therapeutic target.
Clinical Implications: Targeting the TREM2–CD11c+ B-cell axis could mitigate inflammatory organ injury in sepsis; the subset may also serve as a biomarker of a hyperinflammatory endotype.
Key Findings
- Identified a proinflammatory CD11c+ B-cell subset expanded in septic patients and mouse models
- Adoptive transfer of CD11c+ B cells accelerated sepsis-induced lung injury and increased mortality in mice
- TREM2 signaling induced CD11c+ B cells via the IRF4 pathway
- TREM2 directly contributes to CD11c+ B-cell–mediated inflammatory regulation in sepsis
Methodological Strengths
- Human patient data combined with mechanistic mouse models and adoptive transfer experiments
- Pathway dissection implicating TREM2–IRF4 signaling in CD11c+ B-cell induction
Limitations
- Human cohort size and clinical covariates are not detailed in the abstract
- Therapeutic blockade of TREM2 or CD11c+ B-cell depletion was not tested in patients
Future Directions: Validate CD11c+ B-cell signatures in larger, phenotyped sepsis cohorts and test pharmacologic modulation of TREM2 signaling.
3. Exploring METRNL as a novel biomarker in sepsis: diagnostic potential and secretion mechanism.
METRNL rises rapidly in experimental sepsis (within 1 hour) and is significantly elevated in ICU sepsis patients versus controls, with ROC AUC 0.943 comparable to procalcitonin and higher specificity at the optimal cutoff. Endothelial cells are the main source, with TLR4–ERK signaling mediating rapid secretion via the classical ER–Golgi pathway.
Impact: Introduces a fast, endothelium-derived biomarker with strong diagnostic performance and clear mechanistic underpinning, addressing a key gap in early sepsis detection.
Clinical Implications: METRNL could enable earlier sepsis recognition than PCT/CRP and help identify an endothelial injury phenotype, informing triage, monitoring, and biomarker-guided trials.
Key Findings
- In LPS and CLP models, serum METRNL increased in a dose- and time-dependent manner and within 1 hour, preceding PCT and CRP
- ICU sepsis patients (n=107) had significantly higher METRNL than controls (n=95); ROC AUC 0.943, comparable to PCT (0.955) and superior specificity at optimal cutoff
- Endothelial-specific Metrnl knockout and signaling studies showed endothelium as the main source and TLR4–ERK–ER/Golgi pathway mediating rapid secretion
Methodological Strengths
- Cross-species validation: cell systems, mouse CLP/LPS models, and human ICU cohort
- Mechanistic dissection using endothelial cell–specific knockout and signaling pathway interrogation
Limitations
- Single-center pilot with moderate sample size; external validation needed
- Diagnostic performance not evaluated in prospective emergency triage workflows
Future Directions: Prospective, multicenter diagnostic studies comparing METRNL with PCT/CRP and integration into multi-marker panels for endothelial sepsis endotypes.