Pharmacological intervention of the HMGB1-pCTS-L axis to ameliorate inflammatory diseases
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By
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Weiqiang Chen
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Jianhua Li
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Xiaoling Qiang
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Li Lou
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Cassie Shu Zhu
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Meihong Deng
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Haichao Wang
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May 8, 2026
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Clinical Scorecard: Targeting the HMGB1-pCTS-L Pathway for the Treatment of Inflammatory Disorders
At a Glance
| Category | Detail |
|---|
| Condition | Inflammatory Disorders (e.g., Sepsis, Rheumatoid Arthritis) |
| Key Mechanisms | HMGB1 and procathepsin-L (pCTS-L) interactions with TLR4 and RAGE, leading to dysregulated inflammation. |
| Target Population | Patients with acute sepsis and chronic rheumatoid arthritis (RA). |
| Care Setting | Clinical settings managing inflammatory diseases. |
Key Highlights
- HMGB1-pCTS-L axis initiates a sustained inflammatory loop activating non-canonical NF-κB pathway.
- Tetranectin-derived P2–1 peptide inhibits HMGB1-pCTS-L axis without broad immunosuppression.
- Targeting extracellular HMGB1 at pathological sites enhances safety and precision in treatment.
Guideline-Based Recommendations
Diagnosis
- Identify dysregulated inflammation through clinical assessment and biomarkers.
Management
- Consider HMGB1- and pCTS-L-inhibiting antibodies and mimetic peptides for treatment.
Monitoring & Follow-up
- Regularly assess inflammatory markers and patient response to therapy.
Risks
- Monitor for potential adverse effects related to immune modulation.
Patient & Prescribing Data
Individuals with sepsis and rheumatoid arthritis.
Delayed treatment with P2–1 peptide shows efficacy in ameliorating symptoms.
Clinical Best Practices
- Utilize targeted therapies that inhibit specific inflammatory pathways.
- Avoid broad immunosuppressive treatments to minimize adverse effects.
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