Repurposing a Detrimental Antibody Epitope as Targeted Therapeutics for Sepsis and Rheumatoid Arthritis.

ABSTRACT: Sepsis and rheumatoid arthritis (RA) are distinct yet mechanistically related conditions commonly driven by dysregulated inflammatory responses. Here, we explored the counterintuitive hypothesis that an epitope from a deleterious anti-tetranectin (TN) antibody (mAb9) could hold unforeseen therapeutic potential. By mapping mAb9's epitope to P2 (residue 55-70), a region crucial for TN's protective functions, we developed P2-1, a water-soluble derivative as a targeted therapy. P2-1 significantly improved survival and reduced systemic inflammation in a sepsis model, and attenuated arthritis severity and pain sensitivity in a RA model, even with therapeutic administration after disease onset. Mechanistically, P2-1 exhibited high-affinity binding to high mobility group box 1 (HMGB1) and selectiv

SUBMITTER: Chen W 

PROVIDER: S-EPMC12458545 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature