{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Chen W"],"funding":["NCCIH NIH HHS","NIGMS NIH HHS"],"pubmed_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"],"journal":["Research square"],"pagination":["rs.3.rs-7633404"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12458545"],"repository":["biostudies-literature"],"pubmed_title":["Repurposing a Detrimental Antibody Epitope as Targeted Therapeutics for Sepsis and Rheumatoid Arthritis."],"pmcid":["PMC12458545"],"funding_grant_id":["R01 AT005076","R35 GM145331"],"pubmed_authors":["Yang H","Li J","Wang P","Tracey KJ","Chen W","Xiong B","Qiang X","Zhu CS","Wang H","Chen S","Lou L"],"additional_accession":[]},"is_claimable":false,"name":"Repurposing a Detrimental Antibody Epitope as Targeted Therapeutics for Sepsis and Rheumatoid Arthritis.","description":"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","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-04T03:16:52.795Z","creation":"2026-06-04T03:06:36.734Z"},"accession":"S-EPMC12458545","cross_references":{"pubmed":["41001546"],"doi":["10.21203/rs.3.rs-7633404/v1"]}}