Longevity & AgingNew Humanized Antibody Breaks Sepsis Inflammation Cycle at Its Source
Researchers developed a humanized monoclonal antibody (hCitH3-mAb) targeting citrullinated histone H3 (CitH3), a key driver of sepsis-related inflammation. CitH3 is released during NETosis and activates a damaging feedback loop via TLR2 and PAD2. In mouse models of LPS- and Pseudomonas aeruginosa-induced sepsis, hCitH3-mAb reduced cytokine storms, decreased mortality, lessened acute lung injury, and enhanced bacterial clearance in the lungs, spleen, and liver. The team also identified an optimal therapeutic window using a novel ultrasensitive digital ELISA method, and uncovered the molecular mechanism by which CitH3 sustains its own production through calcium-dependent PAD2 auto-citrullination and nuclear translocation.
