ImmunoTargets and Therapy (Oct 2020)
Time to Develop Therapeutic Antibodies Against Harmless Proteins Colluding with Sepsis Mediators?
Abstract
Jianhua Li,1,* Guoqiang Bao,2,* Haichao Wang1,3 1The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USA; 2Department of General Surgery, Tangdu Hospital, Xi’an, Shaanxi 710032, People’s Republic of China; 3Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA*These authors contributed equally to this workCorrespondence: Haichao Wang Tel +1 516 562-2823Email [email protected]: Sepsis refers to a systemic inflammatory response syndrome resulting from microbial infections, and is partly attributable to dysregulated inflammation and associated immunosuppression. A ubiquitous nuclear protein, HMGB1, is secreted by activated leukocytes to orchestrate inflammatory responses during early stages of sepsis. When it is released by injured somatic cells at overwhelmingly higher quantities, HMGB1 may induce macrophage pyroptosis and immunosuppression, thereby impairing the host’s ability to eradicate microbial infections. A number of endogenous proteins have been shown to bind HMGB1 to modulate its extracellular functions. Here, we discuss an emerging possibility to develop therapeutic antibodies against harmless proteins that collude with pathogenic mediators for the clinical management of human sepsis and other inflammatory diseases.Keywords: antibody, HMGB1, immunosuppression, inflammation, innate immune cells, pyroptosis, sepsis
