Research ArticleSepsis

Identification of tetranectin-targeting monoclonal antibodies to treat potentially lethal sepsis

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Science Translational Medicine  15 Apr 2020:
Vol. 12, Issue 539, eaaz3833
DOI: 10.1126/scitranslmed.aaz3833

Got to keep them separated

Sepsis, potentially lethal organ dysfunction caused by infection, remains a major problem. By investigating the mechanisms of inflammation in sepsis, Chen et al. determined that an antibody blocking the interaction between two proteins may provide a useful intervention. One of these proteins, tetranectin, is depleted in patients with sepsis and associated with better survival in mouse models. The other protein, HMGB1, is a known mediator of sepsis. The authors found that HMGB1 binds tetranectin, resulting in endocytosis of both proteins and worsening inflammation, whereas an antibody blocking this interaction can be protective. A related Focus by Paterson et al. discusses the implications of these findings.

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