Simon J Cleary, Yurim Seo, Jennifer J Tian, Nicholas Kwaan, David P Bulkley, Arthur E H Bentlage, Gestur Vidarsson, Éric Boilard, Rolf Spirig, James C Zimring, Mark R Looney
Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful antibodies often activate the complement cascade. A model for how IgG antibodies trigger complement activation involves interactions between IgG Fc domains driving assembly of IgG hexamer structures that activate C1 complexes. The importance of IgG hexamers in initiating injury responses was unclear, so we tested their relevance in a mouse model of alloantibody and complement-mediated acute lung injury...
March 26, 2024: Journal of Clinical Investigation