Patients re-infected with dengue virus of a serotype different from that of the initial infection are thought to be at risk of developing severe dengue hemorrhagic fever, due to the production of non-neutralizing antibodies to the second dengue virus. In Science, Ravetch and colleagues report alterations in the glycosylation pattern of anti-viral immunoglobulin G1 (IgG1) in those patients who develop severe disease after re-infection relative to the pattern in other patients who experience a milder disease. Loss of IgG1 fucosylation and increased ratios of IgG1 to IgG2 correlate with the platelet loss (thrombocytopenia) that characterizes severe dengue disease. 'Humanized' mice receiving patients' afucosylated IgG1, which binds with higher affinity to activating FcγRIII receptors than does fucosylated IgG1, experienced FcγR-dependent platelet loss. Furthermore, IgG1 that recognizes dengue NS1 protein cross-reacts with platelet proteins. Thus, disease severity is linked to cross-reactive IgG1 with afucosylated Fc regions that recognize FcgRIII with great avidity.

Science 355, 395–398 (2017)