The Institut Pasteur du Cambodge is pleased to share the publication of the paper below published in Science, the peer-reviewed academic journal of the American Association for the Advancement of Science (AAAS). This research on dengue is the result of a collaboration between the Immunology, Epidemiology and Public Health and Virology teams at Institut Pasteur du Cambodge (T. Cantaert), Rockefeller University, USA (J. Ravetch) and a team at Institut Pasteur, Paris (A. Sakuntabhai).
“Antibody fucosylation predicts disease severity in secondary dengue infection”
Dengue disease can develop after a bite from a dengue-virus infected mosquito. The clinical outcome after the mosquito bite are variable. Some individuals do not develop symptoms and other individuals develop life-threatening disease with associated thrombocytopenia and hemorrhagic disease. Secondary heterotypic infection is the greatest risk factor to develop severe disease, when pre-existing DENV-reactive antibodies promote the infection of immune cells. However, additional susceptibility factors exist, as less than 5% of patients with pre-existing DENV-reactive antibodies develop severe disease.
We have studied the Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. We could show that IgG1 afucosylation level is associated to disease outcome after infection, as inapparent cases had lower abundance of afucosylated antibodies compared to hospitalized patients. Moreover, IgG1 afucosylation is associated with dengue disease severity and correlates with biological features of severe disease at hospital admission. Analyzing plasma samples from individuals before and after infection revealed that afucosylation increases after infection and during convalescence.
In conclusion, we found that DENV infection induced specific increases in IgG1 afucosylation and levels of afucosylated IgG1 could indeed predict dengue disease severity, making IgG1 afucosylation status a potentially useful prognostic tool for the treatment of dengue patients. Our studies highlight a key role of the Fc glycan structure in dengue pathogenesis.