| Literature DB >> 28126818 |
Taia T Wang1,2, Jaturong Sewatanon3,4,5, Matthew J Memoli6, Jens Wrammert4,7, Stylianos Bournazos1, Siddhartha Kumar Bhaumik4,7, Benjamin A Pinsky2,8, Kulkanya Chokephaibulkit9, Nattawat Onlamoon10, Kovit Pattanapanyasat10, Jeffery K Taubenberger6, Rafi Ahmed3,4, Jeffrey V Ravetch11.
Abstract
Dengue virus (DENV) infection in the presence of reactive, non-neutralizing immunoglobulin G (IgG) (RNNIg) is the greatest risk factor for dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Progression to DHF/DSS is attributed to antibody-dependent enhancement (ADE); however, because only a fraction of infections occurring in the presence of RNNIg advance to DHF/DSS, the presence of RNNIg alone cannot account for disease severity. We discovered that DHF/DSS patients respond to infection by producing IgGs with enhanced affinity for the activating Fc receptor FcγRIIIA due to afucosylated Fc glycans and IgG1 subclass. RNNIg enriched for afucosylated IgG1 triggered platelet reduction in vivo and was a significant risk factor for thrombocytopenia. Thus, therapeutics and vaccines restricting production of afucosylated, IgG1 RNNIg during infection may prevent ADE of DENV disease.Entities:
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Year: 2017 PMID： 28126818 PMCID： PMC5557095 DOI： 10.1126/science.aai8128
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728