2. Academic Validation
  3. IgG antibodies to dengue enhanced for FcγRIIIA binding determine disease severity

IgG antibodies to dengue enhanced for FcγRIIIA binding determine disease severity

  • Science. 2017 Jan 27;355(6323):395-398. doi: 10.1126/science.aai8128.
Taia T Wang 1 2,  Jaturong Sewatanon 3 4 5,  Matthew J Memoli 6,  Jens Wrammert 4 7,  Stylianos Bournazos 1,  Siddhartha Kumar Bhaumik 4 7,  Benjamin A Pinsky 2 8,  Kulkanya Chokephaibulkit 9,  Nattawat Onlamoon 10,  Kovit Pattanapanyasat 10,  Jeffery K Taubenberger 6,  Rafi Ahmed 3 4,  Jeffrey V Ravetch 11
Affiliations

Affiliations

  • 1 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • 2 Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 3 Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 4 Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 5 Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 10700.
  • 6 Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 7 Division of Infectious Disease, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 8 Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 9 Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand 10700.
  • 10 Department of Research and Development, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand 10700.
  • 11 Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. ravetch@rockefeller.edu.
PMID: 28126818 DOI: 10.1126/science.aai8128
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.

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