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Antibody-Dependent Enhancement (ADE) and the role of complement system in disease pathogenesis

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journal contribution
submitted on 2023-11-07, 07:12 and posted on 2023-11-07, 12:37 authored by Swapna Thomas, Maria K. Smatti, Allal Ouhtit, Farhan S. Cyprian, Muna A. Almaslamani, Asmaa Al Thani, Hadi M. Yassine

Antibody-dependent enhancement (ADE) has been associated with severe disease outcomes in several viral infections, including respiratory infections. In vitro and in vivo studies showed that antibody-response to SARS-CoV and MERS-CoV could exacerbate infection via ADE. Recently in SARS CoV-2, the in vitro studies and structural analysis shows a risk of disease severity via ADE. This phenomenon is partially attributed to non-neutralizing antibodies or antibodies at sub-neutralizing levels. These antibodies result in antigen-antibody complexes' deposition and propagation of a chronic inflammatory process that destroys affected tissues. Further, antigen-antibody complexes may enhance the internalization of the virus into cells through the Fc gamma receptor (FcγR) and lead to further virus replication. Thus, ADE occur via two mechanisms; 1. Antibody mediated replication and 2. Enhanced immune activation. Antibody-mediated effector functions are mainly driven by complement activation, and the first complement in the cascade is complement 1q (C1q) which binds to the virus-antibody complex. Reports say that deficiency in circulating plasma levels of C1q, an independent predictor of mortality in high-risk patients, including diabetes, is associated with severe viral infections. Complement mediated ADE is reported in several viral infections such as dengue, West Nile virus, measles, RSV, Human immunodeficiency virus (HIV), and Ebola virus. This review discusses ADE in viral infections and the in vitro evidence of ADE in coronaviruses. We outline the mechanisms of ADE, emphasizing the role of complements, especially C1q in the outcome of the enhanced disease.

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Published in: Molecular Immunology
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Open Access funding provided by the Qatar National Library



  • English



Publication Year

  • 2022

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This Item is licensed under the Creative Commons Attribution 4.0 International License

Institution affiliated with

  • Qatar University
  • Biomedical Research Center - QU
  • College of Arts and Sciences - QU
  • Qatar University Health - QU
  • College of Health Sciences - QU HEALTH
  • College of Medicine - QU HEALTH
  • Hamad Medical Corporation
  • Communicable Disease Center - HMC