Chapter 15 : Dengue Antibody-Dependent Enhancement: Knowns and Unknowns

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Antibody-dependent enhancement (ADE) is a phenomenon involving infectious IgG antibody immune complexes that mediate the worsening of diseases involving a wide spectrum of microbes and vertebrates. ADE is a new type of Gell-Coombs immunopathology: type I, IgE-mediated immediate hypersensitivity; type II, antibody-mediated acute immune complex disease; type III, IgG-mediated complement-dependent foreign antigen immune complex disease; type IV, cell-mediated immune and autoimmune diseases; and type V, IgG immune complex enhancement of microbial infection in Fc-receptor (FcR)-bearing cells. Three of these immunopathologies are mediated by IgG antibodies. Type V immunopathology differs in function from type II and III immunopathologies in that immune complexes are not directly cytotoxic but serve to increase disease severity by regulating the productivity of intracellular microbial infection. In type II immunopathologies, IgG antibodies are often directed at autoantigens and include acute rheumatic fever where microbial antigens mimic antigens in various human tissues, generating an immune response that breaks down immune tolerance. In type III immunopathologies foreign antigen-antibody complexes are often trapped in the basement membranes of endothelial linings. Examples include acute serum sickness, glomerular nephritis, and postimmunization diseases such as breakthrough measles and respiratory syncytial virus infections in vaccine recipients that result in destructive complement-fixing virus-IgG immune complexes predominantly in the lung ( ).

Citation: Halstead S. 2015. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns, p 249-271. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0022-2014
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Dengue vascular permeability syndrome

Citation: Halstead S. 2015. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns, p 249-271. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0022-2014
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Context for understanding “known” and studying “unknown” factors that contribute to the pathogenesis of the dengue vascular permeability syndrome via ADE

Citation: Halstead S. 2015. Dengue Antibody-Dependent Enhancement: Knowns and Unknowns, p 249-271. In Crowe J, Boraschi D, Rappuoli R (ed), Antibodies for Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.AID-0022-2014

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