Abstract
In retrospect, the therapeutic potential of immunoglobulins was first demonstrated by von Behring and Kitasato in the late nineteenth century by protecting mice from the lethal effects caused by tetanus and diphtheria toxin via injection of a hyperimmune serum generated in rabbits. Even today, hyperimmune sera generated from human donors with high serum titers against a certain pathogen are still in use as a means of providing passive protection. More importantly, therapeutic antibodies specific for malignant or autoreactive cells have become included in the standard of care in diseases such as breast cancer and malignant lymphoma. Despite this clinical success, we are only at the beginning of understanding the precise molecular and cellular pathways responsible for immunoglobulin G (IgG) activity in vivo. Since then, an enormous amount of information about the mechanism of IgG activity has been obtained in various model systems. The aim of this review is to provide a comprehensive overview of our current understanding of how IgG antibodies mediate their activity in vivo and how we can use this knowledge to enhance the activity of therapeutic antibodies or block the proinflammatory and tissue pathology inducing activity of autoantibodies.
Highlights
Antibodies of the immunoglobulin G (IgG) isotype are an essential component of our armament against pathogenic microorganisms
The aim of this review is to provide a comprehensive overview of our current understanding of how IgG antibodies mediate their activity in vivo and how we can use this knowledge to enhance the activity of therapeutic antibodies or block the proinflammatory and tissue pathology inducing activity of autoantibodies
Apart from this proinflammatory, cytotoxic, and phagocytic activity of IgG molecules, it has become clear over the recent years that IgG molecules in the form of polyclonal serum IgG preparations pooled from thousands of donors can have an active anti-inflammatory activity, which is used in the clinic to treat autoantibody-mediated autoimmune diseases such as ITP, chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barresyndrome, and more recently skin blistering diseases [6, 7]
Summary
Antibodies of the IgG isotype are an essential component of our armament against pathogenic microorganisms. A detailed understanding of the molecular and cellular mechanisms underlying IgG activity are of great importance as this may allow (1) improving therapeutic antibodies and (2) preventing the proinflammatory activity of autoantibodies allowing the development of novel therapeutic avenues to treat autoimmune disease Apart from this proinflammatory, cytotoxic, and phagocytic activity of IgG molecules, it has become clear over the recent years that IgG molecules in the form of polyclonal serum IgG preparations pooled from thousands of donors (so called intravenous IgG or IVIg therapy) can have an active anti-inflammatory activity, which is used in the clinic to treat autoantibody-mediated autoimmune diseases such as ITP, CIDP, Guillain-Barresyndrome, and more recently skin blistering diseases [6, 7]. Despite not being the major topic of this review, to understand how this paradoxic antiinflammatory works, it is critical to understand which molecular and cellular pathways are responsible for the proinflammatory activity of IgG
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