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Mechanisms of Action and Immunomodulation by IVIg

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Antibody Therapy

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Abstract

Intravenous immunoglobulin (IVIg) has been e1ectively used as a replacement product for those deficient in IgG as well as for treating a number of autoimmune syndromes. Although the precise mechanism of action of IVIg as an immunomodulatory agent has been elusive, many theories over the years have been postulated. These theories include mononuclear phagocytic system blockade, autoantibody neutralization, increased clearance of pathogenic autoantibodies through the neonatal Fc receptor (FcRn), complement neutralization, modulation of inflammatory and/or anti-inflammatory cytokines, programmed cell death, anti-inflammatory effects mediated through the inhibitory Fc receptor (FcγRIIB), activating Fc receptor-dependent dendritic cell modulation, induction of T regulatory cells and other mechanisms. Some of the key attributes of IVIg which could contribute to some of these mechanisms have included effects mediated through the Fab region of IgG, while others have been through the Fc region of IVIg. The presence of sugars or glycans on the Fc region have been considered by some to be important, while other work has pointed to a major role for IgG dimers or immune complexes as mediating IVIg anti-inflammatory activity. This review will discuss our current understanding of the mechanism of action of IVIg on its immunomodulatory properties in autoimmunity with an emphasis from work performed using murine models of immune thrombocytopenia (ITP). Finally, we will discuss some recent advances in recombinant IVIg alternatives.

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Authors and Affiliations

  1. Centre for Innovation at The Canadian Blood Services, Ottawa, ON, Canada

    Alan H. Lazarus PhD

  2. Keenan Research Centre of the Li Ka Shing Knowledge Institute at St. Michael’s Hospital, Toronto, ON, Canada

    Alan H. Lazarus PhD

  3. Departments of Medicine and Laboratory Medicine & Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Alan H. Lazarus PhD

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  1. Alan H. Lazarus PhD
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Correspondence to Alan H. Lazarus PhD .

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  1. Department of Pediatrics, Medical Faculty of the University of Basel, Basel, Switzerland

    Paul Imbach

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Lazarus, A.H. (2018). Mechanisms of Action and Immunomodulation by IVIg. In: Imbach, P. (eds) Antibody Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-68038-5_6

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  • DOI: https://doi.org/10.1007/978-3-319-68038-5_6

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-68037-8

  • Online ISBN: 978-3-319-68038-5

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