Intravenous immune globulin suppresses angiogenesis in mice and humans

Reo Yasuma, Valeria Cicatiello, Takeshi Mizutani, Laura Tudisco, Younghee Kim, Valeria Tarallo, Sasha Bogdanovich, Yoshio Hirano, Nagaraj Kerur, Shengjian Li, Tetsuhiro Yasuma, Benjamin J. Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Balamurali K. Ambati, Sevim Barbasso Helmers, Ingrid E. Lundberg, Ondrej ViklickyJeanette H.W. Leusen, J. Sjef Verbeek, Bradley D. Gelfand, Ana Bastos-Carvalho, Sandro De Falco, Jayakrishna Ambati

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~ 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels.

Original languageEnglish
Article number15002
JournalSignal Transduction and Targeted Therapy
Volume1
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 West China Hospital, Sichuan University.

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

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