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Yasuma R, Cicatiello V, Mizutani T, et al. Intravenous immune globulin suppresses angiogenesis in mice and humans. Signal Transduct Target Ther. 2016;1doi: 10.1038/sigtrans.2015.2.
Yasuma, R., Cicatiello, V., Mizutani, T., Tudisco, L., Kim, Y., Tarallo, V., Bogdanovich, S., Hirano, Y., Kerur, N., Li, S., Yasuma, T., Fowler, B. J., Wright, C. B., Apicella, I., Greco, A., Brunetti, A., Ambati, B. K., Helmers, S. B., Lundberg, I. E., Viklicky, O., Leusen, J. H., Verbeek, J. S., Gelfand, B. D., Bastos-Carvalho, A., De Falco, S., & Ambati, J. (2016). Intravenous immune globulin suppresses angiogenesis in mice and humans. Signal transduction and targeted therapy, 1. https://doi.org/10.1038/sigtrans.2015.2
Yasuma, Reo, et al. "Intravenous immune globulin suppresses angiogenesis in mice and humans." Signal transduction and targeted therapy vol. 1 (2016). doi: https://doi.org/10.1038/sigtrans.2015.2
Yasuma R, Cicatiello V, Mizutani T, Tudisco L, Kim Y, Tarallo V, Bogdanovich S, Hirano Y, Kerur N, Li S, Yasuma T, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ambati BK, Helmers SB, Lundberg IE, Viklicky O, Leusen JH, Verbeek JS, Gelfand BD, Bastos-Carvalho A, De Falco S, Ambati J. Intravenous immune globulin suppresses angiogenesis in mice and humans. Signal Transduct Target Ther. 2016;1. doi: 10.1038/sigtrans.2015.2. Epub 2016 Jan 28. PMID: 26925256; PMCID: PMC4768485.
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Signal Transduct Target Ther. 2016;1. doi: 10.1038/sigtrans.2015.2. Epub 2016 Jan 28.

Intravenous immune globulin suppresses angiogenesis in mice and humans.

Signal transduction and targeted therapy

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 Viklicky, Jeanette Hw Leusen, J Sjef Verbeek, Bradley D Gelfand, Ana Bastos-Carvalho, Sandro De Falco, Jayakrishna Ambati

Affiliations

  1. Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  2. Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy; Bio-Ker, MultiMedica Group, Naples, Italy.
  3. Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA.
  4. Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy.
  5. Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy.
  6. Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Physiology, University of Kentucky, Lexington, KY, USA.
  7. Department of Advanced Biomedical Sciences, University of Naples 'Federico II', Naples, Italy; CEINGE-Biotecnologie Avanzate, s.c. ar.l., Naples, Italy.
  8. Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA; Department of Ophthalmology, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA.
  9. Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  10. Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague 4, Czech Republic.
  11. Immunotherapy Laboratory, Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
  12. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
  13. Department of Ophthalmology and Visual Sciences, University of Kentucky, Lexington, KY, USA; Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, USA.
  14. Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy; IRCCS MultiMedica, Milano, Italy.

PMID: 26925256 PMCID: PMC4768485 DOI: 10.1038/sigtrans.2015.2

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.

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