Intravenous immune globulin suppresses angiogenesis in mice and humans

. 2016 ; 1 () : 15002-. [epub] 20160128

Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, N.I.H., Extramural

Perzistentní odkaz   https://www.medvik.cz/link/pmid26925256

Grantová podpora
R01 EY017182 NEI NIH HHS - United States
R00 EY024336 NEI NIH HHS - United States
R01 EY018350 NEI NIH HHS - United States
K99 EY024336 NEI NIH HHS - United States
UL1 RR033173 NCRR NIH HHS - United States
R01 EY018836 NEI NIH HHS - United States
R01 EY020672 NEI NIH HHS - United States
T32 HL091812 NHLBI NIH HHS - United States
R01 EY024068 NEI NIH HHS - United States
R01 EY017950 NEI NIH HHS - United States
DP1 GM114862 NIGMS NIH HHS - United States
R01 EY022238 NEI NIH HHS - United States

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.

Angiogenesis Lab Institute of Genetics and Biophysics CNR Naples Italy

Angiogenesis Lab Institute of Genetics and Biophysics CNR Naples Italy; Bio Ker MultiMedica Group Naples Italy

Angiogenesis Lab Institute of Genetics and Biophysics CNR Naples Italy; IRCCS MultiMedica Milano Italy

Department of Advanced Biomedical Sciences University of Naples 'Federico II' Naples Italy; CEINGE Biotecnologie Avanzate s c ar l Naples Italy

Department of Human Genetics Leiden University Medical Center Leiden The Netherlands

Department of Nephrology Institute for Clinical and Experimental Medicine Prague 4 Czech Republic

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

Department of Ophthalmology and Visual Sciences University of Kentucky Lexington KY USA

Department of Ophthalmology and Visual Sciences University of Kentucky Lexington KY USA; Angiogenesis Lab Institute of Genetics and Biophysics CNR Naples Italy

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

Department of Ophthalmology and Visual Sciences University of Kentucky Lexington KY USA; Department of Ophthalmology Nagoya University Graduate School of Medicine Nagoya Japan

Department of Ophthalmology and Visual Sciences University of Kentucky Lexington KY USA; Department of Physiology University of Kentucky Lexington KY USA

Immunotherapy Laboratory Laboratory for Translational Immunology University Medical Center Utrecht Utrecht The Netherlands

Rheumatology Unit Department of Medicine Karolinska Institutet Karolinska University Hospital Stockholm Sweden

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