PMID- 26925256
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20210203
LR  - 20220408
IS  - 2095-9907 (Print)
IS  - 2059-3635 (Electronic)
IS  - 2059-3635 (Linking)
VI  - 1
DP  - 2016
TI  - Intravenous immune globulin suppresses angiogenesis in mice and humans.
PG  - 15002-
LID - 15002 [pii]
AB  - 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 FcgammaRI, 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 
      FcgammaRI and had similar potency in transgenic mice expressing human FcgammaRs. 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.
FAU - Yasuma, Reo
AU  - Yasuma R
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA; Department of Ophthalmology, Nagoya University Graduate 
      School of Medicine, Nagoya, Japan.
FAU - Cicatiello, Valeria
AU  - Cicatiello V
AD  - Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy; 
      Bio-Ker, MultiMedica Group, Naples, Italy.
FAU - Mizutani, Takeshi
AU  - Mizutani T
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Tudisco, Laura
AU  - Tudisco L
AD  - Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy.
FAU - Kim, Younghee
AU  - Kim Y
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Tarallo, Valeria
AU  - Tarallo V
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA; Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, 
      Naples, Italy.
FAU - Bogdanovich, Sasha
AU  - Bogdanovich S
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Hirano, Yoshio
AU  - Hirano Y
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Kerur, Nagaraj
AU  - Kerur N
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Li, Shengjian
AU  - Li S
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Yasuma, Tetsuhiro
AU  - Yasuma T
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Fowler, Benjamin J
AU  - Fowler BJ
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA; Department of Physiology, University of Kentucky, Lexington, 
      KY, USA.
FAU - Wright, Charles B
AU  - Wright CB
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - Apicella, Ivana
AU  - Apicella I
AD  - Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy.
FAU - Greco, Adelaide
AU  - Greco A
AD  - Department of Advanced Biomedical Sciences, University of Naples 'Federico II', 
      Naples, Italy; CEINGE-Biotecnologie Avanzate, s.c. ar.l., Naples, Italy.
FAU - Brunetti, Arturo
AU  - Brunetti A
AD  - Department of Advanced Biomedical Sciences, University of Naples 'Federico II', 
      Naples, Italy; CEINGE-Biotecnologie Avanzate, s.c. ar.l., Naples, Italy.
FAU - Ambati, Balamurali K
AU  - Ambati BK
AD  - 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.
FAU - Helmers, Sevim Barbasso
AU  - Helmers SB
AD  - Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska 
      University Hospital, Stockholm, Sweden.
FAU - Lundberg, Ingrid E
AU  - Lundberg IE
AD  - Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska 
      University Hospital, Stockholm, Sweden.
FAU - Viklicky, Ondrej
AU  - Viklicky O
AD  - Department of Nephrology, Institute for Clinical and Experimental Medicine, 
      Prague 4, Czech Republic.
FAU - Leusen, Jeanette Hw
AU  - Leusen JH
AD  - Immunotherapy Laboratory, Laboratory for Translational Immunology, University 
      Medical Center Utrecht, Utrecht, The Netherlands.
FAU - Verbeek, J Sjef
AU  - Verbeek JS
AD  - Department of Human Genetics, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Gelfand, Bradley D
AU  - Gelfand BD
AD  - 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.
FAU - Bastos-Carvalho, Ana
AU  - Bastos-Carvalho A
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA.
FAU - De Falco, Sandro
AU  - De Falco S
AD  - Angiogenesis Lab, Institute of Genetics and Biophysics-CNR, Naples, Italy; IRCCS 
      MultiMedica, Milano, Italy.
FAU - Ambati, Jayakrishna
AU  - Ambati J
AD  - Department of Ophthalmology and Visual Sciences, University of Kentucky, 
      Lexington, KY, USA; Department of Physiology, University of Kentucky, Lexington, 
      KY, USA.
LA  - eng
GR  - R01 EY017182/EY/NEI NIH HHS/United States
GR  - R00 EY024336/EY/NEI NIH HHS/United States
GR  - R01 EY018350/EY/NEI NIH HHS/United States
GR  - K99 EY024336/EY/NEI NIH HHS/United States
GR  - UL1 RR033173/RR/NCRR NIH HHS/United States
GR  - R01 EY018836/EY/NEI NIH HHS/United States
GR  - R01 EY020672/EY/NEI NIH HHS/United States
GR  - T32 HL091812/HL/NHLBI NIH HHS/United States
GR  - R01 EY024068/EY/NEI NIH HHS/United States
GR  - R01 EY017950/EY/NEI NIH HHS/United States
GR  - DP1 GM114862/GM/NIGMS NIH HHS/United States
GR  - R01 EY022238/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160128
PL  - England
TA  - Signal Transduct Target Ther
JT  - Signal transduction and targeted therapy
JID - 101676423
PMC - PMC4768485
MID - NIHMS756665
COIS- JA is a co-founder of iVeena Holdings, iVeena Pharmaceuticals, iVeena Delivery 
      Systems and Inflammasome Therapeutics, and has received honoraria from Allergan 
      and research funding from Olix Pharmaceuticals unrelated to this work. JA and 
      SDeF are named as inventors on patent applications filed by the University of 
      Kentucky relating to the technology described in this work.
EDAT- 2016/03/01 06:00
MHDA- 2016/03/01 06:01
PMCR- 2016/01/28
CRDT- 2016/03/01 06:00
PHST- 2016/03/01 06:00 [entrez]
PHST- 2016/03/01 06:00 [pubmed]
PHST- 2016/03/01 06:01 [medline]
PHST- 2016/01/28 00:00 [pmc-release]
AID - 15002 [pii]
AID - 10.1038/sigtrans.2015.2 [doi]
PST - ppublish
SO  - Signal Transduct Target Ther. 2016;1:15002-. doi: 10.1038/sigtrans.2015.2. Epub 
      2016 Jan 28.