The complement receptor 2/factor H fusion protein TT30 protects paroxysmal nocturnal hemoglobinuria erythrocytes from complement-mediated hemolysis and C3 fragment.

Blood
Antonio M RisitanoV Michael Holers

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis because of the lack from erythrocyte surface of the complement regulators CD55 and CD59, with subsequent uncontrolled continuous spontaneous activation of the complement alternative pathway (CAP), and at times of the complement classic pathway. Here we investigate in an in vitro model the effect on PNH erythrocytes of a novel therapeutic strategy for membrane-targeted delivery of a CAP inhibitor. TT30 is a 65 kDa recombinant human fusion protein consisting of the iC3b/C3d-binding region of complement receptor 2 (CR2) and the inhibitory domain of the CAP regulator factor H (fH). TT30 completely inhibits in a dose-dependent manner hemolysis of PNH erythrocytes in a modified extended acidified serum assay, and also prevents C3 fragment deposition on surviving PNH erythrocytes. The efficacy of TT30 derives from its direct binding to PNH erythrocytes; if binding to the erythrocytes is disrupted, only partial inhibition of hemolysis is mediated by TT30 in solution, which is similar to that produced by the fH moiety of TT30 alone, or by intact human fH. TT30 is a membrane-targeted selective CAP inhibitor that may prevent both intr...Continue Reading

References

Nov 2, 1976·The Journal of Experimental Medicine·K Whaley, S Ruddy
Jan 1, 1988·Annual Review of Biochemistry·H J Müller-Eberhard
Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·M K PangburnH J Müller-Eberhard
Aug 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·A Nicholson-WellerK F Austen
Jan 1, 1983·Annals of the New York Academy of Sciences·M K Pangburn, H J Müller-Eberhard
Jan 1, 1993·International Reviews of Immunology·M Botto, M J Walport
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·A K Sharma, M K Pangburn
May 26, 1998·Scandinavian Journal of Immunology·M PeknaM Pekny
Nov 4, 1998·Seminars in Immunology·D T Fearon
Jul 25, 2000·Immunopharmacology·V M Holers
Nov 9, 2002·American Journal of Human Genetics·Pilar Sánchez-CorralSantiago Rodríguez de Córdoba
Jun 14, 2003·Clinical Immunology : the Official Journal of the Clinical Immunology Society·V Michael Holers
Feb 6, 2004·The New England Journal of Medicine·Peter HillmenRussell P Rother
May 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Gregory S HagemanRando Allikmets
Jul 30, 2005·Blood·Charles ParkerUNKNOWN International PNH Interest Group
Sep 23, 2006·The New England Journal of Medicine·Peter HillmenLucio Luzzatto
Apr 26, 2007·Blood·Sebastian KreilUNKNOWN German Chronic Myelogenous Leukemia (CML) Study Group
Nov 9, 2007·Nature Biotechnology·Daniel Ricklin, John D Lambris
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hongbin SongStephen Tomlinson
Dec 18, 2007·Clinical and Experimental Immunology·S Rodríguez de Córdoba, E Goicoechea de Jorge
Jul 11, 2008·Immunological Reviews·V Michael Holers
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuxiang HuangStephen Tomlinson
Mar 7, 2009·Investigative Ophthalmology & Visual Science·Bärbel RohrerStephen Tomlinson
Apr 10, 2010·Haematologica·Lucio LuzzattoRosario Notaro
Dec 3, 2010·The New England Journal of Medicine·Antonio M RisitanoPeter Hillmen

❮ Previous
Next ❯

Citations

Sep 8, 2015·Expert Review of Hematology·Wilma Barcellini
Jun 7, 2015·Journal of the American Society of Nephrology : JASN·Marieta M RusevaMatthew C Pickering
Oct 29, 2013·Seminars in Nephrology·Tomoko TakanoAndrey V Cybulsky
Sep 6, 2015·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Edimara S ReisJohn D Lambris
Feb 28, 2016·Experimental Hematology·Arthur J VaughtRobert A Brodsky
Oct 24, 2015·Nature Reviews. Drug Discovery·B Paul Morgan, Claire L Harris
Feb 8, 2016·American Journal of Hematology·Antonio M Risitano
Feb 14, 2015·European Journal of Clinical Investigation·Dimitrios C MastellosJohn D Lambris
Feb 24, 2015·European Journal of Haematology·Jörg Schubert, Alexander Röth
May 6, 2016·Frontiers in Cellular Neuroscience·M Akhtar AnwarAli H Eid
Jun 18, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
Jun 24, 2015·Immunobiology·Daniel Ricklin, John D Lambris
Jun 16, 2015·Frontiers in Immunology·Nicolas S MerleLubka T Roumenina
Jun 5, 2015·Hematology/oncology Clinics of North America·Antonio M Risitano
Jun 5, 2015·Hematology/oncology Clinics of North America·Amy E DeZern, Robert A Brodsky
May 20, 2015·Immunobiology·Yuzhou ZhangRichard J H Smith
Apr 1, 2015·Molecular Immunology·R B PouwD Wouters
Sep 23, 2014·Blood·Robert A Brodsky
Jan 31, 2015·Blood·Antonio M Risitano
Jun 28, 2016·Seminars in Immunology·Antonio M Risitano, Serena Marotta
Mar 24, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Z X YuY Wang
Oct 27, 2016·Immunological Reviews·Christoph Q SchmidtDaniel Ricklin
Oct 27, 2016·Immunological Reviews·Daniel RicklinJohn D Lambris
Mar 14, 2017·Bone Marrow Transplantation·E GavriilakiR A Brodsky
Jun 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Serena BettoniMarina Noris
Dec 5, 2017·Nature Reviews. Nephrology·Daniel RicklinJohn D Lambris
Oct 17, 2017·Journal of the American Society of Nephrology : JASN·Paraskevas IatropoulosUNKNOWN Nastasi
Oct 31, 2013·Expert Review of Clinical Immunology·Juan Carlos Varela, Robert A Brodsky
Jun 21, 2017·Journal of Hematology & Oncology·Michela SicaRosario Notaro
Feb 6, 2020·Expert Opinion on Biological Therapy·Jong Wook Lee, Austin G Kulasekararaj
Aug 13, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qian QiaoWeiguo Hu
Apr 26, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christoph Q SchmidtJohn D Lambris
Dec 9, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Markus J HarderChristoph Q Schmidt
Apr 9, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel Ricklin, John D Lambris
Apr 15, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Danielle Paixão-CavalcanteClaire L Harris
Jan 10, 2018·American Journal of Hematology·Antonio M Risitano, Serena Marotta
Mar 13, 2019·Der Internist·B HohensteinJ Menne

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.