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Safety profile afte...
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Reis, Edimara S.Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
Safety profile after prolonged C3 inhibition
- Article/chapterEnglish2018
Publisher, publication year, extent ...
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Elsevier BV,2018
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printrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-373239
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-373239URI
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https://doi.org/10.1016/j.clim.2018.09.004DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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The central component of the complement cascade, C3, is involved in various biological functions, including opsonization of foreign bodies, clearance of waste material, activation of immune cells, and triggering of pathways controlling development. Given its broad role in immune responses, particularly in phagocytosis and the clearance of microbes, a deficiency in complement C3 in humans is often associated with multiple bacterial infections. Interestingly, an increased susceptibility to infections appears to occur mainly in the first two years of life and then wanes throughout adulthood. In view of the well-established connection between C3 deficiency and infections, therapeutic inhibition of complement at the level of C3 is often considered with caution or disregarded. We therefore set out to investigate the immune and biochemical profile of non-human primates under prolonged treatment with the C3 inhibitor compstatin (Cp40 analog). Cynomolgus monkeys were dosed subcutaneously with Cp40, resulting in systemic inhibition of C3, for 1 week, 2 weeks, or 3 months. Plasma concentrations of both C3 and Cp40 were measured periodically and complete saturation of plasma C3 was confirmed. No differences in hematological, biochemical, or immunological parameters were identified in the blood or tissues of animals treated with Cp40 when compared to those injected with vehicle alone. Further, skin wounds showed no signs of infection in those treated with Cp40. In fact, Cp40 treatment was associated with a trend toward accelerated wound healing when compared with the control group. In addition, a biodistribution study in a rhesus monkey indicated that the distribution of Cp40 in the body is associated with the presence of C3, concentrating in organs that accumulate blood and produce C3. Overall, our data suggest that systemic C3 inhibition in healthy adult non-human primates is not associated with a weakened immune system or susceptibility to infections.
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Added entries (persons, corporate bodies, meetings, titles ...)
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Berger, NadjaUniv Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
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Wang, XinUniv Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
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Koutsogiannaki, SophiaUniv Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
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Doot, Robert K.Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA
(author)
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Gumas, Justin T.Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
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Foukas, Periklis G.Univ Athens, Attikon Univ Hosp, Dept Pathol 2, Athens, Greece
(author)
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Resuello, Ranillo R. G.Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines
(author)
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Tuplano, Joel V.Simian Conservat Breeding & Res Ctr SICONBREC, Makati, Philippines
(author)
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Kukis, DavidUniv Calif Davis, Ctr Mol & Genom Imaging, Davis, CA 95616 USA
(author)
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Tarantal, Alice F.Univ Calif Davis, Sch Med, Dept Pediat, Davis, CA 95616 USA;Univ Calif Davis, Sch Med, Dept Cell Biol & Human Anat, Davis, CA 95616 USA;Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA
(author)
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Young, Anthony J.Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA
(author)
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Kajikawa, TetsuhiroUniv Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA
(author)
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Soulika, Athena M.Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA
(author)
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Mastellos, Dimitrios C.Natl Ctr Sci Res Demokritos, Athens, Greece
(author)
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Yancopoulou, DespinaAmyndas Pharmaceut, Glifadha, Greece
(author)
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Biglarnia, Ali-RezaLund Univ, Skane Univ Hosp, Dept Transplantat, Lund, Sweden
(author)
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Huber-Lang, MarkusUniv Hosp Ulm, Inst Clin & Expt Trauma Immunol, Ulm, Germany
(author)
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Hajishengallis, GeorgeUniv Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA
(author)
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Nilsson, BoUppsala universitet,Klinisk immunologi(Swepub:uu)bonils
(author)
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Lambris, John D.Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
(author)
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Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USAUniv Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA
(creator_code:org_t)
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In:Clinical Immunology: Elsevier BV197, s. 96-1061521-66161521-7035
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Reis, Edimara S.
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Doot, Robert K.
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Gumas, Justin T.
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