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IgG Endopeptidase i...
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Jordan, Stanley CCedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
(författare)
IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation.
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
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Massachusetts Medical Society,2017
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-333282
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-333282URI
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https://doi.org/10.1056/NEJMoa1612567DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:136387872URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-346786URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Drs. Jordan and Lorant, and Drs. Vo and Tufveson, contributed equally to this article.
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BACKGROUND: Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.METHODS: We administered IdeS to 25 highly HLA-sensitized patients (11 patients in Uppsala or Stockholm, Sweden, and 14 in Los Angeles) before the transplantation of a kidney from an HLA-incompatible donor. Frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function was performed, as were renal biopsies. Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids. Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.RESULTS: Recipients in the U.S. study had a significantly longer cold ischemia time (the time elapsed between procurement of the organ and transplantation), a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study. A total of 38 serious adverse events occurred in 15 patients (5 events were adjudicated as being possibly related to IdeS). At transplantation, total IgG and HLA antibodies were eliminated. A total of 24 of 25 patients had perfusion of allografts after transplantation. Antibody-mediated rejection occurred in 10 patients (7 patients in the U.S. study and 3 in the Swedish study) at 2 weeks to 5 months after transplantation; all these patients had a response to treatment. One graft loss, mediated by non-HLA IgM and IgA antibodies, occurred.CONCLUSIONS: IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients. (Funded by Hansa Medical; ClinicalTrials.gov numbers, NCT02224820 , NCT02426684 , and NCT02475551 .).
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Lorant, Tomas,1975-Uppsala universitet,Transplantationskirurgi(Swepub:uu)tomalora
(författare)
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Choi, JuaCedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
(författare)
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Kjellman, Christian
(författare)
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Winstedt, Lena
(författare)
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Bengtsson, MatsUppsala universitet,Klinisk immunologi(Swepub:uu)matsbs
(författare)
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Zhang, Xiaohai
(författare)
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Eich, TorstenUppsala universitet,Klinisk immunologi(Swepub:uu)toeic517
(författare)
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Toyoda, Mieko
(författare)
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Eriksson, Britt-MarieUppsala universitet,Infektionssjukdomar,Institutionen för immunologi, genetik och patologi(Swepub:uu)breri424
(författare)
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Ge, Shili
(författare)
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Peng, Alice
(författare)
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Järnum, Sofia
(författare)
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Wood, Kathryn J
(författare)
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Lundgren, TorbjörnKarolinska Institutet
(författare)
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Wennberg, LarsKarolinska Institutet
(författare)
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Bäckman, LarsUppsala universitet,Transplantationskirurgi(Swepub:uu)larba545
(författare)
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Larsson, ErikUppsala universitet,Klinisk och experimentell patologi(Swepub:uu)eriklars
(författare)
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Villicana, Rafael
(författare)
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Kahwaji, Joe
(författare)
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Louie, Sabrina
(författare)
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Kang, Alexis
(författare)
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Haas, Mark
(författare)
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Nast, Cynthia
(författare)
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Vo, Ashley
(författare)
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Tufveson, GunnarUppsala universitet,Transplantationskirurgi(Swepub:uu)gutuf839
(författare)
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Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.Transplantationskirurgi
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:New England Journal of Medicine: Massachusetts Medical Society377:5, s. 442-4530028-47931533-4406
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- Av författaren/redakt...
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Jordan, Stanley ...
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Lorant, Tomas, 1 ...
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Choi, Jua
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Kjellman, Christ ...
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Winstedt, Lena
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Bengtsson, Mats
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visa fler...
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Zhang, Xiaohai
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Eich, Torsten
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Toyoda, Mieko
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Eriksson, Britt- ...
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Ge, Shili
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Peng, Alice
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Järnum, Sofia
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Wood, Kathryn J
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Lundgren, Torbjö ...
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Wennberg, Lars
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Bäckman, Lars
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Larsson, Erik
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Villicana, Rafae ...
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Kahwaji, Joe
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Louie, Sabrina
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Kang, Alexis
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Haas, Mark
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Nast, Cynthia
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Vo, Ashley
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Tufveson, Gunnar
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Uppsala universitet
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