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Safety, immunogenic...
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Lorant, Tomas,1975-Uppsala universitet,Uppsala University,Transplantationskirurgi
(author)
Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients
- Article/chapterEnglish2018
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LIBRIS-ID:oai:lup.lub.lu.se:2ae4db3b-b59d-4e03-becb-43214eb0229d
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https://lup.lub.lu.se/record/2ae4db3b-b59d-4e03-becb-43214eb0229dURI
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https://doi.org/10.1111/ajt.14733DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-366863URI
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
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Safety, immunogenicity, pharmacokinetics, and efficacy of the IgG-degrading enzyme of Streptococcus pyogenes (IdeS [imlifidase]) were assessed in a single-center, open-label ascending-dose study in highly sensitized patients with chronic kidney disease. Eight patients with cytotoxic PRAs (median cytotoxic PRAs of 64%) at enrollment received 1 or 2 intravenous infusions of IdeS on consecutive days (0.12 mg/kg body weight ×2 [n = 3]; 0.25 mg/kg ×1 [n = 3], or 0.25 mg/kg ×2 [n = 2]). IgG degradation was observed in all subjects after IdeS treatment, with <1% plasma IgG remaining within 48 hours and remaining low up to 7 days. Mean fluorescence intensity values of HLA class I and II reactivity were substantially reduced in all patients, and C1q binding to anti-HLA was abolished. IdeS also cleaved the IgG-type B cell receptor on CD19+ memory B cells. Anti-IdeS antibodies developed 1 week after treatment, peaking at 2 weeks. A few hours after the second IdeS infusion, 1 patient received a deceased donor kidney offer. At enrollment, the patient had a positive serum crossmatch (HLA-B7), detected by complement-dependent cytotoxicity, flow cytometry, and multiplex bead assays. After IdeS infusion (0.12 mg/kg ×2) and when the HLA-incompatible donor (HLA-B7+) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.
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Bengtsson, MatsUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)matsbs
(author)
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Eich, Torsten,1972-Uppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)toeic517
(author)
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Eriksson, Britt-Marie,Docent,1952-Uppsala universitet,Uppsala University,Infektionssjukdomar(Swepub:uu)breri424
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Winstedt, LenaHansa Medical AB, Lund, Sweden
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Järnum, SofiaHansa Medical AB, Lund, Sweden(Swepub:lu)nkir-sja
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Stenberg, YvonneHansa Medical AB, Lund, Sweden
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Robertson, Anna KarinHansa Medical AB, Lund, Sweden
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Mosén, KristinaHansa Medical AB, Lund, Sweden
(author)
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Björck, LarsLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden(Swepub:lu)medk-lbj
(author)
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Bäckman, LarsUppsala universitet,Uppsala University,Transplantationskirurgi(Swepub:uu)larba545
(author)
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Larsson, ErikUppsala universitet,Uppsala University,Klinisk och experimentell patologi(Swepub:uu)eriklars
(author)
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Wood, KathrynNuffield Department of Surgical Sciences, Oxford University, Oxford, UK
(author)
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Tufveson, GunnarUppsala universitet,Uppsala University,Transplantationskirurgi(Swepub:uu)gutuf839
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Kjellman, ChristianHansa Medical AB, Lund, Sweden(Swepub:lu)wbl-ckj
(author)
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Uppsala UniversityTransplantationskirurgi
(creator_code:org_t)
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In:American Journal of Transplantation: Elsevier BV18:11, s. 2752-27621600-61351600-6143
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Lorant, Tomas, 1 ...
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Bengtsson, Mats
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Eich, Torsten, 1 ...
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Eriksson, Britt- ...
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Winstedt, Lena
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Järnum, Sofia
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Stenberg, Yvonne
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Mosén, Kristina
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Björck, Lars
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