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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

Publisher, publication year, extent ...

  • Elsevier BV,2018

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:2ae4db3b-b59d-4e03-becb-43214eb0229d
  • https://lup.lub.lu.se/record/2ae4db3b-b59d-4e03-becb-43214eb0229dURI
  • https://doi.org/10.1111/ajt.14733DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-366863URI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Bengtsson, MatsUppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)matsbs (author)
  • Eich, Torsten,1972-Uppsala universitet,Uppsala University,Klinisk immunologi(Swepub:uu)toeic517 (author)
  • Eriksson, Britt-Marie,Docent,1952-Uppsala universitet,Uppsala University,Infektionssjukdomar(Swepub:uu)breri424 (author)
  • Winstedt, LenaHansa Medical AB, Lund, Sweden (author)
  • Järnum, SofiaHansa Medical AB, Lund, Sweden(Swepub:lu)nkir-sja (author)
  • Stenberg, YvonneHansa Medical AB, Lund, Sweden (author)
  • Robertson, Anna KarinHansa Medical AB, Lund, Sweden (author)
  • Mosén, KristinaHansa Medical AB, Lund, Sweden (author)
  • 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)
  • Bäckman, LarsUppsala universitet,Uppsala University,Transplantationskirurgi(Swepub:uu)larba545 (author)
  • Larsson, ErikUppsala universitet,Uppsala University,Klinisk och experimentell patologi(Swepub:uu)eriklars (author)
  • Wood, KathrynNuffield Department of Surgical Sciences, Oxford University, Oxford, UK (author)
  • Tufveson, GunnarUppsala universitet,Uppsala University,Transplantationskirurgi(Swepub:uu)gutuf839 (author)
  • Kjellman, ChristianHansa Medical AB, Lund, Sweden(Swepub:lu)wbl-ckj (author)
  • Uppsala UniversityTransplantationskirurgi (creator_code:org_t)

Related titles

  • In:American Journal of Transplantation: Elsevier BV18:11, s. 2752-27621600-61351600-6143

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