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Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients

Lorant, Tomas; Bengtsson, Mats LU ; Eich, Torsten; Eriksson, Britt Marie; Winstedt, Lena; Järnum, Sofia LU ; Stenberg, Yvonne; Robertson, Anna Karin; Mosén, Kristina and Björck, Lars LU , et al. (2018) In American Journal of Transplantation 18(11). p.2752-2762
Abstract

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,... (More)

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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published
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keywords
Clinical research/practice, Clinical trial, Crossmatch, Desensitization, Histocompatibility, Kidney transplantation/nephrology, Kidney transplantation: living donor, Pharmacokinetics/pharmacodynamics
in
American Journal of Transplantation
volume
18
issue
11
pages
2752 - 2762
publisher
Wiley-Blackwell
external identifiers
  • scopus:85045747909
ISSN
1600-6135
DOI
10.1111/ajt.14733
language
English
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yes
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2ae4db3b-b59d-4e03-becb-43214eb0229d
date added to LUP
2018-05-04 13:57:58
date last changed
2019-09-17 04:31:40
@article{2ae4db3b-b59d-4e03-becb-43214eb0229d,
  abstract     = {<p>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 &lt;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<sup>+</sup> 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<sup>+</sup>) kidney was offered, the HLA antibody profile was negative. The kidney was transplanted successfully.</p>},
  author       = {Lorant, Tomas and Bengtsson, Mats and Eich, Torsten and Eriksson, Britt Marie and Winstedt, Lena and Järnum, Sofia and Stenberg, Yvonne and Robertson, Anna Karin and Mosén, Kristina and Björck, Lars and Bäckman, Lars and Larsson, Erik and Wood, Kathryn and Tufveson, Gunnar and Kjellman, Christian},
  issn         = {1600-6135},
  keyword      = {Clinical research/practice,Clinical trial,Crossmatch,Desensitization,Histocompatibility,Kidney transplantation/nephrology,Kidney transplantation: living donor,Pharmacokinetics/pharmacodynamics},
  language     = {eng},
  number       = {11},
  pages        = {2752--2762},
  publisher    = {Wiley-Blackwell},
  series       = {American Journal of Transplantation},
  title        = {Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients},
  url          = {http://dx.doi.org/10.1111/ajt.14733},
  volume       = {18},
  year         = {2018},
}