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Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti‐ HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients
Author(s) -
Lorant Tomas,
Bengtsson Mats,
Eich Torsten,
Eriksson BrittMarie,
Winstedt Lena,
Järnum Sofia,
Stenberg Yvonne,
Robertson AnnaKarin,
Mosén Kristina,
Björck Lars,
Bäckman Lars,
Larsson Erik,
Wood Kathryn,
Tufveson Gunnar,
Kjellman Christian
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14733
Subject(s) - immunogenicity , medicine , pharmacokinetics , antibody , kidney , immunology , cytotoxic t cell , kidney disease , pharmacology , chemistry , in vitro , biochemistry
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 CD 19 + 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.