1. Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti‐HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients
- Author
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Lena Winstedt, Lars Björck, Britt Marie Eriksson, Christian Kjellman, Torsten Eich, Sofia Järnum, Tomas Lorant, Anna-Karin L. Robertson, Yvonne Stenberg, Lars Bäckman, Kathryn J. Wood, Mats Bengtsson, Gunnar Tufveson, Erik Larsson, and Kristina Mosén
- Subjects
0301 basic medicine ,Graft Rejection ,Male ,kidney transplantation/nephrology ,030230 surgery ,Pharmacology ,0302 clinical medicine ,HLA Antigens ,Isoantibodies ,Risk Factors ,Urologi och njurmedicin ,Immunology and Allergy ,Medicine ,Cytotoxic T cell ,Pharmacology (medical) ,living donor [kidney transplantation] ,histocompatibility ,Infusions, Intravenous ,Kidney ,biology ,Immunogenicity ,Graft Survival ,clinical trial ,Clinical Science ,Middle Aged ,Prognosis ,medicine.anatomical_structure ,Original Article ,Female ,pharmacokinetics/pharmacodynamics ,Antibody ,Adult ,Streptococcus pyogenes ,B-cell receptor ,desensitization ,clinical research/practice ,kidney transplantation: living donor ,03 medical and health sciences ,Pharmacokinetics ,Bacterial Proteins ,Urology and Nephrology ,Humans ,crossmatch ,Renal Insufficiency, Chronic ,Aged ,Transplantation ,business.industry ,Complement C1q ,medicine.disease ,Kidney Transplantation ,Histocompatibility ,030104 developmental biology ,Desensitization, Immunologic ,Immunoglobulin G ,biology.protein ,ORIGINAL ARTICLES ,business ,Kidney disease ,Follow-Up Studies - 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, In highly sensitized patients with chronic kidney disease, the immunoglobulin G–degrading enzyme of Streptococcus pyogenes (imlifidase) degrades plasma IgG efficiently, reduces HLA antibodies substantially, and abolishes C1q binding to anti‐HLA, thus enabling HLA‐incompatible kidney transplantation.
- Published
- 2018