IgG-Degrading Enzyme Desensitizes, Permits HLA-Incompatible Transplant
IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation.
(HealthDay News) — The immunoglobulin G (IgG)-degrading enzyme derived from Streptococcus pyogenes (IdeS) reduces or eliminates donor-specific antibodies, allowing human leukocyte antigen (HLA)-incompatible kidney transplantation, according to the combined results of two phase 1-2 studies published in the New England Journal of Medicine.
Stanley C. Jordan, MD, from Cedars-Sinai Medical Center in Los Angeles, and colleagues administered IdeS to 25 highly HLA-sensitized patients (11 from Sweden and 14 from the United States) before kidney transplantation from an HLA-incompatible donor. The authors performed frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function, as well as renal biopsies.
The researchers found that the cold ischemia time (time between procurement of organ and transplantation) was significantly longer for the recipients in the US study, and they also had a significantly higher rate of delayed graft function and significantly higher levels of class I donor-specific antibodies compared to the recipients in the Swedish study. There were 38 serious adverse events in 15 patients. Total IgG and HLA antibodies were eliminated at transplantation; 24 patients had allograft perfusion after transplantation. At 2 weeks to 5 months after treatment, 10 patients had antibody-mediated rejection (7 in the US study and 3 in the Swedish study); all had a response to treatment.
"IdeS reduced or eliminated donor-specific antibodies and permitted HLA-incompatible transplantation in 24 of 25 patients," the authors write.
The study was funded by a research grant from Hansa Medical.
- Jordan SC, Lorant T, Choi J, et al. IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation. N Engl J Med. 3 August 2017. doi: 10.1056/NEJMoa1612567