IdeS: A Novel Agent that Cleaves Human IgG and Permits Successful Kidney Transplantation across High-Strength Donor-Specific Antibody
Bonnie E. Lonze*, Vasishta S. Tatapudi*, Elaina P. Weldon*, Elijah S. Min*, Nicole M. Ali*, Cecilia L. Deterville*, Bruce E. Gelb*, Judith A. Benstein*, Nabil N. Dagher*, Ming Wu*, Robert A. Montgomery
NYU Langone Transplant Institute, New York, NY
OBJECTIVE(S): To prevent hyperacute rejection, transplant recipients who have pre-formed donor-specific antibody (DSA) must undergo desensitization prior to transplantation. Traditionally, this involves plasmpheresis treatments that occur over days to weeks. Desensitization has only been feasible when there is a living donor and the date of the transplant is known, allowing time for plasmapheresis. For sensitized patients without a living donor, transplantation has been historically difficult. IdeS is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and, when infused intravenously can result in rapid cleavage of all IgG.
METHODS: Here we present the results of a single-center IRB approved study involving 7 highly-sensitized (PRA99-100%) kidney transplant candidates with DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant.
RESULTS: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. 3 patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. 3 patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 171 days.
CONCLUSIONS: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.
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