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 15 December 2017

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News

Novel therapy for highly sensitized patients undergoing transplant

This week's issue of the New England Journal of Medicine examines IgG endopeptidase in highly sensitized patients undergoing transplantation.

News image

Donor-specific antibodies create an immunologic barrier to transplantation.

Current therapies to modify donor-specific antibodies are limited, and ineffective in the most highly HLA-sensitized patients.

The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab′)2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization.

Dr Stanley Jordan and colleagues reported on the combined experience of 2 independently performed open-label, phase 1–2 trials that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.

The research team administered IdeS to 25 highly HLA-sensitized patients before the transplantation of a kidney from an HLA-incompatible donor.

Patients received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound
New England Journal of Medicine

The team performed frequent monitoring for adverse events, outcomes, donor-specific antibodies, and renal function, as were renal biopsies.

Immunosuppression after transplantation consisted of tacrolimus, mycophenolate mofetil, and glucocorticoids.

Patients in the U.S. study also received intravenous immune globulin and rituximab after transplantation to prevent antibody rebound.

The researchers found that recipients in the U.S. study had a significantly longer cold ischemia time, a significantly higher rate of delayed graft function, and significantly higher levels of class I donor-specific antibodies than those in the Swedish study.

A total of 38 serious adverse events occurred in 15 patients.

At transplantation, the team observed that total IgG and HLA antibodies were eliminated.

A total of 24 of 25 patients had perfusion of allografts after transplantation.

The researchers found that antibody-mediated rejection occurred in 10 patients at 2 weeks to 5 months after transplantation, and all these patients had a response to treatment.

The team reported 1 graft loss, mediated by non-HLA IgM and IgA antibodies.

Dr Jordan's team comments, "IdeS reduced or eliminated donor-specific antibodies, and permitted HLA-incompatible transplantation in 24 of 25 patients."

NEJM 2017; 377:442-453
03 August 2017

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