Donor specific antibodies (DSA) create an impenetrable immunologic barrier to transplantation. Current rx aimed at modification of DSAs are not effective in the most HS pts. The IgG degrading enzyme derived from S. pyogenes (IdeS) cleaves human IgG into F(ab')₂ & Fc fragments thus inhibiting complement dependent cytotoxicity (CDC) & antibody-dependent cellular cytotoxicity (ADCC). IdeS also cleaves the B-cell receptor off circulating B-cells, inhibiting IgG memory B-cell responses. This suggests that IdeS could be useful for desensitization (DES). Here, we report our experience using IdeS for DES & incompatible tx. Methods: 15 HS pts received IdeS immediately before kidney tx. Frequent monitoring for adverse events, alloantibodies, DSAs & renal function was performed. Post-transplant anti rejection included: tacrolimus, mycophenolate mofetil & steroids; & induction with Campath-1H. Pts also received IVIg + rituximab post-transplant to prevent antibody rebound. Results: All patients were HS (mean cPRA 95%). Pts received IdeS infusion 4-6 hrs prior to incompatible transplant. At transplant, total IgG & HLA antibodies were eliminated. Fourteen of 15 patients were successfully transplanted without discernable adverse events. ABMR occurred in 4 patients at mean 3.6M post-tx. All responded to treatment. One graft loss, mediated by non-HLA IgM & IgA antibodies, occurred. DSA level pre-DES & 1M post-Ides show a significant reduction p = 0.0047 (figure 1). Conclusions: 1) IdeS treatment completely eliminates DSAs & allows for successful transplantation of HLAi patients. 2) IdeS is generally well tolerated with acceptable adverse events. 3) IdeS may provide a more rapid and durable method to desensitize HLA sensitized patients, offering them the benefits of life-saving transplantation. Critical to the prevention of DSA rebound is the use of IVIg + rituximab ~ 1-2 weeks post-transplant.

CITATION INFORMATION: Jordan S, Choi J, Kjellman C, Winstedt L, Zhang X, Louie S, Kang A, Haas M, Vo A. Experience with the Bacterial Enzyme IdeS (IgG Endopeptidase) for Desensitization of Highly-HLA Sensitized (HS) Kidney Allograft Recipients. Am J Transplant. 2017;17 (suppl 3).

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