Project description:Background: Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABO-incompatible (ABOi) kidney transplantation (KT). However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR. Methods: Eculizumab-based desensitization was used to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Results: The initial titers of anti-ABO IgG antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from the day of KT to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infectious complications, despite early episodes of suspicious AMR or borderline T cell-mediated rejection. Molecular phenotype analysis of allograft biopsies using the Banff Human Organ Transplant gene panel revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells at this time point. Conclusions: Short-term eculizumab-based desensitization therapy is promising for rescuing ABOi KT recipients with unacceptably high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.