Skip to main content

BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1465851
This article is part of the Research Topic Novel Therapeutic Targets for Alloimmune Injury in Solid Organ Transplantation View all 5 articles

Successful eculizumab treatment as an adjunctive therapy to desensitization in ABO-incompatible living donor kidney transplantation and its molecular phenotypes

Provisionally accepted
Ga Y. Heo Ga Y. Heo 1Minsun Jung Minsun Jung 1Honglin Piao Honglin Piao 1Hyun J. Kim Hyun J. Kim 1Hyung Woo Kim Hyung Woo Kim 1Juhan Lee Juhan Lee 1Kyu Ha Huh Kyu Ha Huh 1Beom Seok Kim Beom Seok Kim 1JAESEOK YANG JAESEOK YANG 1,2*
  • 1 Yonsei University, Seoul, Republic of Korea
  • 2 Yonsei University Health System, Seoul, Seoul, Republic of Korea

The final, formatted version of the article will be published soon.

    Introduction: ABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi 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 treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively.The initial titers of anti-ABO 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 KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis 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.Conclusions: Short-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.

    Keywords: ABO-incompatible kidney transplantation, Antibody-mediated Rejection, complement, Desensitization, Eculizumab

    Received: 17 Jul 2024; Accepted: 09 Oct 2024.

    Copyright: © 2024 Heo, Jung, Piao, Kim, Kim, Lee, Huh, Kim and YANG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: JAESEOK YANG, Yonsei University, Seoul, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.