The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Proteasome-Inhibitor-Based Primary Therapy for Antibody-Mediated Rejection in a Renal Transplant Recipient

신이식 환자의 항체매개성 거부반응에서 Bortezomib으로 치료한 1예

  • Park, Se-Jeong (Department of Internal Meidicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Yu, Hoon (Department of Internal Meidicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kang, Sung-Hee (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Baek, Seung-Don (Department of Internal Meidicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Baek, Chung-Hee (Department of Internal Meidicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Jeong, Jae-Ho (Department of Internal Meidicine, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Park, Su-Kil (Department of Division of Nephrology, University of Ulsan College of Medicine, Asan Medical Center)
  • 박세정 (울산대학교 의과대학 서울아산병원 내과) ;
  • 유훈 (울산대학교 의과대학 서울아산병원 내과) ;
  • 강성희 (울산대학교 의과대학 서울아산병원 병리과) ;
  • 백승돈 (울산대학교 의과대학 서울아산병원 내과) ;
  • 백충희 (울산대학교 의과대학 서울아산병원 내과) ;
  • 정재호 (울산대학교 의과대학 서울아산병원 내과) ;
  • 박수길 (울산대학교 의과대학 서울아산병원 신장내과)
  • Published : 2011.12.01
⟨ Previous Next ⟩

Abstract

Donor-specific anti-human leukocyte antigen antibodies (DSA) following kidney transplantation predict the evolution of humoral rejection and reduced graft survival. Rapid, complete elimination of DSA during antibody-mediated rejection (AMR) is rarely achieved with traditional antihumoral therapies. We report the case of a 39-year-old female who was admitted for increasing azotemia and diagnosed with AMR based on diffusely positive histological changes on C4d immunostaining. In this case, bortezomib reversed the histological changes and induced a reduction in DSA. Proteasome-inhibitor-based combination therapy is a potential means for rapid DSA elimination in antibody-mediated rejection in renal transplant recipients.

공여자 특이 항체는 이식신 부전의 주요 원인이 되며 이를 효과적으로 제거하는 것은 이전의 치료 방법을 통해서는 충분히 달성되지 못했다. 저자들은 39세 여자 환자로 신기능 저하로 입원하여 신조직 검사에서 C4d 미만성 양성 소견 및 혈중 공여자 특이 항체의 존재로 항체 매개 거부 반응을 진단받았고, 프로테아좀 억제제인 bortezomib을 통해 조직학적 소견의 호전 및 혈중 공여자 특이 항체의 감소와 이식신 기능회복을 가져온 증례를 경험하였기에 이를 보고한다.

Keywords

References

  1. Everly MJ, Everly JJ, Arend LJ, et al. Reducing de novo donor-specific antibody levels during acute rejection diminishes renal allograft loss. Am J Transplant 2009;9:1063-1071. https://doi.org/10.1111/j.1600-6143.2009.02577.x
  2. Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003;3:665-673. https://doi.org/10.1034/j.1600-6143.2003.00135.x
  3. Everly MJ, Everly JJ, Susskind B, et al. Bortezomib provides effective therapy for antibody- and cell-mediated acute rejection. Transplantation 2008;86:1754-1761. https://doi.org/10.1097/TP.0b013e318190af83
  4. Ramos EJ, Pollinger HS, Stegall MD, Gloor JM, Dogan A, Grande JP. The effect of desensitization protocols on human splenic B-cell populations in vivo. Am J Transplant 2007;7:402-407. https://doi.org/10.1111/j.1600-6143.2006.01632.x
  5. Walsh RC, Everly JJ, Brailey P, et al. Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection. Transplantation 2010;89:277-284. https://doi.org/10.1097/TP.0b013e3181c6ff8d
  6. Idica A, Kaneku H, Everly MJ, et al. Elimination of posttransplant donor-specific HLA antibodies with bortezomib. Clin Transpl 2008:229-239.
  7. Scornik JC, Salomon DR, Lim PB, Howard RJ, Pfaff WW. Posttransplant antidonor antibodies and graft rejection: evaluation by two-color flow cytometry. Transplantation 1989;47:287-290. https://doi.org/10.1097/00007890-198902000-00018
  8. Sis B, Mengel M, Haas M, et al. Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 2010;10:464-471. https://doi.org/10.1111/j.1600-6143.2009.02987.x
  9. Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation 2008;86:377-383.
  10. Worthington JE, Martin S, Al-Husseini DM, Dyer PA, Johnson RW. Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome. Transplantation 2003;75:1034-1040.
  11. Lee PC, Terasaki PI, Takemoto SK, et al. All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies. Transplantation 2002;74:1192-1194. https://doi.org/10.1097/00007890-200210270-00025
  12. Kraus ES, Parekh RS, Oberai P, et al. Subclinical rejection in stable positive crossmatch kidney transplant patients: incidence and correlations. Am J Transplant 2009;9:1826-1834. https://doi.org/10.1111/j.1600-6143.2009.02701.x
  13. Shah A, Nadasdy T, Arend L, et al. Treatment of C4d-positive acute humoral rejection with plasmapheresis and rabbit polyclonal antithymocyte globulin. Transplantation 2004;77:1399-1405. https://doi.org/10.1097/01.TP.0000122187.76518.BC
  14. Kaposztas Z, Podder H, Mauiyyedi S, et al. Impact of rituximab therapy for treatment of acute humoral rejection. Clin Transplant 2009;23:63-73. https://doi.org/10.1111/j.1399-0012.2008.00902.x