The Korean journal of internal medicine

  • 제33권1호
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  • Pages.157-167
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  • 2018
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  • 1226-3303(pISSN)
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  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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Clinical significance of the presence of anti-human leukocyte antigen-donor specific antibody in kidney transplant recipients with allograft dysfunction

  • Chung, Byung Ha (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Kim, Jeong Ho (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Choi, Bum Soon (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Park, Cheol Whee (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Kim, Ji-Il (Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Moon, In Sung (Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Kim, Yong-Soo (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Choi, Yeong Jin (Department of Hospital Pathology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Oh, Eun-Jee (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Yang, Chul Woo (Transplant Research Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 투고 : 2016.03.30
  • 심사 : 2016.05.28
  • 발행 : 2018.01.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background/Aims: This study investigated the clinical significance of detecting anti-human leukocyte antigen-donor specific antibody (HLA-DSA) in kidney transplant recipients (KTRs) requiring indication biopsy owing to allograft dysfunction. Methods: We analyzed the presence of HLA-DSA in 210 KTRs who took indication biopsy. We divided these cases into two groups, HLA-DSA (+) (n = 52) and HLA-DSA (-) (n = 158) group, and compared the clinical characteristics, pathological findings, and clinical outcomes of the two groups. Results: The rates of retransplant, pretransplant sensitization, and HLA-mismatch were significantly higher in HLA-DSA (+) group than in HLA-DSA (-) group (p < 0.05 for each comparison). In histologic finding, all types of rejections were more frequent in the former group. Besides, scores of both the T-cell injury markers such as tubulitis, interstitial inf lammation, and vasculitis and antibody-mediated injury markers such as peritubular C4d deposition and microvascular inflammation (glomerulitis plus peritubular capillaritis) were higher in HLA-DSA (+) group (p < 0.05 for each). Notably, allograft outcomes were worse in HLA-DSA (+) group. Further, multivariate analysis showed that presence of HLA-DSA, advanced interstitial fibrosis/tubular atrophy (interstitial fibrosis plus tubular atrophy ${\geq}2$), and allograft rejection in biopsy were independent risk factors for allograft failure. Conclusions: The results of this study showed that presence of HLA-DSA in a case of allograft dysfunction adversely influences allograft outcome, and its detection, irrespective of the result of the allograft biopsy, necessitates intensive monitoring and treatment.

키워드

과제정보

연구 과제 주관 기관 : Ministry of Health and Welfare

참고문헌

  1. Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012;12:1157-1167. https://doi.org/10.1111/j.1600-6143.2012.04013.x
  2. 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
  3. Sellares J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012;12:388-399. https://doi.org/10.1111/j.1600-6143.2011.03840.x
  4. Cosio FG, Gloor JM, Sethi S, Stegall MD. Transplant glomerulopathy. Am J Transplant 2008;8:492-496. https://doi.org/10.1111/j.1600-6143.2007.02104.x
  5. Everly MJ, Rebellato LM, Haisch CE, et al. Incidence and impact of de novo donor-specific alloantibody in primary renal allografts. Transplantation 2013;95:410-417. https://doi.org/10.1097/TP.0b013e31827d62e3
  6. Dieplinger G, Ditt V, Arns W, et al. Impact of de novo donor-specific HLA antibodies detected by Luminex solid-phase assay after transplantation in a group of 88 consecutive living-donor renal transplantations. Transpl Int 2014;27:60-68. https://doi.org/10.1111/tri.12207
  7. Dieplinger G, Everly MJ, Rebellato LM, et al. Changes in successive measures of de novo donor-specific anti-human leukocyte antigen antibodies intensity and the development of allograft dysfunction. Transplantation 2014;98:1097-1104. https://doi.org/10.1097/TP.0000000000000190
  8. Chung BH, Lee JY, Kang SH, et al. Comparison of clinical outcome between high and low baseline anti-ABO antibody titers in ABO-incompatible kidney transplantation. Ren Fail 2011;33:150-158. https://doi.org/10.3109/0886022X.2011.552149
  9. Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 2008;8:753-760. https://doi.org/10.1111/j.1600-6143.2008.02159.x
  10. Haas M, Sis B, Racusen LC, et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014;14:272-283. https://doi.org/10.1111/ajt.12590
  11. Cooper JE, Gralla J, Chan L, Wiseman AC. Clinical significance of post kidney transplant de novo DSA in otherwise stable grafts. Clin Transpl 2011:359-364.
  12. Chung BH, Choi BS, Oh EJ, et al. Clinical impact of the baseline donor-specific anti-human leukocyte antigen antibody measured by Luminex single antigen assay in living donor kidney transplant recipients after desensitization therapy. Transpl Int 2014;27:49-59. https://doi.org/10.1111/tri.12199
  13. Chung BH, Joo YY, Lee J, et al. Impact of ABO incompatibility on the development of acute antibody-mediated rejection in kidney transplant recipients presensitized to HLA. PLoS One 2015;10:e0123638. https://doi.org/10.1371/journal.pone.0123638
  14. Armstrong KA, Campbell SB, Hawley CM, Nicol DL, Johnson DW, Isbel NM. Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients. Am J Transplant 2005;5:2710-2718. https://doi.org/10.1111/j.1600-6143.2005.01073.x
  15. Vlad G, Ho EK, Vasilescu ER, et al. Relevance of different antibody detection methods for the prediction of antibody- mediated rejection and deceased-donor kidney allograft survival. Hum Immunol 2009;70:589-594. https://doi.org/10.1016/j.humimm.2009.04.018
  16. Caro-Oleas JL, Gonzalez-Escribano MF, Gonzalez-Roncero FM, et al. Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation. Nephrol Dial Transplant 2012;27:1231-1238. https://doi.org/10.1093/ndt/gfr429
  17. Hwang HS, Sun IO, Yoon HE, et al. Antibody monitoring system to support the single-antigen Luminex assay in donor-specific antibody detection. Hum Immunol 2012;73:370-375. https://doi.org/10.1016/j.humimm.2012.01.017
  18. Ntokou IS, Iniotaki AG, Kontou EN, et al. Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules. Transpl Int 2011;24:1084-1093. https://doi.org/10.1111/j.1432-2277.2011.01312.x
  19. Gloor JM, Cosio FG, Rea DJ, et al. Histologic findings one year after positive crossmatch or ABO blood group incompatible living donor kidney transplantation. Am J Transplant 2006;6:1841-1847. https://doi.org/10.1111/j.1600-6143.2006.01416.x
  20. Ishida H, Furusawa M, Shimizu T, Nozaki T, Tanabe K. Influence of preoperative anti-HLA antibodies on shortand long-term graft survival in recipients with or without rituximab treatment. Transpl Int 2014;27:371-382. https://doi.org/10.1111/tri.12267
  21. Lachmann N, Terasaki PI, Budde K, et al. Anti-human leukocyte antigen and donor-specific antibodies detected by luminex posttransplant serve as biomarkers for chronic rejection of renal allografts. Transplantation 2009;87:1505-1513. https://doi.org/10.1097/TP.0b013e3181a44206
  22. Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med 2003;349:2326-2333. https://doi.org/10.1056/NEJMoa020009
  23. Thomas WR, Hales BJ. T and B cell responses to HDM allergens and antigens. Immunol Res 2007;37:187-199. https://doi.org/10.1007/BF02697369
  24. Ramiscal RR, Vinuesa CG. T-cell subsets in the germinal center. Immunol Rev 2013;252:146-155. https://doi.org/10.1111/imr.12031
  25. Qi H. From SAP-less T cells to helpless B cells and back: dynamic T-B cell interactions underlie germinal center development and function. Immunol Rev 2012;247:24-35. https://doi.org/10.1111/j.1600-065X.2012.01119.x
  26. Naemi FM, Carter V, Kirby JA, Ali S. Anti-donor HLA class I antibodies: pathways to endothelial cell activation and cell-mediated allograft rejection. Transplantation 2013;96:258-266. https://doi.org/10.1097/TP.0b013e3182985504
  27. Lobo LJ, Aris RM, Schmitz J, Neuringer IP. Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation. J Heart Lung Transplant 2013;32:70-27. https://doi.org/10.1016/j.healun.2012.10.007
  28. Sis B, Jhangri GS, Riopel J, et al. A new diagnostic algorithm for antibody-mediated microcirculation inflammation in kidney transplants. Am J Transplant 2012;12:1168-1179. https://doi.org/10.1111/j.1600-6143.2011.03931.x
  29. de Kort H, Willicombe M, Brookes P, et al. Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies. Am J Transplant 2013;13:485-492. https://doi.org/10.1111/j.1600-6143.2012.04325.x
  30. Loupy A, Hill GS, Jordan SC. The impact of donor-specific anti-HLA antibodies on late kidney allograft failure. Nat Rev Nephrol 2012;8:348-357.
  31. Aubert V, Venetz JP, Pantaleo G, Pascual M. Low levels of human leukocyte antigen donor-specific antibodies detected by solid phase assay before transplantation are frequently clinically irrelevant. Hum Immunol 2009;70:580-583. https://doi.org/10.1016/j.humimm.2009.04.011