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Single fixed low-dose rituximab as induction therapy suppresses de novo donor-specific anti-HLA antibody production in ABO compatible living kidney transplant recipients


Autoři: Yusuke Tomita aff001;  Kazuhiro Iwadoh aff001;  Yuichi Ogawa aff001;  Katsuyuki Miki aff001;  Yojiro Kato aff001;  Kotaro Kai aff001;  Akihito Sannomiya aff001;  Ichiro Koyama aff001;  Kumiko Kitajima aff001;  Ichiro Nakajima aff001;  Shohei Fuchinoue aff001
Působiště autorů: Department of Surgery, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224203

Souhrn

This study was conducted to evaluate de novo donor-specific anti-human leukocyte antigen (HLA) antibody (dnDSA) production leading to antibody-mediated rejection (ABMR) after rituximab induction in non-sensitized ABO-compatible living kidney transplantation (ABO-CLKTx). During 2008–2015, 318 ABO-CLKTx were performed at the Department of Surgery III at Tokyo Women’s Medical University Hospital. To reduce confounding factors, we adopted a propensity score analysis, which was applied with adjustment for age, gender, duration of pretransplant dialysis, HLA mismatch count, preformed DSA, non-insulin-dependent diabetes mellitus, immunosuppressive treatment, and estimated glomerular filtration rate (eGFR) on postoperative day 7. Using a propensity score matching model (1:1, 115 pairs), we analyzed the long-term outcomes of 230 ABO-CLKTx recipients retrospectively. Recipients were classified into a rituximab-treated (RTX-KTx, N = 115) group and a control group not treated with rituximab (C-KTx, N = 115). During five years, adverse events, survival rates for grafts and patients, and incidence of biopsy-proven acute rejection (BPAR) and dnDSA production for the two groups were monitored and compared. All recipients in the RTX-KTx group received rituximab induction on preoperative day 4 at a single fixed low dose of 100 mg; the CD19+ B cells were eliminated completely before surgery. Of those recipients, 13 (11.3%) developed BPAR; 1 (0.8%) experienced graft loss. By contrast, of C-KTx group recipients, 25 (21.7%) developed BPAR; 3 (2.6%) experienced graft loss. The RTX-KTx group exhibited a significantly lower incidence of BPAR (P = .041) and dnDSA production (13.9% in the RTX-KTx group vs. 26.9% in the C-RTx group, P = .005). Furthermore, lower incidence of CMV infection was detected in the RTX-KTx group than in the C-KTx group (13.9% in the RTX-KTx group vs. 27.0% in the C-KTx group, P = .014). No significant difference was found between groups for several other factors: renal function (P = .384), graft and patient survival (P = .458 and P = .119, respectively), and the respective incidences of BK virus infection (P = .722) and leukopenia (P = .207). During five-year follow-up, single fixed low-dose rituximab therapy is sufficient for ensuring safety, reducing rejection, and suppressing dnDSA production for immunological low-risk non-sensitized ABO-CLKTx.

Klíčová slova:

B cells – Flow cytometry – Graft survival – Immune suppression – Inflammation – Kidneys – Renal transplantation – T cells


Zdroje

1. Sawada T, Fuchinoue S, Teraoka S. Successful A1-to-O ABO-incompatible kidney transplantation after a preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy, and double-filtration plasmapheresis. Transplantation. 2002;74(9):1207–10. doi: 10.1097/00007890-200211150-00001 12451255.

2. Sawada T, Fuchinoue S, Kawase T, Kubota K, Teraoka S. Preconditioning regimen consisting of anti-CD20 monoclonal antibody infusions, splenectomy and DFPP-enabled non-responders to undergo ABO-incompatible kidney transplantation. Clin Transplant. 2004;18(3):254–60. doi: 10.1111/j.1399-0012.2004.00151.x 15142045.

3. Tydén G, Kumlien G, Genberg H, Sandberg J, Lundgren T, Fehrman I. ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab. Am J Transplant. 2005;5(1):145–8. doi: 10.1111/j.1600-6143.2004.00653.x 15636623.

4. Tanabe K, Ishida H, Shimizu T, Omoto K, Shirakawa H, Tokumoto T. Evaluation of two different preconditioning regimens for ABO-incompatible living kidney donor transplantation. A comparison of splenectomy vs. rituximab-treated non-splenectomy preconditioning regimens. Contrib Nephrol. 2009;162:61–74. Epub 2008/10/31. doi: 10.1159/000170813 19001814.

5. Fuchinoue S, Ishii Y, Sawada T, Murakami T, Iwadoh K, Sannomiya A et al. The 5-year outcome of ABO-incompatible kidney transplantation with rituximab induction. Transplantation. 2011;91(8):853–7. doi: 10.1097/TP.0b013e31820f08e8 21297552.

6. Mao Q, Terasaki PI, Cai J, Briley K, Catrou P, Haisch C et al. Extremely high association between appearance of HLA antibodies and failure of kidney grafts in a five-year longitudinal study. Am J Transplant. 2007;7(4):864–71. doi: 10.1111/j.1600-6143.2006.01711.x 17391129.

7. Gloor JM, Sethi S, Stegall MD, Park WD, Moore SB, DeGoey S et al. Transplant glomerulopathy: subclinical incidence and association with alloantibody. Am J Transplant. 2007;7(9):2124–32. Epub 2007/07/03. doi: 10.1111/j.1600-6143.2007.01895.x 17608832.

8. Loupy A, Lefaucheur C. Antibody-Mediated Rejection of Solid-Organ Allografts. N Engl J Med. 2018;379(12):1150–60. doi: 10.1056/NEJMra1802677 30231232.

9. Maloney DG, Grillo-López AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood. 1997;90(6):2188–95. 9310469.

10. Genberg H, Hansson A, Wernerson A, Wennberg L, Tydén G. Pharmacodynamics of rituximab in kidney allotransplantation. Am J Transplant. 2006;6(10):2418–28. Epub 2006/08/21. doi: 10.1111/j.1600-6143.2006.01497.x 16925569.

11. Stroopinsky D, Katz T, Rowe JM, Melamed D, Avivi I. Rituximab-induced direct inhibition of T-cell activation. Cancer Immunol Immunother. 2012;61(8):1233–41. Epub 2012/01/17. doi: 10.1007/s00262-011-1168-2 22249775.

12. Kohei N, Hirai T, Omoto K, Ishida H, Tanabe K. Chronic antibody-mediated rejection is reduced by targeting B-cell immunity during an introductory period. Am J Transplant. 2012;12(2):469–76. Epub 2011/11/04. doi: 10.1111/j.1600-6143.2011.03830.x 22054413.

13. Zhang R. Donor-Specific Antibodies in Kidney Transplant Recipients. Clin J Am Soc Nephrol. 2017. Epub 2017/04/26. doi: 10.2215/CJN.00700117 28446536.

14. Castro A, Malheiro J, Tafulo S, Dias L, Martins LS, Fonseca I et al. Role of de novo donor-specific anti-HLA antibodies in kidney graft failure: A case-control study. HLA. 2017;90(5):267–75. Epub 2017/08/24. doi: 10.1111/tan.13111 28776960.

15. Heilman RL, Nijim A, Desmarteau YM, Khamash H, Pando MJ, Smith ML et al. De novo donor-specific human leukocyte antigen antibodies early after kidney transplantation. Transplantation. 2014;98(12):1310–5. doi: 10.1097/TP.0000000000000216 24879384.

16. Wiebe C, Gibson IW, Blydt-Hansen TD, Pochinco D, Birk PE, Ho J et al. Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody. Am J Transplant. 2015;15(11):2921–30. Epub 2015/06/10. doi: 10.1111/ajt.13347 26096305.

17. Yamamoto T, Watarai Y, Takeda A, Tsujita M, Hiramitsu T, Goto N et al. De Novo Anti-HLA DSA Characteristics and Subclinical Antibody-Mediated Kidney Allograft Injury. Transplantation. 2016;100(10):2194–202. doi: 10.1097/TP.0000000000001012 26636737.

18. Lefaucheur C, Loupy A, Hill GS, Andrade J, Nochy D, Antoine C et al. Preexisting donor-specific HLA antibodies predict outcome in kidney transplantation. J Am Soc Nephrol. 2010;21(8):1398–406. Epub 2010/07/15. doi: 10.1681/ASN.2009101065 20634297.

19. Tydén G, Genberg H, Tollemar J, Ekberg H, Persson NH, Tufveson G et al. A randomized, doubleblind, placebo-controlled, study of single-dose rituximab as induction in renal transplantation. Transplantation. 2009;87(9):1325–9. doi: 10.1097/TP.0b013e3181a235fd 19424032.

20. Tydén G, Ekberg H, Tufveson G, Mjörnstedt L. A randomized, double-blind, placebo-controlled study of single dose rituximab as induction in renal transplantation: a 3-year follow-up. Transplantation. 2012;94(3):e21–2. doi: 10.1097/01.tp.0000418580.88642.e1 22872297.

21. van den Hoogen MW, Kamburova EG, Baas MC, Steenbergen EJ, Florquin S M Koenen HJ et al. Rituximab as induction therapy after renal transplantation: a randomized, double-blind, placebo-controlled study of efficacy and safety. Am J Transplant. 2015;15(2):407–16. doi: 10.1111/ajt.13052 25612493.

22. Loupy A, Haas M, Solez K, Racusen L, Glotz D, Seron D et al. The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology. Am J Transplant. 2017;17(1):28–41. doi: 10.1111/ajt.14107 27862883.

23. Cherkassky L, Lanning M, Lalli PN, Czerr J, Siegel H, Danziger-Isakov L et al. Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker. Am J Transplant. 2011;11(7):1388–96. Epub 2011/05/12. doi: 10.1111/j.1600-6143.2011.03540.x 21564525.

24. Webster AC, Ruster LP, McGee R, Matheson SL, Higgins GY, Willis NS et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev. 2010;(1):CD003897. Epub 2010/01/20. doi: 10.1002/14651858.CD003897.pub3 20091551.

25. Szczech LA, Berlin JA, Aradhye S, Grossman RA, Feldman HI. Effect of anti-lymphocyte induction therapy on renal allograft survival: a meta-analysis. J Am Soc Nephrol. 1997;8(11):1771–7. 9355081.

26. Tomita Y, Tojimbara T, Iwadoh K, Nakajima I, Fuchinoue S. Outcomes of Kidney Transplantation from Circulatory Death Donors With Increased Terminal Creatinine Levels in Serum. Transplantation. 2016;100(7):1532–40. doi: 10.1097/TP.0000000000000955 26479288.

27. Tomita Y, Iwadoh K, Ogawa Y, Miki K, Kai K, Sannomiya A et al. Single Graft utilization From Donors With Severe Acute Kidney Injury After Circulatory Death. Transplant Direct. 2018;4(4):e355. Epub 2018/03/19. doi: 10.1097/TXD.0000000000000768 29707626.

28. Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant. 2004;4(3):438–43. 14961999.

29. Takagi T, Ishida H, Shirakawa H, Shimizu T, Tanabe K. Evaluation of low-dose rituximab induction therapy in living related kidney transplantation. Transplantation. 2010;89(12):1466–70. doi: 10.1097/TP.0b013e3181dc0999 20559108.

30. D’Addio F, Boenisch O, Magee CN, Yeung MY, Yuan X, Mfarrej B et al. Prolonged, low-dose anti-thymocyte globulin, combined with CTLA4-Ig, promotes engraftment in a stringent transplant model. PLoS One. 2013;8(1):e53797. Epub 2013/01/10. doi: 10.1371/journal.pone.0053797 23326509.

31. Carvello M, Petrelli A, Vergani A, Lee KM, Tezza S, Chin M et al. Inotuzumab ozogamicin murine analog-mediated B-cell depletion reduces anti-islet allo- and autoimmune responses. Diabetes. 2012;61(1):155–65. Epub 2011/11/10. doi: 10.2337/db11-0684 22076927.

32. Schröder C, Azimzadeh AM, Wu G, Price JO, Atkinson JB, Pierson RN. Anti-CD20 treatment depletes B-cells in blood and lymphatic tissue of cynomolgus monkeys. Transpl Immunol. 2003;12(1):19–28. doi: 10.1016/S0966-3274(03)00059-5 14551029.

33. Kamburova EG, Koenen HJ, van den Hoogen MW, Baas MC, Joosten I, Hilbrands LB. Longitudinal analysis of T and B cell phenotype and function in renal transplant recipients with or without rituximab induction therapy. PLoS One. 2014;9(11):e112658. Epub 2014/11/13. doi: 10.1371/journal.pone.0112658 25393622.

34. Agarwal A, Vieira CA, Book BK, Sidner RA, Fineberg NS, Pescovitz MD. Rituximab, anti-CD20, induces in vivo cytokine release but does not impair ex vivo T-cell responses. Am J Transplant. 2004;4(8):1357–60. doi: 10.1111/j.1600-6143.2004.00502.x 15268740.

35. Joosten I, Baas MC, Kamburova EG, van den Hoogen MW, Koenen HJ, Hilbrands LB. Anti-B cell therapy with rituximab as induction therapy in renal transplantation. Transpl Immunol. 2014;31(4):207–9. Epub 2014/09/28. doi: 10.1016/j.trim.2014.09.011 25270152.

36. van den Hoogen MW, Steenbergen EJ, Baas MC, Florquin S, Hilbrands LB. Absence of Intragraft B Cells in Rejection Biopsies After Rituximab Induction Therapy: Consequences for Clinical Outcome. Transplant Direct. 2017;3(4):e143. Epub 2017/03/10. doi: 10.1097/TXD.0000000000000659 28405599.

37. Kamar N, Milioto O, Puissant-Lubrano B, Esposito L, Pierre MC, Mohamed AO et al. Incidence and predictive factors for infectious disease after rituximab therapy in kidney-transplant patients. Am J Transplant. 2010;10(1):89–98. Epub 2009/07/28. doi: 10.1111/j.1600-6143.2009.02785.x 19656128.

38. Kyaw T, Tay C, Krishnamurthi S, Kanellakis P, Agrotis A, Tipping P et al. B1a B lymphocytes are atheroprotective by secreting natural IgM that increases IgM deposits and reduces necrotic cores in atherosclerotic lesions. Circ Res. 2011;109(8):830–40. Epub 2011/08/25. doi: 10.1161/CIRCRESAHA.111.248542 21868694.


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