Posttransplant de novo donor specific HLA antibody monitoring and clinical outcomes: a single-center experience

Yıl 2021, Cilt: 7 Sayı: 3, 304 - 311, 04.05.2021

Nurettin Ay , Vahhac Alp Şeyhmus Kaya

https://doi.org/10.18621/eurj.732625

Öz

Objectives: Despite the improvements in early-term outcomes of kidney transplantation, late-term graft failure still remained as a critical problem. De novo donor specific antibodies (DSA) developing against direct human leukocyte antigens (HLA) are the significant risk factors for shortened graft survival in the previously non-sensitized cases. The purpose of this study is to evaluate the clinical outcomes of de novo DSA development in the kidney transplant cases.

Methods: The present study included 121 (alive/cadaver: 106/15) of 148 (alive/cadaver: 125/23) cases who were not previously sensitized (PRA and DSA negative) and undergone kidney transplantation between August 2012-January 2018. DSAs of the cases without expected declines in creatinine levels in the polyclinic follow-ups and postoperative early-term were evaluated. Renal biopsy was performed in the cases encountered with >2000 mean fluorescence intensity (MFI) de novo DSA against HLA-A, HLA-B, HLA-DR. Treatment protocol of plasmapheresis+intravenous immunoglobulin (IVIG)+rituximab (in the cases without clinical response) was administered in the cases with antibody-mediated rejection (AMR) detected by renal biopsy. In addition, the presence of de novo non-DSA was also evaluated in the cases. The presence of de novo was encountered by identifying the specificities of anti-HLA antibody specificities using Luminex single antigen beads in the recipient serum.

Results: De novo DSA (antibodies against HLA-A, HLA-B, HLA-DR and HLA-DQ) were monitored in 23 cases. DQ positivity was detected in 10 cases. MFI values were > 4000 and 2000-4000 in 8 and 2 cases, respectively. De novo non-DSA was found in 19 cases. Biopsy was performed in 8 cases due to the development of MFI > 2000 de novo DSA against HLA-A, HLA-B and HLA-DR and the findings of acute humoral rejection (AHR) were encountered in 2 cases. Additionally, acute humoral rejection was diagnosed in 1 case that developed de novo non-DSA. Two cases were diagnosed with AHR by biopsy although no de novo DSA or non-DSA developed and renal graft loss occurred in these two cases.

Conclusions: The fact that routine DSA monitoring in all the cases provided no significant contribution to the outcomes of our study may contribute to the debates on the necessity of DSA monitoring in the patients with low immunological risk.

Anahtar Kelimeler

de novo DSA, kidney, transplantation, monitoring

Kaynakça

• 1. Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 2004;4:1289-95.
• 2. Morath C, Opelz G, Zeier M, Süsal C. Clinical relevance of HLA antibody monitoring after kidney transplantation. J Immunol Res 2014;2014:845040.
• 3. Loupy A, Hill GS, Nochy D, Legendre C. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 2010;10:952.
• 4. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012;12:388-99.
• 5. Meier-Kriesche HU, Schold JD, Srinivas TR, Kaplan B. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004;4:378-83.
• 6. Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003;3:665-73.
• 7. Lachmann N, Terasaki PI, Budde K, Liefeldt L, Kahl A, Reinke P, 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;27;87:1505-13.
• 8. Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 2009;9:2520-31.
• 9. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant 2012;12:388-99.
• 10. Li X, Ishida H, Yamaguchi Y, Tanabe K. Poor graft outcome in recipients with de novo donor-specific anti-HLA antibodies after living related kidney transplantation. Transpl Int 2008;21:1145-52.
• 11. McKenna RM, Takemoto SK, Terasaki PI. Anti-HLA antibodies after solid organ transplantation. Transplantation 2000;69:319-26.
• 12. Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant 2004;4:438-43.
• 13. Süsal C, Aykut G, Morath C, Fichtner A, Unterrainer C, Scherer S, et al. Relevance of donor-specific antibody monitoring after kidney transplantation: findings from the Collaborative Transplant Study and the Heidelberg Transplant Center. HLA 2019;94 Suppl 2:11-5.
• 14. Parajuli S, Joachim E, Alagusundaramoorthy S, Aziz F, Blazel J, Garg N, et al. Donor-specific antibodies in the absence of rejection are not a risk factor for allograft failure. Kidney Int Rep 2019;4:1057-65.
• 15. Cioni M, Nocera A, Innocente A, Tagliamacco A, Trivelli A, Basso S, et al. De novo donor-specific HLA antibodies developing early or late after transplant are associated with the same risk of graft damage and loss in nonsensitized kidney recipients. J Immunol Res 2017;2017:1747030.
• 16. Ginevri F, Nocera A, Comoli P, Innocente A, Cioni M, Parodi A, et al. Posttransplant de novo donor-specific HLA antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection. Am J Transplant 2012;12:3355-62.
• 17. Wiebe C, Gibson IW, Blydt-Hansen TD, Karpinski M, Ho J, Storsley LJ, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012;12:1157-67.
• 18. Tagliamacco A, Cioni M, Comoli P, Ramondetta M, Brambilla C, Trivelli A, et al. DQ molecules are the principal stimulators of de novo donor-specific antibodies in nonsensitized pediatric recipients receiving a first kidney transplant. Transpl Int 2014;27:667-73.
• 19. Willicombe M, Brookes P, Sergeant R, Santos-Nunez E, Steggar C, Galliford J, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation 2012;94:172-7.
• 20. DeVos JM, Gaber AO, Knight RJ, Land GA, Suki WN, Gaber LW, et al. Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after renal transplantation. Kidney Int 2012;82:598-604.
• 21. Morris GP, Phelan DL, Jendrisak MD, Mohanakumar T. Virtual cross match by identification of donor-specific anti-human leukocyte antigen antibodies by solid-phase immunoassay: a 30-month analysis in living donor kidney transplantation. Hum Immunol 2010;71:268-73.
• 22. Caro-Oleas JL, Gonza´lez-Escribano MF, Gonza´lez-Roncero FM, Acevedo-Calado MJ, Cabello-Chaves V, Gentil-Govantes MA, et al. Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation. Nephrol Dial Transplant 2012;27:1231-8.