What Do Donor-Specific Antibody Changes Mean in Kidney Transplant Patients?

Year 2023, Volume: 5 Issue: 4, 216 - 223, 29.10.2023

Talat Aykut , Hakan Ozer , İsmail Baloğlu , Fatih Saçkan , Kültigin Türkmen

https://doi.org/10.46310/tjim.1249847

Abstract

Objective: The role of immunological evaluation is significant in selecting a suitable donor to reduce post-transplant complications in kidney transplantation (KTx). It is unknown how often donor-specific antibody (DSA) positivity causes rejection or how often rejection will develop in patients who do not develop DSA positivity. We aimed to evaluate the relationship between the DSA changes and the KTx patients' biochemical parameters.
Methods: The study was a cross-sectional study evaluating 45 KTx patients. Demographic and clinical characteristics of the patients, pre-transplant DSA values, post-transplant DSA values, and biochemical parameters were retrospectively scanned from the hospital system. The patients' data were divided into three groups according to DSA changes.
Results: DSA was negative in 21 (46%) patients and positive in 24 (54%) before transplantation. In the post-transplant follow-up, it was observed that the DSA value became positive in 7 patients and turned negative in 9 patients. Rejection developed in 22% of 9 patients whose DSA was positive before transplantation and turned negative after transplantation, and in 28% of 7 patients turned positive from negative. Estimated glomerular filtration rate (e-GFR) and creatinine levels in the post-transplant period were associated with the change in DSA. Also, e-GFR and neutrophil values were independently associated with rejection.
Conclusions: Although DSA change affects kidney functions, we found that DSA positivity alone cannot predict rejection, and rejection may occur in the DSA-negative group. Neutrophil count and e-GFR changes were closely related to rejection. Therefore, DSA levels should be monitored regularly, but DSA change alone is insufficient for rejection evaluation.

Keywords

Donor spesific antibody, graft rejection, kidney transplantation

References

• Bagnasco SM, Zachary AA, Racusen LC, Arend LJ, Carter-Monroe N, Alachkar N, Nazarian SM, Lonze BE, Montgomery RA, Kraus ES. Time course of pathologic changes in kidney allografts of positive crossmatch HLA-incompatible transplant recipients. Transplantation. 2014 Feb 27;97(4):440-5. doi: 10.1097/01.TP.0000437177.40551.f4.
• Rabbat CG, Thorpe KE, Russell JD, Churchill DN. Comparison of mortality risk for dialysis patients and cadaveric first renal transplant recipients in Ontario, Canada. J Am Soc Nephrol. 2000 May;11(5):917-22. doi: 10.1681/ASN.V115917.
• Abecassis M, Bartlett ST, Collins AJ, Davis CL, Delmonico FL, Friedewald JJ, Hays R, Howard A, Jones E, Leichtman AB, Merion RM, Metzger RA, Pradel F, Schweitzer EJ, Velez RL, Gaston RS. Kidney transplantation as primary therapy for end-stage renal disease: a National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQITM) conference. Clin J Am Soc Nephrol. 2008 Mar;3(2):471-80. doi: 10.2215/CJN.05021107.
• Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG, Kaplan B, Halloran PF. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant. 2009 Nov;9(11):2520-31. doi: 10.1111/j.1600-6143.2009.02799.x.
• Terasaki PI, Cai J. Human leukocyte antigen antibodies and chronic rejection: from association to causation. Transplantation. 2008 Aug 15;86(3):377-83. doi: 10.1097/TP.0b013e31817c4cb8.
• Zhang Q, Liang LW, Gjertson DW, Lassman C, Wilkinson AH, Kendrick E, Pham PT, Danovitch GM, Gritsch HA, Reed EF. Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction. Transplantation. 2005 Mar 15;79(5):591-8. doi: 10.1097/01.tp.0000155246.52249.ac.
• McKenna RM, Takemoto SK, Terasaki PI. Anti-HLA antibodies after solid organ transplantation. Transplantation. 2000 Feb 15;69(3):319-26. doi: 10.1097/00007890-200002150-00001.
• Fernández-Fresnedo G, Pastor JM, López-Hoyos M, Ruiz JC, Zubimendi JA, Gonzalez-Cotorruelo J, Rodrigo E, De Francisco AL, Arias M. Relationship of donor-specific class-I anti-HLA antibodies detected by ELISA after kidney transplantation on the development of acute rejection and graft survival. Nephrol Dial Transplant. 2003 May;18(5):990-5. doi: 10.1093/ndt/gfg068.
• Walsh RC, Brailey P, Girnita A, Alloway RR, Shields AR, Wall GE, Sadaka BH, Cardi M, Tevar A, Govil A, Mogilishetty G, Roy-Chaudhury P, Woodle ES. Early and late acute antibody-mediated rejection differ immunologically and in response to proteasome inhibition. Transplantation. 2011 Jun 15;91(11):1218-26. doi: 10.1097/TP.0b013e318218e901.
• Orandi BJ, Chow EH, Hsu A, Gupta N, Van Arendonk KJ, Garonzik-Wang JM, Montgomery JR, Wickliffe C, Lonze BE, Bagnasco SM, Alachkar N, Kraus ES, Jackson AM, Montgomery RA, Segev DL. Quantifying renal allograft loss following early antibody-mediated rejection. Am J Transplant. 2015 Feb;15(2):489-98. doi: 10.1111/ajt.12982.
• Aubert O, Loupy A, Hidalgo L, Duong van Huyen JP, Higgins S, Viglietti D, Jouven X, Glotz D, Legendre C, Lefaucheur C, Halloran PF. Antibody-mediated rejection due to preexisting versus de novo donor-specific antibodies in kidney allograft recipients. J Am Soc Nephrol. 2017 Jun;28(6):1912-1923. doi: 10.1681/ASN.2016070797.
• Mittal KK, Mickey MR, Singal DP, Terasaki PI. Serotyping for homotransplantation. 18. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation. 1968 Nov;6(8):913-27. doi: 10.1097/00007890-196811000-00006.
• Jeannet M, Pinn VW, Flax MH, Winn HJ, Russell PS. Humoral antibodies in renal allotransplantation in man. N Engl J Med. 1970 Jan 15;282(3):111-7. doi: 10.1056/NEJM197001152820301.
• Terasaki PI. Humoral theory of transplantation. Am J Transplant. 2003 Jun;3(6):665-73. doi: 10.1034/j.1600-6143.2003.00135.x.
• Heilman RL, Nijim A, Desmarteau YM, Khamash H, Pando MJ, Smith ML, Chakkera HA, Huskey J, Valdez R, Reddy KS. De novo donor-specific human leukocyte antigen antibodies early after kidney transplantation. Transplantation. 2014 Dec 27;98(12):1310-5. doi: 10.1097/TP.0000000000000216.
• Kaufman A, de Souza Pontes LF, Queiroz Marques MT, Sampaio JC, de Moraes Sobrino Porto LC, de Moraes Souza ER. Analysis of AHG-PRA and ELISA-PRA in kidney transplant patients with acute rejection episodes. Transpl Immunol. 2003 Apr-Jun;11(2):175-8. doi: 10.1016/s0966-3274(03)00003-0.
• Pelletier RP, Hennessy PK, Adams PW, VanBuskirk AM, Ferguson RM, Orosz CG. Clinical significance of MHC-reactive alloantibodies that develop after kidney or kidney-pancreas transplantation. Am J Transplant. 2002 Feb;2(2):134-41. doi: 10.1034/j.1600-6143.2002.020204.x.
• Panigrahi A, Deka R, Bhowmik D, Tiwari SC, Mehra NK. Immunological monitoring of posttransplant allograft sensitization following living related donor renal transplantation. Transplant Proc. 2004 Jun;36(5):1336-9. doi: 10.1016/j.transproceed.2004.05.072.
• Varnavidou-Nicolaidou A, Doxiadis II, Iniotaki-Theodoraki A, Patargias T, Stavropoulos-Giokas C, Kyriakides GK. HLA class I donor-specific triplet antibodies detected after renal transplantation. Transplant Proc. 2004 Jul-Aug;36(6):1732-4. doi: 10.1016/j.transproceed.2004.06.006.
• Hourmant M, Cesbron-Gautier A, Terasaki PI, Mizutani K, Moreau A, Meurette A, Dantal J, Giral M, Blancho G, Cantarovich D, Karam G, Follea G, Soulillou JP, Bignon JD. Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation. J Am Soc Nephrol. 2005 Sep;16(9):2804-12. doi: 10.1681/ASN.2004121130.
• Crespo M, Pascual M, Tolkoff-Rubin N, Mauiyyedi S, Collins AB, Fitzpatrick D, Farrell ML, Williams WW, Delmonico FL, Cosimi AB, Colvin RB, Saidman SL. Acute humoral rejection in renal allograft recipients: I. Incidence, serology and clinical characteristics. Transplantation. 2001 Mar 15;71(5):652-8. doi: 10.1097/00007890-200103150-00013.
• Yell M, Muth BL, Kaufman DB, Djamali A, Ellis TM. C1q binding activity of de novo donor-specific HLA antibodies in renal transplant recipients with and without antibody-mediated rejection. Transplantation. 2015 Jun;99(6):1151-5. doi: 10.1097/TP.0000000000000699.
• Sumitran-Holgersson S. HLA-specific alloantibodies and renal graft outcome. Nephrol Dial Transplant. 2001 May;16(5):897-904. doi: 10.1093/ndt/16.5.897.
• Keven K, Şengül Ş, Tüzüner A, Yalçın F, Tutkak H. Renal transplantation in donor specific antibody positive sensitized patients: Single center experience. Turkish J Nephrol. 2011 Sep;20(3):255-9. doi: 10.5262/tndt.2011.1003.08.
• Mao Q, Terasaki PI, Cai J, El-Awar N, Rebellato L. Analysis of HLA class I specific antibodies in patients with failed allografts. Transplantation. 2007 Jan 15;83(1):54-61. doi: 10.1097/01.tp.0000250492.55775.83.
• El-Awar N, Terasaki P, Lazda V, Nikaein A, Manning C, Arnold AN. Almost all patients who are waiting for a regraft of a kidney transplant have anti-HLA antibodies. Transplant Proc. 2002 Nov;34(7):2531-2. doi: 10.1016/s0041-1345(02)03520-0.
• Worthington JE, Martin S, Dyer PA, Johnson RW. An association between posttransplant antibody production and renal transplant rejection. Transplant Proc. 2001 Feb-Mar;33(1-2):475-6. doi: 10.1016/s0041-1345(00)02099-6.
• Zou Y, Mirbaha F, Lazaro A, Zhang Y, Lavingia B, Stastny P. MICA is a target for complement-dependent cytotoxicity with mouse monoclonal antibodies and human alloantibodies. Hum Immunol. 2002 Jan;63(1):30-9. doi: 10.1016/s0198-8859(01)00349-4.
• Halloran PF, Wadgymar A, Ritchie S, Falk J, Solez K, Srinivasa NS. The significance of the anti-class I antibody response. I. Clinical and pathologic features of anti-class I-mediated rejection. Transplantation. 1990 Jan;49(1):85-91. doi: 10.1097/00007890-199001000-00019.
• Suviolahti E, Ge S, Nast CC, Mirocha J, Karasyov A, White M, Jordan SC, Toyoda M. Transpl Immunol. 2015 Jan;32(1):9-17. doi: 10.1016/j.trim.2014.11.215. Genes associated with antibody-dependent cell activation are overexpressed in renal biopsies from patients with antibody-mediated rejection.
• Hidalgo LG, Campbell PM, Sis B, Einecke G, Mengel M, Chang J, Sellares J, Reeve J, Halloran PF. De novo donor-specific antibody at the time of kidney transplant biopsy associates with microvascular pathology and late graft failure. Am J Transplant. 2009 Nov;9(11):2532-41. doi: 10.1111/j.1600-6143.2009.02800.x.