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Table of Contents
EDITORIAL
Year : 2021  |  Volume : 15  |  Issue : 4  |  Page : 292-294

Choosing the appropriate immunological barrier in kidney transplantation


Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad, Telangana, India

Date of Submission19-Oct-2020
Date of Decision08-Jan-2021
Date of Acceptance10-Feb-2021
Date of Web Publication30-Dec-2021

Correspondence Address:
Dr. Praveen Kumar Etta
Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad - 500 034, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_119_21

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How to cite this article:
Etta PK. Choosing the appropriate immunological barrier in kidney transplantation. Indian J Transplant 2021;15:292-4

How to cite this URL:
Etta PK. Choosing the appropriate immunological barrier in kidney transplantation. Indian J Transplant [serial online] 2021 [cited 2022 Jul 4];15:292-4. Available from: https://www.ijtonline.in/text.asp?2021/15/4/292/334297



The genetic disparities between transplant candidate and donor may provoke alloimmune response, which remains an important barrier to the long-term graft survival in kidney transplantation (KT). The advances in histocompatibility evaluation with various tools such as high-resolution human leukocyte antigen (HLA) typing and assessing its matching, performing cross-match (XM) tests (complement dependent cytotoxicity [CDC-XM] and flow cytometry XM [FCXM]), identification of unacceptable HLA antigens and donor-specific anti-HLA antibodies (HLA-DSA) on solid-phase immunoassays (virtual XM), and testing for panel reactive antibodies (PRA) have immensely helped physicians in understanding transplant immunology and improved the safety of KT with reduced incidence of rejections.[1] The various tools guide in risk stratification, prognostication, to decide on transplant eligibility, selection of immunologically favorable donor, to plan desensitization and immunosuppression including induction therapy.[2] Currently, no single assay is capable of capturing all aspects of alloreactive cellular and humoral immune responses. Therefore, combinations of different assays in addition to conventional tests should be used to have a complete picture of the alloimmune response. For best transplant outcomes, a complete immunological workup and an in-depth understanding of these tests are important for choosing the most suitable donor against whom the recipient is least sensitized [Table 1].
Table 1: Interpretation of immunological tests in kidney transplanta

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About half of the potential donors get rejected due to various immunological barriers. The major barriers in relation to KT include anti-HLA antibodies (HLA incompatibility [HLAi]), anti-A/B antibodies (blood group or ABO incompatibility [ABOi]), and non-HLA antibodies.[3] The various management options in these cases include (a) proceeding with transplantation after desensitization of recipient, (b) choosing alternate live compatible donor either within the family or by kidney paired donation (KPD) program, and (c) waitlisting in deceased donor program for a compatible donor. Highly sensitized end-stage kidney disease (ESKD) patients or those with blood group O tend to accumulate on the deceased donor as well as KPD waitlist. Many a time, it is necessary to proceed with desensitization as other options are not always feasible. In many centers, persistent CDC-XM positivity (especially with T-cells) is considered as an absolute contraindication to proceed with transplantation. Most of the cases with FCXM positivity with negative CDC-XM and/or low-level HLA-DSA can undergo desensitization successfully. The aim of desensitization therapies is to reduce the level of circulating preformed antidonor antibody titers below a safe threshold level as higher titers are associated with antibody-mediated rejection (ABMR) posttransplant.[4] Various desensitization protocols can lead to a successful ABOi transplant with graft survival equal to that of ABO compatible pair.[5] In contrast, HLAi barrier is less amenable to desensitization, with higher risk of ABMR and poor long-term graft survival, though the longevity and quality of life of desensitized patients is better than those remaining on dialysis and waitlist.[6],[7] Choosing the appropriate immunological barrier and donor against whom the recipient is minimally sensitized is extremely important for a successful long-term graft survival.[8]

In a case report, Jha et al. had to choose one among several donors with immunological barriers for a highly sensitized young female with ESKD and very high PRA level. Her father was rejected as donor due to CDC-XM positivity. With her maternal aunt (5/6 HLA mismatch), FCXM for both T and B cells was positive with high titer class I and II HLA-DSA on Luminex single-antigen bead assay, hence she was also rejected. There were no other ABO-compatible donors available in her family. Her mother, though ABOi donor, was selected due to better HLA match (2/6 mismatch), and the recipient had only low titer class II HLA-DSA alone against her mother. KT was performed successfully with her mother as donor after desensitization of the recipient. The authors have concluded that HLAi is the most important and clinically significant barrier than ABOi barrier.[9] This has also been concluded in a recent nationwide cohort study by the Korean Organ Transplantation Registry Study Group, where the authors observed a higher incidence of rejection in the HLAi and ABOi + HLAi groups compared to the control group of compatible transplants and ABOi group. Authors concluded that HLA incompatibility was more important risk factor for rejection than ABO incompatibility.[10] These findings highlight the fact that HLAi rather than ABOi should be the deciding factor in choosing an appropriate donor. In other words, least HLAi donor or highest HLA-matched donor should be given priority for organ donation.

To conclude, careful selection of immunologically favorable donor against whom the recipient is least sensitized after thorough histocompatibility testing and immunological evaluation is important when transplanting highly sensitized candidates. HLAi rather than ABOi should be the deciding factor in choosing an appropriate donor. The desensitized recipients need close follow-up and posttransplant monitoring with regular HLA-DSA measurements and protocol biopsies as per center's choice.



 
  References Top

1.
Tait BD, Süsal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation 2013;95:19-47.  Back to cited text no. 1
    
2.
Etta PK. Testing for donor-specific antibodies in renal transplantation: Indian perspective. Indian J Transplant 2020;14:90-3.  Back to cited text no. 2
  [Full text]  
3.
Etta PK. Thrombotic microangiopathy and rejection in blood group incompatible renal transplantation. Indian J Transplant 2020;14:5-7.  Back to cited text no. 3
  [Full text]  
4.
Etta PK, Rao MV. Renal allograft dysfunction: An update on immunological graft injury. Indian J Transplant 2019;13:69-77.  Back to cited text no. 4
  [Full text]  
5.
de Weerd AE, Betjes MGH. ABO-Incompatible Kidney Transplant Outcomes: A Meta-Analysis. Clin J Am Soc Nephrol 2018;13:1234-43.  Back to cited text no. 5
    
6.
Marfo K, Lu A, Ling M, Akalin E. Desensitization protocols and their outcome. Clin J Am Soc Nephrol 2011;6:922-36.  Back to cited text no. 6
    
7.
Montgomery RA, Lonze BE, King KE, Kraus ES, Kucirka LM, Locke JE, et al. Desensitization in HLA-incompatible kidney recipients and survival. N Engl J Med 2011;365:318-26.  Back to cited text no. 7
    
8.
Etta PK. C4d staining and antibody mediated rejection in renal transplantation: Current status. Indian J Transplant 2020;14:197-201.  Back to cited text no. 8
  [Full text]  
9.
Jha PK, Kher A, Kher V. A case report of ABO and human leukocyte antigen incompatible renal transplant – Being immunologically smart. Indian J Transplant 2020;14:346-8.  Back to cited text no. 9
  [Full text]  
10.
Ko EJ, Yu JH, Yang CW, Chung BH, Korean Organ Transplantation Registry Study Group. Clinical outcomes of ABO- and HLA-incompatible kidney transplantation: A nationwide cohort study. Transpl Int 2017;30:1215-25.  Back to cited text no. 10
    



 
 
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