|Year : 2021 | Volume
| Issue : 4 | Page : 292-294
Choosing the appropriate immunological barrier in kidney transplantation
Praveen Kumar Etta
Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad, Telangana, India
|Date of Submission||19-Oct-2020|
|Date of Decision||08-Jan-2021|
|Date of Acceptance||10-Feb-2021|
|Date of Web Publication||30-Dec-2021|
Dr. Praveen Kumar Etta
Department of Nephrology and Renal Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad - 500 034, Telangana
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Etta PK. Choosing the appropriate immunological barrier in kidney transplantation. Indian J Transplant 2021;15:292-4
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. 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. 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].
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. 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. Various desensitization protocols can lead to a successful ABOi transplant with graft survival equal to that of ABO compatible pair. 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., Choosing the appropriate immunological barrier and donor against whom the recipient is minimally sensitized is extremely important for a successful long-term graft survival.
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. 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. 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.
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