An understanding of the evaluation of histocompatibility testing for a deceased-donor transplant

Abstract

Dear Editor, Several obstacles have been overcome in the recent decades to make organ transplantation an effective lifesaving treatment for many patients. However, there is a tremendous disparity between the demand for organs and the number of organs necessary around the world, which is regarded as one of the major barriers, and India is not an exception.[1] Since 2013, the rate of deceased-donor organ donation increased from 0.27 per million people (pmp) to 0.65 pmp in 2018. Whereas the rate of deceased-donor renal transplant increased from 0.43 pmp to 0.86 pmp during the same period; this is roughly a 2.4-fold increase in just 5 years.,[2] Still, a lot of support and awareness for deceased-donor organ transplant programs is needed to help patients who do not have living kidney donors. There are numerous obstacles to overcome, with persuading family members being one of the most significant. Furthermore, transportation and allocation of the cadaver are also other issues associated with deceased-donor transplants. Once a cadaver is available, a set of histocompatibility testing of the potential patients is performed to determine the transplant’s suitability. Hence, a transplant immunology laboratory’s ability to accurately report the compatibility tests (to evaluate preformed human leukocyte antigen [HLA] donor-specific antibodies) on time is critical to the success of a deceased-donor transplant program. We want to emphasize the importance of histocompatibility testing evaluation in deceased-donor transplant programs. To support the deceased-donor transplant program, the laboratory must set up an efficient operational system to determine what kind of tests will be needed before, during, and after the transplant. In addition, a functioning 24-h on-call system should be in place. So far, a standalone transplant focused laboratory in North India, accredited for ISO15189: 2012, has aided pretransplant testing workup for 62 cadaveric cases (between February 2015 and December 2022) by optimizing the appropriate and effective test for anti-HLA antibodies between complement-dependent cytotoxicity (CDC) crossmatch, flow cytometric crossmatch (FCXM), and Luminex crossmatch.Both the CDC and the FCXM are time-consuming and labor-intensive, with the potential of false results, especially in the case of deceased donations where there is no time to redo the tests. Even technological advancements have contributed to a better understanding of transplant immunology in the recent years. In the identification of HLA antibodies, the advent of Luminex cross-matching technology provides more sensitivity than CDC and FCXM. Furthermore, unlike Luminex crossmatch, CDC and FCXM are manually created assays that require manual interpretation and whose processing method varies between laboratories. Furthermore, they (CDC and FCXM) both require a high number of viable lymphocytes to complete the experiment, whereas Luminex crossmatch requires a cell lysate to process. It is difficult to isolate a high number of viable lymphocytes from a cadaver; hence, cell count is a major concern in the cadaver transplant workup. The outcome may be harmed as a result of sample quality difficulties. Due to the aforementioned constraints, these approaches are less reliable during cadaver workup, and they also take a longer time than Luminex crossmatch. Even lysate can be saved for posttransplant monitoring.[3,4] Mishra et al. also support the findings of the use of Luminex crossmatch for pretransplant workup of renal transplants.[4] Later on, data published by Mathur et al. on 342 patients supported the usefulness of Luminex lysate crossmatch in deceased donor pretransplant workup.[3] Further, some more published literature[5,6] supports these findings; hence, Luminex crossmatch (lysate) should be used as the primary compatibility investigation for deceased-donor transplants. At present, no specific pretransplant compatibility workup for deceased-donor transplants is available. In routine practice, broadly, the pretransplant compatibility workup falls into two broad categories; cell-based tests (CDC and FCXM) and HLA bead-based (solid phase) tests (such as anti-HLA antibody screening and ant-HLA antibody identification). Laboratories typically utilize testing algorithms for compatibility, which are combinations of two or more tests, since no single test, whether cell-based or HLA bead-based, is 100% accurate and sensitive. To make donor lysate Luminex crossmatch a consensus technique, transplant physicians can be taught about the benefits. Recently, some pretransplant compatibility testing algorithm in the Indian setup is published,[7,8] which necessitates the development of one for better organ transplant outcomes, particularly in cadaver instances where there are numerous hurdles (both clinical and nonclinical). For deceased donor workup, expert analysis in a quicker turnaround time is critical, and hence, the laboratory should be equipped with cutting-edge advanced histocompatibility equipment to aid in the evaluation of histocompatibility testing for deceased-donor transplants. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.