Trends in HLA Antibody Screening and Identification and Their Role in Transplantation

Cathi L Murphey; Thomas G Forsthuber


Expert Rev Clin Immunol. 2008;4(3):391-399. 

In This Article

Calculated PRA & 'Virtual Crossmatching'

Organ allocation in the USA is comprised of complex algorithms that are based on the type of organ to be allocated and the specific needs of each cohort of patients. Current kidney allocation is based on a combination of length of time on the waiting list, HLA-DR match and PRA, with additional waiting list points being assigned for values greater than 80%. Little or no standardization of PRA levels exists between laboratories, due to the diverse methodologies currently performed by the individual HLA laboratories. Furthermore, substantiation of the high level of PRA (>80%) for additional points by assignment of unacceptable antigens was not previously required by UNOS. Another allocation issue relating to the assignment of PRAs was the fact that it was not possible to enter both HLA class I and class II PRA levels; only one level could be entered for a given patient. Not surprisingly, patients who had both HLA class I and class II antibodies that fell below the 80% mark individually, could have, potentially, combined PRA levels of greater than 80%, thereby disadvantaging this cohort of patients. These concerns were addressed by the UNOS Histocompatibility Committee and new policies were adopted, whereby PRA percentages are now calculated based on antigens that are assigned as unacceptable in the UNOS computer and the frequencies of those antigens in the donor population.[35,36] These new policies will be implemented in three phases, with Phase I implementation due to have started in September 2007.[53] The calculated PRA computes the PRA percentage using both anti-HLA class I and class II antibody specificities, assigned to each patient as unacceptable, and knowledge of the frequency of the assigned unacceptable HLA antigens in a representative population. Not surprisingly, the type of testing employed for determining antibody specificity directly affects the outcome of assignment of allocation points. For example, previously, a patient that had a HLA class I PRA of 50% and a HLA class II PRA of 60% would be entered into the UNOS computer with a PRA of either 50 or 60%. However, with the new calculated PRA, the calculated value based on the unacceptable could be greater than 80% and the patient would receive extra allocation points.

The concept of adapting strategies to transplant highly sensitized patients is hardly a new one. These types of programs, including the acceptable mismatch and hyperimmune tray program, have been in place for 20 years in Europe[37,38,39] and, more recently, in the USA,[40] and have been very efficacious in transplanting highly sensitized patients. The US and Eurotransplant strategies vary slightly, with the Eurotransplant program 'pulling' patients into the system by identifying the 'acceptable mismatches' for a patient, while the US system 'pushes' patients away from transplantation owing to assigned 'unacceptable mismatches'. Ultimately, the goal is the same: successfully transplanting highly sensitized patients.

The newer technology has added another layer of confidence in performing 'virtual crossmatching'.[40,41,42,43,44] In essence, the crossmatch outcome would be predictable based on the unacceptable HLA antigens that had been defined by these sensitive and specific technologies. The idea of implementing this 'virtual crossmatching' nationwide in the USA is very provocative. For many transplant centers, it is still standard procedure to perform 'preliminary screening trays' that screen either highly sensitized patients or all patients against every prospective donor. This is a time-consuming and costly step in the patient-donor selection process. If the final crossmatch can be accurately predicted, it will no longer be necessary to run preliminary screening trays for prospective renal patients waiting for deceased donor transplants. The effects of eliminating this step in the transplant process are multiple: it saves time for the initial donor work-up, there is a significant cost saving to the transplant center and, most importantly, it has been shown to increase access to deceased donor transplant for the highly sensitized patient, due to the added confidence and reliability of predicting crossmatch outcome.[40]


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