The effect of cross-reactive epitope group matching on allocation and sensitization.

Some polymorphisms on HLA molecules are shared by different HLA types, which allows us to group HLA molecules into 'families' or groups based on the shared epitope. These cross-reactive epitope groups (CREGs) can be used as a basis for matching donors to recipients for renal transplantation. The current allocation system uses HLA-B,DR mismatching for assigning HLA points. Graft survival using newer immunosuppressive drugs still shows a significant improvement in graft survival for 0-mismatched donors (3-year survival approximately 90%) and a significantly worse graft survival for 5 and 6 HLA-mismatched donors (3-year graft survival approximately 75%). However, the difference in graft survival between 1-, 2-, 3- and 4-mismatched donors are nor significantly different from each other (80-85% survival at 3 year). This has led to a reassessment of the UNOS allocation system and the need to re-evaluate the role of HLA in graft survival, minority allocation, and HLA sensitization. One of the problems with the current algorithm is that very few recipients are actually getting well-matched kidneys (approximately 3% get 1 mismatch and 10% get 2 mismatch). Transplant centres using the UNOS CREG variance (10 points awarded for 0 CREG, 0 DR mismatches) were able to find matches at a sixfold higher rate over 0 BDR mismatches. The size of the list affects the likelihood of finding a good match and the CREG variance was more successful in larger transplant programs. The effect of HLA on equity in renal allocation is also being addressed. There is some concern that HLA points may be at least partially responsible for the decreased transplant rate in African Americans. The 1999 UNOS data showed that 46.9% of the list were Caucasian, while 55.2% of the transplants were in Caucasian recipients. Conversely, African Americans made up 35.8% of the list and only 27% of the transplants went to African Americans. Since most of the donors were Caucasian (75.9% vs. 11.2%), it has been speculated that the Black population may be disadvantaged because they have less chance of getting HLA points. The impact of HLA on transplant rate is still being disputed and may not be a major factor since so few recipients actually benefit from the points given for BDR mismatches. However, CREG matching has the advantage of equalizing the HLA effect since rare HLA antigens are grouped with common HLA antigens sharing the same public epitopes. Another advantage for CREG matching is the protection from sensitization to HLA. The effect of HLA matching on sensitization is increased with each HLA match. Black recipients are more likely to be sensitized than Caucasians with the same level of mismatch. Also, once sensitized, Black recipients are less likely to get transplanted than Caucasians because of greater difficulty in finding a well-matched donor. Of patients transplanted with 0 CREG-mismatched donors, 82% remained unsensitized to Class I, compared with less than 60% in recipients who received greater than 2 BDR mismatches. The use of CREG matching in renal allocation offers better matching to a larger group of recipients and significantly reduces sensitization to HLA.