The effect of cross-reactive epitope group matching on allocation and sensitization
The effect of cross-reactive epitope group matching on allocation and sensitization
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DOI：
10.1034/j.1399-0012.17.s9.2.x
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发表时间：
2003-01-01
影响因子：
2.1
通讯作者：
Crowe, DO
中科院分区：
文献类型：
--
作者：
Crowe, DO
HLA分子上的一些多态性是由不同的HLA类型共享的，这使我们能够根据共享的表位将HLA分子分组为“家族”或组。这些交叉反应性表位组（creg）可以作为肾移植供体与受体匹配的基础。目前的分配系统采用HLA- b、DR错配来分配HLA点。使用较新的免疫抑制药物的移植存活仍然显示0错配供者的移植存活显著改善（3年生存率约为90%），而5和6，hla错配供者的移植存活明显较差（3年生存率约为75%）。然而，1-、2-、3-和4-错配供体之间的移植物存活率差异没有显著差异（3年生存率为80-85%）。这导致了对UNOS分配系统的重新评估，并需要重新评估HLA在移植物存活、少数分配和HLA致敏中的作用。当前算法的一个问题是，很少有接受者得到匹配良好的肾脏（大约3%的人得到1个不匹配，10%的人得到2个不匹配）。移植中心使用UNOS GREG方差（0个CREG， 0个DR错配得10分）能够以比0个BDR错配高6倍的比率找到匹配。列表的大小影响找到一个好的匹配的可能性，GREG变异在更大的移植项目中更成功。HLA对肾脏公平分配的影响也正在研究中。有人担心HLA点可能至少是非洲裔美国人移植率下降的部分原因。1999年UNOS的数据显示，46.9%的移植患者是白种人，而55.2%的移植患者是白种人。相反，非裔美国人占35.8%，只有27%的移植给了非裔美国人。由于大部分献血者是白人（75.9%对11.2%），因此有人推测，黑人获得HLA积分的机会较少，因此处于不利地位。HLA对移植率的影响仍然存在争议，可能不是一个主要因素，因为很少有受者真正受益于BDR不匹配的分数。然而，CREG匹配具有平衡HLA效应的优势，因为罕见的HLA抗原与共享相同公共表位的常见HLA抗原分组。CREG匹配的另一个优势是防止HLA致敏。的。HLA配型对致敏作用随配型的增加而增强。在相同的不匹配水平下，黑人接受者比白种人更容易敏感。此外，一旦被敏感化，黑人受体接受移植的可能性比白人低，因为找到匹配良好的供体更困难。在0个creg错配供体移植的患者中，82%的患者对1类不敏感，而在2个以上bdr错配的患者中，这一比例不到60%。在肾脏分配中使用CREG配型可以为更大的受者群体提供更好的配型，并显著降低对HLA的敏感性。
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 GREG 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 GREG 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 1, 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.