Mangiola Massimo, Ellison Mitchell, Marrari Marilyn, Xu Qingyong, Mankowski Michal, Sese Doreen, Lonze Bonnie E, Montgomery Robert A, Zeevi Adriana
NYU Langone Transplant Institute, New York, New York, USA.
University of Pittsburgh Medical Centre, Pittsburgh, Pennsylvania, USA.
HLA. 2024 Dec;104(6):e70000. doi: 10.1111/tan.70000.
The degree of immunological compatibility between donors and recipients greatly impacts allograft survival. In the United States kidney allocation system, HLA antigen-level matching has been shown to cause ethnic disparities and thus, has been de-emphasised. However, priority points are still awarded for antigen-level zero-ABDR matching, zero-DR matching and one-DR matching. Recently, the degree of HLA molecular (eplet) mismatch has emerged as a more accurate measure of immunological risk, and eplet mismatch load has gained attention as a possible biomarker to improve HLA compatibility. However, little is known about the frequency of eplets in population groups, which is a necessary step to ensure that candidates from any ethnical background can have similar chances at a well-matched organ. Eplet frequencies were estimated using HLA alleles in the Common, Intermediate and Well-Documented (CIWD) 3.0.0 catalogue for six population groups: African-American (AFA), Asian-Pacific Islander (API), European/European descent (EURO), Middle East/North Coast of Africa (MENA), Hispanic/Latino (HIS) and Native-American (NAM). We determined that 98.6% (484 out of 491) of HLA eplets are expressed by the common HLA alleles in all population groups. Of the seven eplets that were expressed by less common HLA alleles, six were Class I eplets and one was expressed by HLA-DQB1 alleles and most were expressed by HLA alleles that were more commonly observed in European/European descent populations. Our observations indicate that HLA eplets will not cause any significant disparity if applied to HLA molecular compatibility, regardless of the ethnic origin of both recipients and donors.
供体与受体之间的免疫相容性程度对同种异体移植物的存活有很大影响。在美国肾脏分配系统中,HLA抗原水平匹配已被证明会导致种族差异,因此已不再被强调。然而,抗原水平零-ABDR匹配、零-DR匹配和单-DR匹配仍会被赋予优先分数。最近,HLA分子(表位)错配程度已成为衡量免疫风险的更准确指标,表位错配负荷作为一种可能改善HLA相容性的生物标志物受到了关注。然而,关于人群中表位的频率知之甚少,而这是确保任何种族背景的候选人都有同等机会获得匹配良好器官的必要步骤。我们使用通用、中级和充分记录(CIWD)3.0.0目录中的HLA等位基因,对六个群体的表位频率进行了估计:非裔美国人(AFA)、亚太岛民(API)、欧洲/欧洲血统(EURO)、中东/北非海岸(MENA)、西班牙裔/拉丁裔(HIS)和美洲原住民(NAM)。我们确定,98.6%(491个中的484个)的HLA表位由所有群体中的常见HLA等位基因表达。在由较不常见的HLA等位基因表达的七个表位中,六个是I类表位,一个由HLA-DQB1等位基因表达,且大多数由在欧洲/欧洲血统人群中更常见的HLA等位基因表达。我们的观察结果表明,如果应用于HLA分子相容性,HLA表位不会导致任何显著差异,无论受体和供体的种族来源如何。