Division of Transplantation Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Transpl Immunol. 2011 Apr 15;24(3):164-71. doi: 10.1016/j.trim.2010.12.003. Epub 2010 Dec 24.
Although HLA-C matching is not considered in kidney transplantation, several reports have shown that anti-HLA-C antibodies are associated with rejection and graft failure. DNA-based typing methods can now accurately determine HLA-C compatibility and sensitive assays such as Luminex with single alleles can identify HLA-C antibodies. HLA-C displays considerable amino acid polymorphism that can be translated into a structurally defined epitope repertoire.
We have analyzed post-allograft nephrectomy sera from 45 HLA-C mismatched cases submitted by 15 laboratories worldwide participating in the 15th International Histocompatibility Workshop. All of them had HLA class I antibodies detected by a Luminex-based solid phase method using single-allele beads. This study addressed the determination of antibodies against donor HLA-C mismatches. Analysis of antibody reactivity patterns was performed using HLAMatchmaker, a structurally based matching program that considers 56 HLA-C eplets to define antibody-reactive epitopes. Many eplets shared by groups of HLA-C antigens, whereas others are also shared with HLA-A and/or HLA-B antigens.
Twenty-seven patients (60%) had donor-specific HLA-C antibodies, significantly less than the donor-specific antibodies induced by HLA-A and HLA-B mismatches. HLA-C antibody responses correlated with the eplet loads of the HLA-C mismatches. There were 352 instances whereby a donor HLA-C eplet was mismatched and for 84 (24%) of them there was antibody reactivity with a particular eplet (69 instances) or an eplet pair (15 instances). The latter generally consisted of mismatched eplets paired with self-eplets shared between the immunizing HLA-C alleles and HLA alleles of the patient. Several HLA-C eplets exhibited a relatively high immunogenicity as evidenced by their frequencies of specific antibodies.
These findings demonstrate the importance of HLA-C mismatching in humoral sensitization and that HLA-C epitopes can induce specific antibodies. They illustrate the usefulness of HLAMatchmaker in understanding donor-specific antibody reactivity patterns and the determination of HLA mismatch acceptability when transplantation is considered.
尽管在肾移植中不考虑 HLA-C 匹配，但有几项报告表明，抗 HLA-C 抗体与排斥和移植物衰竭有关。基于 DNA 的分型方法现在可以准确确定 HLA-C 相容性，而敏感的检测方法（如带有单等位基因的 Luminex）可以识别 HLA-C 抗体。HLA-C 显示出相当大的氨基酸多态性，可以转化为结构定义的表位库。
我们分析了来自全球 15 个实验室的 45 例 HLA-C 错配病例的移植后肾切除术后血清，这些实验室参加了第 15 届国际组织相容性研讨会。所有病例均通过基于 Luminex 的固相方法使用单等位基因珠检测到 HLA Ⅰ类抗体。本研究旨在确定针对供体 HLA-C 错配的抗体。使用 HLAMatchmaker 分析抗体反应模式，这是一种基于结构的匹配程序，考虑了 56 个 HLA-C 表位来定义抗体反应性表位。许多 HLA-C 抗原组共享的表位，而其他表位也与 HLA-A 和/或 HLA-B 抗原共享。
27 例（60%）患者存在供体特异性 HLA-C 抗体，明显少于 HLA-A 和 HLA-B 错配诱导的供体特异性抗体。HLA-C 抗体反应与 HLA-C 错配的表位负荷相关。有 352 个 HLA-C 表位错配，其中 84 个（24%）有特定表位（69 个实例）或表位对（15 个实例）的反应。后者通常由错配的表位与免疫 HLA-C 等位基因和患者 HLA 等位基因之间共享的自身表位配对组成。一些 HLA-C 表位显示出相对较高的免疫原性，这表明它们具有特定抗体的频率。
这些发现表明 HLA-C 错配在体液致敏中的重要性，以及 HLA-C 表位可以诱导特异性抗体。它们说明了 HLAMatchmaker 在理解供体特异性抗体反应模式和确定移植时 HLA 错配可接受性方面的有用性。
