The detection and semiquantitative measurement of circulating human leucocyte antigen (HLA)‐specific antibodies is essential for the management of patients before and after transplantation. In addition, the pretransplant cross‐match to assess the reactivity of recipient HLA antibody against donor lymphocytes has long been the gold standard to prevent hyperacute rejection. Whilst both of these tests assume that recipient HLA‐specific antibody is the only variable in the assessment of transplant risk, this is not the case. Transplant immunologists recognize that some HLA antigens are expressed at levels a magnitude lower than others (e.g., HLA‐C, HLA‐DQ), but within loci, and between different cell types there are many factors that influence HLA expression in both resting and activated cells. HLA is not usually expressed without the specific promoter proteins NLRC5, for HLA class I, and CIITA, for class II. The quantity of HLA protein production is then affected by factors including promoter region polymorphisms, alternative exon splice sites, methylation and microRNA‐directed degradation. Different loci are influenced by multiple combinations of these control mechanisms making prediction of HLA regulation difficult, but an ability to measure the cellular expression of each HLA antigen, in conjunction with knowledge of circulating HLA‐specific antibody, would lead to a more informed algorithm to assess transplant risk.

中文翻译：

---

影响 HLA 表达的因素：综述

循环人类白细胞抗原 (HLA) 特异性抗体的检测和半定量测量对于移植前后患者的管理至关重要。此外，用于评估受体 HLA 抗体对供体淋巴细胞反应性的移植前交叉匹配长期以来一直是预防超急性排斥反应的金标准。虽然这两项测试都假设受体 HLA 特异性抗体是评估移植风险的唯一变量，但事实并非如此。移植免疫学家认识到，一些 HLA 抗原的表达水平低于其他抗原（例如 HLA-C、HLA-DQ），但在基因座内以及不同细胞类型之间，有许多因素会影响静息和激活的 HLA 表达细胞。如果没有特定的启动子蛋白 NLRC5（对于 HLA I 类）和 CIITA（对于 II 类），HLA 通常不会表达。HLA 蛋白的产生量受启动子区域多态性、选择性外显子剪接位点、甲基化和 microRNA 定向降解等因素的影响。不同的位点受这些控制机制的多种组合的影响，使得 HLA 调节的预测变得困难，但测量每个 HLA 抗原的细胞表达的能力，结合循环 HLA 特异性抗体的知识，将导致更明智的算法来评估移植风险。甲基化和 microRNA 指导的降解。不同的位点受这些控制机制的多种组合的影响，使得 HLA 调节的预测变得困难，但测量每个 HLA 抗原的细胞表达的能力，结合循环 HLA 特异性抗体的知识，将导致更明智的算法来评估移植风险。甲基化和 microRNA 指导的降解。不同的位点受这些控制机制的多种组合的影响，使得 HLA 调节的预测变得困难，但测量每个 HLA 抗原的细胞表达的能力，结合循环 HLA 特异性抗体的知识，将导致更明智的算法来评估移植风险。