Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Blood. 2018 Jan 4;131(1):144-152. doi: 10.1182/blood-2017-07-799270. Epub 2017 Nov 1.
Patients refractory to platelet transfusions because of alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then, patients with broad immunization or rare haplotypes may not have suitable donors. In these patients, transfusions with platelets showing low HLA class I expression may be an alternative to fully HLA-matched transfusions. In this study, we quantified the proportion of donors with consistently low HLA-B8, -B12, and -B35 expression on platelets using human monoclonal antibodies specific for these antigens. Furthermore, as model for in vivo clearance, antibody-mediated internalization of these platelets by macrophages was investigated. The expression of HLA-B8, -B12, or -B35 on platelets was extremely variable between individuals (coefficients of variation, 41.4% to 73.6%). For HLA-B8, but not for HLA-B12 or -B35, this variation was in part explained by zygosity. The variation was most pronounced in, but not exclusive to, platelets. Expression within one donor was consistent over time. Remarkably, 32% of 113 HLA-B8, 34% of 98 HLA-B12, and 9% of 66 HLA-B35 donors showed platelet antigen expression that was not or only minimally above background. Antibody-mediated internalization of platelets by macrophages correlated with antibody opsonization and antigen expression and was absent in platelets with low or minimal HLA expression. In conclusion, our findings indicate that a substantial proportion of donors have platelets with consistently low expression of specific HLA class I antigens. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches.
由于同种免疫而对血小板输注无效的患者需要 HLA 匹配的血小板，只有在有大量 HLA 分型供体库的情况下才有可能。然而，即使在这种情况下，具有广泛免疫或罕见单倍型的患者可能也没有合适的供体。在这些患者中，输注 HLA Ⅰ类抗原低表达的血小板可能是替代完全 HLA 匹配输注的一种选择。在这项研究中，我们使用针对这些抗原的人源单克隆抗体来定量分析血小板上 HLA-B8、-B12 和 -B35 表达一致较低的供体比例。此外，作为体内清除的模型，研究了巨噬细胞通过抗体介导内化这些血小板的情况。个体之间血小板上 HLA-B8、-B12 或 -B35 的表达差异非常大（变异系数为 41.4%至 73.6%）。对于 HLA-B8，但不是 HLA-B12 或 -B35，这种变异性部分与基因型有关。这种变异性在血小板中最为明显，但并非仅限于血小板。同一供体的表达在时间上是一致的。值得注意的是，在 113 名 HLA-B8 供体中，有 32%，在 98 名 HLA-B12 供体中，有 34%，在 66 名 HLA-B35 供体中，表现出的血小板抗原表达低于或仅略高于背景。巨噬细胞通过抗体介导内化血小板与抗体调理作用相关，并且在 HLA 表达低或最低的血小板中不存在。总之，我们的发现表明，相当一部分供体的血小板具有特定 HLA Ⅰ类抗原的一致低表达。这些血小板可能用于治疗针对这些特定抗原的抗体产生的难治性患者，尽管存在 HLA 不匹配的情况。
