Hosokawa Kohei, Nakao Shinji
Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University.
Japanese Red Cross Ishikawa Blood Center.
Rinsho Ketsueki. 2022;63(8):899-905. doi: 10.11406/rinketsu.63.899.
Human leukocyte antigen (HLA) class I allele-lacking [HLA (-)] leukocytes provide compelling evidence that cytotoxic T-lymphocytes are involved in the development of aplastic anemia (AA). However, the clinical significance and precise mechanisms underlying clonal hematopoiesis by HLA (-) hematopoietic stem progenitor cells remain unknown. In HLA (-) cells from patients with AA, we discovered a common nonsense mutation at codon19 (c.19C>T, p.R7X) in exon1 (Exon1) of different HLA-A and HLA-B alleles. Exon1 mutation detection using droplet digital polymerase chain reaction (ddPCR) is a powerful tool for diagnosing immune pathophysiology in patients with bone marrow failure. We also looked at the prognosis of 633 patients with AA, including 127 with HLA (-) leukocytes who had been followed up for a long time. In Japanese patients with AA, HLA (-) leukocytes and concomitant aberrant clones were not associated with clonal evolution to MDS/AML. In patients with AA and both marker (-) leukocytes, HLA (-) leukocytes may indicate a lower risk of developing secondary paroxysmal nocturnal hemoglobinuria (PNH). Detecting HLA (-) leukocytes is critical for managing patients with AA and assisting physicians in selecting appropriate therapy.
缺乏人类白细胞抗原（HLA）I类等位基因的[HLA（-）]白细胞提供了令人信服的证据，表明细胞毒性T淋巴细胞参与了再生障碍性贫血（AA）的发生发展。然而，HLA（-）造血干祖细胞克隆性造血的临床意义和确切机制仍不清楚。在AA患者的HLA（-）细胞中，我们在不同HLA - A和HLA - B等位基因的外显子1（Exon1）第19密码子处发现了一个常见的无义突变（c.19C>T，p.R7X）。使用液滴数字聚合酶链反应（ddPCR）检测外显子1突变是诊断骨髓衰竭患者免疫病理生理学的有力工具。我们还观察了633例AA患者的预后，其中包括127例长期随访的HLA（-）白细胞患者。在日本AA患者中，HLA（-）白细胞和伴随的异常克隆与向骨髓增生异常综合征/急性髓系白血病（MDS/AML）的克隆进化无关。在AA且两种标记（-）白细胞的患者中，HLA（-）白细胞可能表明发生继发性阵发性睡眠性血红蛋白尿（PNH）的风险较低。检测HLA（-）白细胞对于管理AA患者和协助医生选择合适的治疗方法至关重要。
