Japanese Red Cross Ishikawa Blood Center, 4-445 Fujiekita, Kanazawa, Ishikawa, 920-0345, Japan.
Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.
Int J Hematol. 2024 Mar;119(3):231-239. doi: 10.1007/s12185-022-03519-1. Epub 2023 Jan 7.
Differential diagnosis of pancytopenia with bone marrow (BM) hypoplasia represented by aplastic anemia (AA) is often challenging for physicians, because no laboratory tests have been established, until recently, to distinguish immune-mediated BM failure, which includes acquired AA (aAA) and a subset of low-risk myelodysplastic syndrome (MDS), from non-immune BM failure, which is primarily caused by genetic abnormalities in hematopoietic stem cells (HSCs). HSCs of healthy individuals often undergo somatic mutations, and some acquire phenotypic changes that allow them to escape immune attack against themselves. Once an immune attack against HSCs occurs, HSCs that undergo somatic mutations survive the immune attack and continue to produce their progenies with the same genetic or phenotypic changes. The presence of mature blood cells derived from mutated HSCs in the peripheral blood serves as evidence of the immune-mediated destruction of HSCs. Glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) blood cells and HLA class I allele-lacking (HLA[-]) leukocytes are two major aberrant cell types that represent the immune mechanism underlying BM failure. This review focuses on the importance of identifying immune mechanisms using laboratory markers, including GPI(-) cells and HLA(-) leukocytes, in the management of BM failure.
骨髓（BM）再生不良表现为再生障碍性贫血（AA）的全血细胞减少症的鉴别诊断一直是医生面临的挑战，因为直到最近，还没有实验室检查可以区分免疫介导的 BM 衰竭，包括获得性 AA（aAA）和低风险骨髓增生异常综合征（MDS）的一部分，与非免疫 BM 衰竭，主要是由造血干细胞（HSCs）中的遗传异常引起的。健康个体的 HSCs 经常发生体细胞突变，并且一些获得表型变化，使它们能够逃避针对自身的免疫攻击。一旦对 HSCs 发生免疫攻击，经历体细胞突变的 HSCs 就会在免疫攻击中存活下来，并继续产生具有相同遗传或表型变化的后代。外周血中源自突变 HSCs 的成熟血细胞的存在证明了对 HSCs 的免疫介导破坏。糖基磷脂酰肌醇锚定蛋白缺乏（GPI[-]）血细胞和 HLA Ⅰ类等位基因缺失（HLA[-]）白细胞是两种主要的异常细胞类型，代表了 BM 衰竭的免疫机制。这篇综述重点介绍了使用实验室标志物（包括 GPI[-]细胞和 HLA[-]白细胞）识别免疫机制在 BM 衰竭管理中的重要性。
