Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia
Clinical significance and origin of leukocytes that lack HLA-A allele expression in patients with acquired aplastic anemia
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DOI：
10.1016/j.exphem.2016.05.013
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发表时间：
2016-10-01
影响因子：
2.6
通讯作者：
Nakao, Shinji
中科院分区：
文献类型：
--
作者：
Maruyama, Hiroyuki;Katagiri, Takamasa;Nakao, Shinji
为了深入了解获得性再生障碍性贫血（AA）患者6号染色体短臂杂合性拷贝数中性缺失导致白细胞缺乏人白细胞抗原A （HLA-A）等位基因表达的来源和临床意义，我们采用高灵敏度流式细胞术检测144例AA患者HLA-A等位基因缺乏白细胞（hla - ls）的存在。71例新诊断患者中有18例（25.4%）检测到hla - ll， 73例既往治疗患者中有25例（34.2%）检测到hla - ll，占每个白细胞群的0.2-99.8%。43例HLA-LL+患者HLA-LL的谱系组合模式为粒细胞（Gs）、单核细胞（Ms）、B细胞（Bs）和T细胞（Ts； GMBT） 13例，GMB 16例，GM 11例，B单独存在3例。8例新诊断HLA-LL+患者抗胸腺细胞球蛋白联合环孢素治疗的有效率（100%）和2年无失败生存率（100%）显著高于23例HLA-LL-患者（两者均为52.2%）。这些数据表明，hla - ll是AA中存在免疫病理生理的有用标记，t细胞攻击造血祖细胞而不是造血干细胞可引发AA患者的骨髓衰竭。版权所有2016 ISEH -国际实验血液学学会Elsevier Inc.出版。
To gain insight into the origin and clinical significance of leukocytes that lack human leukocyte antigen A (HLA-A) allele expression caused by a copy-number-neutral loss of heterozygosity in the short arm of chromosome 6 in patients with acquired aplastic anemia (AA), we used a high-sensitivity flow cytometry assay to investigate the presence of HLA-A allele-lacking leukocytes (HLA-LLs) in 144 AA patients. HLA-LLs, accounting for 0.2-99.8% of each leukocyte population, were detected in 18 of 71 (25.4%) newly diagnosed patients and in 25 of 73 (34.2%) previously treated patients. The lineage combination patterns of the HLA-LLs in the 43 HLA-LL+ patients were granulocytes (Gs), monocytes (Ms), B cells (Bs), and T cells (Ts; GMBT) in 13 cases, GMB in 16 cases, GM in 11 cases, and B alone in three cases. The response rate to antithymocyte globulin plus cyclosporine therapy (100%) and the 2-year, failure-free survival rate (100%) in 8 newly diagnosed HLA-LL+ patients were significantly higher than in 23 HLA-LL- patients (52.2% for both). These data suggest that HLA-LLs are a useful marker of the presence of immune pathophysiology in AA and that T-cell attacks against hematopoietic progenitor cells, rather than against hematopoietic stem cells, can trigger bone marrow failure in AA patients. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.