Hematopoietic stem progenitor cells lacking HLA differ from those lacking GPI-anchored proteins in the hierarchical stage and sensitivity to immune attack in patients with acquired aplastic anemia
Hematopoietic stem progenitor cells lacking HLA differ from those lacking GPI-anchored proteins in the hierarchical stage and sensitivity to immune attack in patients with acquired aplastic anemia
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获得性再生障碍性贫血患者中，缺乏 HLA 的造血干祖细胞与缺乏 GPI 锚定蛋白的造血干祖细胞在层次阶段和对免疫攻击的敏感性方面有所不同
DOI：
10.1038/s41375-021-01202-8
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发表时间：
2021
期刊：
影响因子：
11.4
通讯作者：
Nakao S
中科院分区：
文献类型：
--
作者：
Yoroidaka T;Hosokawa K;Imi T;Mizumaki H;Katagiri T;Ishiyama K;Yamazaki H;Azuma F;Nanya Y;Ogawa S;Nakao S
为了研究获得性再生障碍性贫血(AA)患者糖基化磷脂酰肌醇锚定蛋白缺失(GPI[−])和人类白细胞抗原I类等位基因缺失(HLAI[−])造血干细胞(HSPC)的特征，我们对56例AA缓解期患者的外周血(PB)进行了研究，这些患者既有 (A组)，又有GPI(−)(n= 34，B组)和HLAI(−)(n= 9，C组)。A组77%(10/13)的患者外周血包括血小板在内的外周血中均有−细胞，而仅23%(3/13)的患者外周血中有−细胞，其中位数为−(21.2%)，显著高于−(0.28%，P<； )。B组和C组比较，−细胞的谱系多样性高于−细胞。对A组7例患者的纵向研究显示，在环孢素(CsA)治疗有效的4例患者中，人类白细胞抗原(−)粒细胞百分比逐渐下降，4例环孢素A(CsA)缓解组患者的GpI(−)粒细胞比例依次升高，在3例CsA持续缓解期患者中，人类白细胞抗原(−)粒细胞数增加，GpI(−)粒细胞数稳定或下降。这些发现表明，在AA患者中，人类白细胞抗原(−)型HSPC与GPI(−)型HSPC在层级阶段和对免疫攻击的敏感性上有所不同。
To characterize glycosylphosphatidylinositol-anchored protein-deficient (GPI[−]) and HLA-class I allele-lacking (HLA[−]) hematopoietic stem progenitor cells (HSPCs) in acquired aplastic anemia (AA), we studied the peripheral blood (PB) of 56 AA patients in remission who possessed both (n= 13, Group A) or either GPI(−) (n= 34, Group B) and HLA(−) (n= 9, Group C) cell populations. Seventy-seven percent (10/13) of Group A had HLA(−) cells in all lineages of PB cells, including platelets, while only 23% (3/13) had GPI(−) cells in all lineages, and the median percentage of HLA(−) granulocytes in the total granulocytes (21.2%) was significantly higher than that of GPI(−) granulocytes (0.28%,P< 0.05). The greater lineage diversity in HLA(−) cells than in GPI(−) cells was also seen when Group B and Group C were compared. Longitudinal studies of seven patients in Group A showed a gradual decrease in the percentage of HLA(−) granulocytes, with a reciprocal increase in the GPI(−) granulocytes in four patients responding to cyclosporine (CsA) and an increase in the HLA(−) granulocytes with a stable or declining GPI(−) granulocytes in three patients in sustained remission off CsA therapy. These findings suggest that HLA(−) HSPCs differ from GPI(−) HSPCs in the hierarchical stage and sensitivity to immune attack in AA.