Immune dysregulation and dyserythropoiesis in the myelodysplastic syndromes
Immune dysregulation and dyserythropoiesis in the myelodysplastic syndromes
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DOI：
10.1111/j.1365-2141.2009.07921.x
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发表时间：
2010-01-01
影响因子：
6.5
通讯作者：
Terrazzano, Giuseppe
中科院分区：
文献类型：
--
作者：
Alfinito, Fiorella;Sica, Michela;Terrazzano, Giuseppe
骨髓增生异常综合征（MDS）是克隆性疾病，其特征是造血无效且具有白血病进展的高风险。免疫失调与发育异常克隆的出现、优势及进展的相关性已被提出，但缺乏深入了解这些关联的有价值的标准。本研究表明，与低危MDS患者的外周血（PB）相比，其骨髓（BM）中CD8淋巴细胞和成熟B细胞显著增加。调节性T细胞（Treg）在骨髓中的不同水平在这些患者中确定了两个亚组；只有Treg百分比较低的亚组显示出CD8淋巴细胞在骨髓中的募集。骨髓CD8细胞上CD54的不同水平揭示了中危-1（Int - 1）患者的两个亚组。骨髓CD8上CD54表达较高的亚组在CD4细胞上也显示出该分子的高水平。低危组中CD8淋巴细胞在骨髓中的募集和/或中危-1患者骨髓CD8上高CD54表达与更明显的红细胞生成异常和促红细胞生成素治疗相关。我们的数据阐明了免疫介导机制在低危和中危-1的MDS患者中的参与情况，并表明骨髓与外周血中免疫效应细胞的水平可作为对MDS患者进行更均匀分组的有用标准。
P>The myelodysplastic syndromes (MDS) are clonal disorders characterised by ineffective haematopoiesis with high risk of leukaemia progression. The relevance of immune-dysregulation for emergence, dominance and progression of dysplastic clones has been suggested, but valuable criteria to obtain insight into these connections are lacking. This study showed significant increase of CD8 lymphocytes and mature B cells in the bone marrow (BM) compared to peripheral blood (PB) of low risk MDS patients. Different BM levels of Regulatory T cells (Treg) identified two sub-groups in these patients; only the sub-group with lower Treg percentage showed BM recruitment of CD8 lymphocytes. Different levels of CD54 on BM CD8 cells revealed two sub-groups of Intermediate-1 (Int-1) patients. The sub-group with higher CD54 expression on BM CD8 showed high levels of this molecule also on CD4 cells. BM recruitment of CD8 lymphocytes in the low risk group and/or the presence of high CD54 expression on BM CD8 in Int-1 patients were associated with more pronounced dyserythropoiesis and erythropoietin treatment. Our data shed light on the involvement of immune-mediated mechanisms in Low and Int-1 risk MDS patients and suggest that BM versus PB levels of immune effectors could represent useful criteria for a more homogeneous grouping of MDS patients.