Elevated numbers of immature/transitional CD2I- B lymphocytes and deficiency of memory CD27+ B cells identify patients with active chronic graft-versus-host disease

Elevated numbers of immature/transitional CD2I- B lymphocytes and deficiency of memory CD27+ B cells identify patients with active chronic graft-versus-host disease
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DOI:
10.1016/j.bbmt.2007.10.009
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发表时间:
2008-02-01
影响因子:
4.3
通讯作者:
Pickl, Winfried F.
Pickl, Winfried F.
中科院分区:
医学2区
文献类型:
--
作者:
Greinix, Hildegard T.;Pohlreich, David;Pickl, Winfried F.

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慢性移植物抗宿主病(cGVHD)是异基因造血干细胞移植(HSCT)的主要并发症,也是非复发死亡率(NRM)的主要原因。目前,缺乏用于诊断和监测cGVHD活性的基于生物学的标志物。70例接受HSCT的患者入组了一项初步研究,其中21例无cGVHD,49例有活动性或消退的cGVHD。评价包括临床参数,包括cGVHD严重程度和感染。采用多参数流式细胞术分析外周血细胞。通过表面IgD、CD 21和CD 27染色进一步细分CD 19(+)B细胞区室。在有和没有cGVHD的组之间没有观察到绝对B、T和自然杀伤(NK)细胞数量的显著差异。然而,未成熟/过渡性CD 19(+)/CD 21(-)B细胞数量的升高(B淋巴细胞> 15%)与严重感染的发生相关(P = 0.003)。最重要的是,所有患有活动性cGVHD和CD 19 +/CD 21- B淋巴细胞数量升高的患者都经历了严重感染(P = .00016)。与从未经历过cGVHD的患者相比,活动性cGVHD患者的非类别转换和类别转换记忆B细胞的数量显著降低(P = 0.002和P = 0.001)。循环B淋巴细胞区室的扰动可以作为监测cGVHD活性及其对免疫系统影响的新生物标志物。一项对HSCT后连续评估B细胞重建的AML患者的前瞻性研究是必要的。(c)2008年美国血液和骨髓移植协会。
Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of non-relapse mortality (NRM). Currently, biology-based markers are lacking both for diagnosis and for monitoring the activity of cGVHD. Seventy patients who received HSCT were enrolled in a pilot study, including 21 without cGVHD and 49 with active or resolved cGVHD. Evaluations were comprised of clinical parameters including cGVHD severity and infections. Peripheral blood cells were analyzed by multi-parameter flow cytometry. The CD19(+) B cell compartment was further subdivided by staining for surface IgD, CD21 and CD27. No significant differences in absolute B, T, and natural killer (NK) cell numbers were observed between the groups with and without cGVHD. However, elevated numbers (> 15% of B lymphocytes) of immature/transitional CD19(+)/CD21(-) B cells were associated with the occurrence of severe infections (P = .003). Most significantly, all patients with active cGVHD and elevated numbers of CD19+/CD21- B lymphocytes experienced severe infections (P = .00016). The numbers of both non-class-switched and class-switched memory B cells were significantly lower in patients with active cGVHD when compared to patients who never experienced cGVHD (P = .002 and P = .001). Perturbation of circulating B lymphocyte compartments may serve as a novel biomarker for monitoring cGVHD activity and its impact on the immune system. A prospective study on unselected patients assessed serially for B cell reconstitution after HSCT is warranted. (c) 2008 American Society for Blood and Marrow Transplantation.