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系统性红斑狼疮患者静止期外周 B 细胞异常:记忆 B 细胞和膜 CD19 表达减少。

Peripheral B cell abnormalities in patients with systemic lupus erythematosus in quiescent phase: decreased memory B cells and membrane CD19 expression.

机构信息

CNRS UPR9021, Université de Strasbourg (UDS), Hopitaux Universitaires de Strasbourg, Strasbourg, France.

出版信息

J Autoimmun. 2010 Jun;34(4):426-34. doi: 10.1016/j.jaut.2009.11.002. Epub 2009 Dec 5.

Abstract

B lymphocytes from patients with systemic lupus erythematosus (SLE) are hyperactive and produce autoantibodies. Several B cell phenotype characteristics such as the expansion of activated populations, and of a newly identified memory compartment have already been reported. These results are not easy to interpret because of the clinical heterogeneity of SLE, as well as the difficulties to establish homogeneous and well defined groups taking in consideration the activity of the disease and the various therapies. However, although many mediators and mechanisms can contribute to the clinical presentation and subsequent progression of individuals with SLE, several data suggest that some intrinsic B cells abnormalities may be central to the disease process. In this view, we have analysed the phenotype of B cells from 18 patients with quiescent diseases (mean SLEDAI score below 2) and from 11 healthy controls. B cell surface marker expression was determined by flow cytometry. We analysed the main B cell sub-populations. We demonstrate the persistence of plasmocyte-differentiated and -activated B cells even in quiescent patients. However, quiescent patients display a decrease in memory B cells that could reflect the control of their disease. Above all, we describe a lower membrane expression of the CD19 protein on all B cells in every patient compared to controls. This lower CD19 expression is associated with reduced CD45 levels. It is not associated with an evident gene expression alteration and in vitro stimulation restores a control phenotype. These findings suggest certain mechanisms of lupus development.

摘要

系统性红斑狼疮(SLE)患者的 B 细胞过度活跃,并产生自身抗体。已经报道了几种 B 细胞表型特征,例如激活群体的扩张,以及新鉴定的记忆区室。由于 SLE 的临床异质性以及考虑到疾病的活动和各种治疗方法,难以建立同质且明确的组,因此这些结果不易解释。然而,尽管许多介质和机制可能有助于 SLE 个体的临床表现和随后的进展,但有几项数据表明,某些内在的 B 细胞异常可能是疾病过程的核心。在这种情况下,我们分析了 18 名疾病稳定(SLEDAI 评分均低于 2)的患者和 11 名健康对照者的 B 细胞表型。通过流式细胞术测定 B 细胞表面标记物的表达。我们分析了主要的 B 细胞亚群。我们证明了即使在疾病稳定的患者中,浆细胞分化和激活的 B 细胞仍然存在。然而,疾病稳定的患者表现出记忆 B 细胞减少,这可能反映了他们疾病的控制。最重要的是,与对照组相比,我们描述了每个患者的所有 B 细胞上 CD19 蛋白的膜表达降低。这种较低的 CD19 表达与 CD45 水平降低相关。它与明显的基因表达改变无关,体外刺激可恢复对照表型。这些发现提示了狼疮发展的某些机制。

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