Molecular characterization of circulating plasma cells in patients with active systemic lupus erythematosus.

Molecular characterization of circulating plasma cells in patients with active systemic lupus erythematosus.
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DOI:
10.1371/journal.pone.0044362
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Lipsky PE
Lipsky PE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lugar PL;Love C;Grammer AC;Dave SS;Lipsky PE

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系统性红斑狼疮(SLE)是一种全身性自身免疫性疾病,其特征是B细胞异常活化和循环浆细胞(PC)频率增加。SLE中循环PC和B细胞的分子特征和性质尚未完全确定。基因表达的微阵列分析用于表征活动性SLE受试者的循环PC。使用流式细胞术从活动性SLE血液、正常血液和正常扁桃体中分选PC和比较B细胞群。然后比较分选的B细胞群的基因表达谱。SLE PC表现出与扁桃体PC相似的基因表达特征。SLE PC与正常扁桃体PC和扁桃体浆母细胞(PB)之间基因表达的差异表明,在前者人群中存在成熟的IG分泌细胞表型。尽管如此,SLE PC的基因表达与以前发表的正常骨髓PC的基因表达谱的约一半不同,表明这些细胞尚未达到完全成熟的状态。包括CXCR4和S1P1在内的几种基因的异常表达提示了SLE PC在循环中持续存在的机制。所有的SLE B细胞群体都显示了以前仅在未分离的SLE外周血单核细胞中报道的干扰素(IFN)基因特征。这些数据表明SLE PC是一个独特的IG分泌细胞群体,其基因表达谱表明成熟但未完全分化的表型。
Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared. SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P1, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype.
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