Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease.
Circulating plasmablasts/plasma cells: a potential biomarker for IgG4-related disease.
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循环浆母细胞/浆细胞：IgG4 相关疾病的潜在生物标志物。
DOI：
10.1186/s13075-017-1231-2
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发表时间：
2017-02-10
影响因子：
4.9
通讯作者：
Lipsky PE
中科院分区：
文献类型：
--
作者：
Lin W;Zhang P;Chen H;Chen Y;Yang H;Zheng W;Zhang X;Zhang F;Zhang W;Lipsky PE
免疫球蛋白G4（IgG 4）相关疾病（IgG 4-RD）是一种多系统纤维炎症性疾病。我们以前报道过，表达CD 19 + CD 24 − CD 38 hi的循环细胞群在IgG 4-RD患者中增加。在这项研究中，我们的目的是记录该细胞群代表循环浆母细胞/浆细胞，以确定这些分泌IgG 4的浆母细胞/浆细胞的详细表型和基因表达谱，并确定该B细胞谱系亚群是否可以成为IgG 4相关疾病（IgG 4-RD）的生物标志物。共评价了42例未经治疗的IgG 4-RD患者。通过流式细胞术评估并分选外周B细胞亚群，包括CD 19 + CD 24-CD 38 hi浆母细胞/浆细胞、CD 19 + CD 24 + CD 38-记忆B细胞、CD 19 + CD 24 intCD 38 int幼稚B细胞和CD 19 + CD 24 hiCD 38 hi调节性B细胞。微阵列分析用于测量循环B细胞谱系亚群的基因表达。通过流式细胞仪分析评估其他表面标志物（包括CD 27、CD 95和人类白细胞抗原（HLA）-DR），对CD 19 + CD 24-CD 38 hi浆母细胞/浆细胞进行进一步表征。此外，在体外培养各种B细胞谱系亚群，并通过流式细胞仪珠阵列测量IgG 4浓度。在未经治疗的IgG 4-RD患者中，外周CD 19 + CD 24 − CD 38 hi浆母细胞/浆细胞亚群增加，并与血清IgG 4水平、受累器官数量和IgG 4相关疾病应答者指数呈正相关。糖皮质激素治疗后下降。通过基因表达谱对浆母细胞/浆细胞群体的表征记录了典型的浆母细胞/浆细胞特征，其具有较高的X盒结合蛋白1和IFN调节因子4的表达，但较低的配对盒基因5和B细胞淋巴瘤6蛋白的表达。此外，CD 27、CD 95和HLA-DR在IgG 4-RD患者的CD 19 + CD 24 − CD 38 hi浆母细胞/浆细胞上高度表达。此外，CD 19 + CD 24 − CD 38 hi浆母细胞/浆细胞比其他B细胞群体分泌更多的IgG 4。循环中的CD 19 + CD 24 − CD 38 hi浆母细胞/浆细胞在活性IgG 4-RD中升高，在糖皮质激素治疗后降低。这种分泌IgG 4的浆母细胞/浆细胞群体可能是诊断和评估治疗反应的潜在有用生物标志物。
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a multisystem fibroinflammatory disease. We previously reported that a circulating cell population expressing CD19+CD24−CD38hi was increased in patients with IgG4-RD. In this study, we aimed to document that this cell population represented circulating plasmablasts/plasma cells, to identify the detailed phenotype and gene expression profile of these IgG4-secreting plasmablasts/plasma cells, and to determine whether this B-cell lineage subset could be a biomarker in IgG4-related disease (IgG4-RD). A total of 42 untreated patients with IgG4-RD were evaluated. Peripheral B-cell subsets, including CD19+CD24−CD38hi plasmablasts/plasma cells, CD19+CD24+CD38− memory B cells, CD19+CD24intCD38int naïve B cells, and CD19+CD24hiCD38hi regulatory B cells, were assessed and sorted by flow cytometry. Microarray analysis was used to measure gene expression of circulating B-cell lineage subsets. Further characterization of CD19+CD24−CD38hi plasmablasts/plasma cells was carried out by evaluating additional surface markers, including CD27, CD95, and human leukocyte antigen (HLA)-DR, by flow cytometric assay. In addition, various B-cell lineage subsets were cultured in vitro and IgG4 concentrations were measured by cytometric bead array. In untreated patients with IgG4-RD, the peripheral CD19+CD24−CD38hi plasmablast/plasma cell subset was increased and positively correlated with serum IgG4 levels, the number of involved organs, and the IgG4-related Disease Responder Index. It decreased after treatment with glucocorticoids. Characterization of the plasmablast/plasma cell population by gene expression profiling documented a typical plasmablast/plasma cell signature with higher expression of X-box binding protein 1 and IFN regulatory factor 4, but lower expression of paired box gene 5 and B-cell lymphoma 6 protein. In addition, CD27, CD95, and HLA-DR were highly expressed on CD19+CD24−CD38hi plasmablasts/plasma cells from patients with IgG4-RD. Furthermore, CD19+CD24−CD38hi plasmablasts/plasma cells secreted more IgG4 than other B-cell populations. Circulating CD19+CD24−CD38hi plasmablasts/plasma cells are elevated in active IgG4-RD and decreased after glucocorticoid treatment. This IgG4-secreting plasmablast/plasma cell population might be a potentially useful biomarker for diagnosis and assessing response to treatment.