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Expansion of blood IgG4+ B, TH2, and regulatory T cells in patients with IgG4-related disease
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2017-08-19 , DOI: 10.1016/j.jaci.2017.07.024
Jorn J. Heeringa , A. Faiz Karim , Jan A.M. van Laar , Robert M. Verdijk , Dion Paridaens , P. Martin van Hagen , Menno C. van Zelm

Background

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition affecting various organs and has a diverse clinical presentation. Fibrosis and accumulation of IgG4+ plasma cells in tissue are hallmarks of the disease, and IgG4-RD is associated with increased IgG4 serum levels. However, disease pathogenesis is still unclear, and these cellular and molecular parameters are neither sensitive nor specific for the diagnosis of IgG4-RD.

Objective

Here we sought to develop a flow cytometric gating strategy to reliably identify blood IgG4+ B cells to study their cellular and molecular characteristics and investigate their contribution in disease pathogenesis.

Methods

Sixteen patients with histologically confirmed IgG4-RD, 11 patients with sarcoidosis, and 30 healthy subjects were included for 11-color flow cytometric analysis of peripheral blood for IgG4-expressing B cells and TH subsets. In addition, detailed analysis of activation markers and chemokine receptors was performed on IgG4-expressing B cells, and IgG4 transcripts were analyzed for somatic hypermutations.

Results

Cellular and molecular analyses revealed increased numbers of blood IgG4+ memory B cells in patients with IgG4-RD. These cells showed reduced expression of CD27 and CXCR5 and increased signs of antibody maturation. Furthermore, patients with IgG4-RD, but not patients with sarcoidosis, had increased numbers of circulating plasmablasts and CD21low B cells, as well as TH2 and regulatory T cells, indicating a common disease pathogenesis in patients with IgG4-RD.

Conclusion

These results provide new insights into the dysregulated IgG4 response in patients with IgG4-RD. A specific “peripheral lymphocyte signature” observed in patients with IgG4-RD, could support diagnosis and treatment monitoring.



中文翻译:

血液的IgG的扩张4 + B,T ħ 2,和调节性T细胞的患者有IgG 4 -相关疾病

背景

IgG 4相关疾病(IgG 4 -RD)是一种影响各种器官的全身性纤维炎性疾病,具有多种临床表现。IgG 4 +浆细胞的纤维化和在组织中的蓄积是该疾病的标志,而IgG 4 -RD与IgG 4血清水平升高相关。然而,疾病的发病机理仍然不清楚,并且这些细胞和分子参数对于IgG 4 -RD的诊断既不敏感也不特异性。

客观的

在这里,我们寻求开发一种流式细胞术门控策略,以可靠地鉴定血液IgG 4 + B细胞,以研究其细胞和分子特征,并研究其在疾病发病机理中的作用。

方法

包括16例经组织学证实为IgG 4 -RD的患者,11例结节病患者和30例健康受试者,以11色流式细胞术分析外周血中表达IgG 4的B细胞和T H亚型。此外,对表达IgG 4的B细胞进行了活化标记和趋化因子受体的详细分析,并分析了IgG 4转录本的体细胞超突变。

结果

细胞和分子分析显示,患有IgG 4 -RD的患者血液IgG 4 +记忆B细胞数量增加。这些细胞显示CD27和CXCR5的表达减少,抗体成熟的迹象增加。此外,IgG 4 -RD患者(而非结节病患者)的循环浆母细胞和CD21B细胞以及T H 2和调节性T细胞数量增加,表明IgG 4 -RD患者常见疾病发病机制。

结论

这些结果为IgG 4 -RD患者的IgG 4反应失调提供了新的见解。在IgG 4 -RD患者中观察到的特定“外周淋巴细胞标志”可以支持诊断和治疗监测。

更新日期:2017-08-19
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