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IL-21 dependent Granzyme B production of B-cells is decreased in patients with lupus nephritis
Clinical Immunology ( IF 8.6 ) Pub Date : 2017-12-21 , DOI: 10.1016/j.clim.2017.12.005
Mariam Rabani , Benjamin Wilde , Katharina Hübbers , Shilei Xu , Andreas Kribben , Oliver Witzke , Sebastian Dolff

Objectives

B-cells play a crucial role in the pathogenesis of lupus nephritis. Recently, a separate subset has been discovered characterized by expression of Granzyme B. The aim of this study is to investigate this subset in patients with systemic lupus erythematosus (SLE).

Methods

Isolated PBMCs of SLE-patients (n = 30) and healthy controls (n = 21) were in vitro stimulated with CPG, IgG + IgM and IL-21. Patients were sub-grouped in patients with and without biopsy proven lupus nephritis. B-cells were analyzed for intracellular Granzyme B expression by flow cytometry.

Results

The strongest stimulus for Granzyme B secretion of B-cells was IgG + IgM in presence of IL-21. SLE-patients had a significant decreased percentage of Granzyme B+ B-cells in particular SLE-patients with active disease and with lupus nephritis.

Conclusions

The frequency of GrB + producing B-cells is reduced in SLE patients. This may contribute to an imbalanced B-cell regulation towards effector B-cells which might promote the development of lupus nephritis.



中文翻译:

狼疮性肾炎患者IL-21依赖性B细胞粒酶B的产生减少

目标

B细胞在狼疮性肾炎的发病机理中起着至关重要的作用。最近,发现了一个单独的亚群,其特征是粒酶B的表达。这项研究的目的是研究系统性红斑狼疮(SLE)患者的这一亚群。

方法

用CPG,IgG + IgM和IL-21体外刺激SLE患者(n = 30)和健康对照组(n = 21)的分离的PBMC。患者分为有活检和无活检证实的狼疮性肾炎患者。通过流式细胞术分析B细胞的细胞内颗粒酶B表达。

结果

在IL-21存在下,B细胞颗粒酶B分泌的最强刺激是IgG + IgM。SLE患者尤其是患有活动性疾病和狼疮性肾炎的SLE患者的颗粒酶B + B细胞百分比显着下降。

结论

SLE患者中产生GrB +的B细胞的频率降低。这可能导致B细胞对效应B细胞的调节不平衡,这可能会促进狼疮性肾炎的发展。

更新日期:2017-12-21
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