BACKGROUND Neuropsychiatric manifestations are frequent in patients with systemic lupus erythematosus (SLE), yet the etiology and pathogenesis of brain damage in SLE remains unclear. Because the production of autoantibodies, formation and deposition of immunocomplexes are major serological characteristics of SLE, the elevated level of serum immunoglobulin may contribute to brain tissue injury of SLE. To testify this, in this study, we examined whether immunoglobulin G (IgG) in the serum of SLE patients affects the cellular functions in central nervous system and the potential mechanism. METHODS In vivo intracerebral injection of SLE-serum in mouse was used to activate microglia and the production of pro-inflammatory cytokine was assessed by ELISA. Sera was divided into IgG and IgG depleted fractions, while IgG was further divided into Fc and Fab fragments to examine which part has an effect on microglia. Flow cytometry, immunofluorescence and quantitative PCR (qPCR) were used to verify the synergistic effect of B-cell activating factor (BAFF) on IgG stimulation of microglia. RESULTS We found that IgG in lupus sera can induce M1 activation of brain microglia following intraventricular injection into normal mice, and BAFF facilitates this process. In vitro, we identified that IgG bound to microglia through Fc rather than Fab fragments, and BAFF up-regulated the expression of Fc receptors (FcγR) on the surface of microglia, consequently, promote IgG binding to microglia. CONCLUSION Our results suggest that lupus serum IgG causes inflammatory responses of microglia by involving the Fc signaling pathway and the activity could be up-regulated by BAFF. Accordingly, disruption of the FcγR-mediated signaling pathway and blockade of microglia activation may be a therapeutic target in patients with neuropsychiatric lupus erythematosus.

中文翻译：

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狼疮血清 IgG 通过 Fc 片段依赖性方式诱导小胶质细胞激活，并受 B 细胞激活因子调节。


背景神经精神症状在系统性红斑狼疮（SLE）患者中很常见，但SLE脑损伤的病因和发病机制仍不清楚。由于自身抗体的产生、免疫复合物的形成和沉积是SLE的主要血清学特征，因此血清免疫球蛋白水平升高可能与SLE的脑组织损伤有关。为了证明这一点，在本研究中，我们检测了SLE患者血清中的免疫球蛋白G（IgG）是否影响中枢神经系统的细胞功能及其潜在机制。方法在小鼠体内脑内注射SLE血清来激活小胶质细胞，并通过ELISA评估促炎细胞因子的产生。将血清分为 IgG 和 IgG 去除部分，而 IgG 进一步分为 Fc 和 Fab 片段，以检查哪一部分对小胶质细胞有影响。采用流式细胞术、免疫荧光和定量PCR（qPCR）验证B细胞激活因子（BAFF）对小胶质细胞IgG刺激的协同作用。结果我们发现狼疮血清中的 IgG 在正常小鼠脑室内注射后可诱导脑小胶质细胞 M1 激活，而 BAFF 促进了这一过程。在体外，我们发现IgG通过Fc而不是Fab片段与小胶质细胞结合，并且BAFF上调小胶质细胞表面Fc受体（FcγR）的表达，从而促进IgG与小胶质细胞结合。结论我们的结果表明狼疮血清IgG通过参与Fc信号通路引起小胶质细胞的炎症反应，并且BAFF可以上调该活性。 因此，破坏 FcγR 介导的信号通路和阻断小胶质细胞活化可能是神经精神性红斑狼疮患者的治疗目标。