Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus - Implications for the induction and maintenance of the autoimmune process
Expansion of toll-like receptor 9-expressing B cells in active systemic lupus erythematosus - Implications for the induction and maintenance of the autoimmune process
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DOI：
10.1002/art.22197
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发表时间：
2006-11-01
影响因子：
--
通讯作者：
Boumpas, Dimitrios T.
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文献类型：
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作者：
Papadimitraki, Eva D.;Choulaki, Christianna;Boumpas, Dimitrios T.
目标。Toll样受体是先天免疫中的一种模式相关受体，可能参与自身抗原的识别和致病自身抗体的产生。本研究检测系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)亚群中不同TLRs的表达及功能。用流式细胞仪检测了50例SLE活动期患者(SLE疾病活动性指数[SLEDAI]积分=8；n=26)、稳定期SLE患者(SLEDAI积分=8；n=24)和20例健康对照外周血单个核细胞TLRs的表达。TLR在PBMC不同亚群上的表达(TLR-2和TLR-4用膜染色；TLR-3和TLR-9用细胞内染色)。TLR功能是通过用特定的配体刺激PBMC来实现的。活动期SLE患者B细胞和单核细胞表达TLR-9的比例(均值+/-SD分别为49.5+/-24.4%和30.7+/-24.1%)明显高于非活动期患者(分别为22.8+/-19.6%和14.3+/-8.4%，P=0.02和P=0.03)。活动期SLE患者B细胞中，浆细胞和记忆性B细胞表达TLR-9的比例增加。表达TLR9的B细胞百分比的增加与抗双链抗体的存在有关(P=0.007)。活动性疾病患者的血清治疗增加了健康对照组血清中表达TLR-9的浆细胞的百分比。活动期疾病患者的B细胞经TLR-9刺激后可增强其对人类白细胞抗原-DR的诱导作用。活动期SLE患者外周血记忆B细胞和浆细胞表达TLR-9的比例增加。凋亡细胞死亡时释放的内源性核酸可能通过TLR-9刺激B细胞，参与SLE的发病。
Objective. Toll-like receptors (TLRs) are pattern-associated receptors in innate immunity that may be involved in the recognition of self antigens and the production of pathogenic autoantibodies. This study was undertaken to examine the expression and function of various TLRs in subpopulations of peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).Methods. The expression of TLRs in PBMCs from 50 SLE patients with active disease (SLE Disease Activity Index [SLEDAI] score >= 8; n = 26) or inactive disease (SLEDAI score < 8; n = 24) and 20 healthy controls was studied by flow cytometry. TLR expression was assessed on various subpopulations of PBMCs (TLR-2 and TLR-4 by membrane staining; TLR-3 and TLR-9 by intracellular staining). TLR function was accessed by stimulating PBMCs with specific ligands.Results. The proportion of B cells and monocytes expressing TLR-9 was higher among patients with active SLE (mean +/- SD 49.5 +/- 24.4% and 30.7 +/- 24.1%, respectively) than among patients with inactive disease (22.8 +/- 19.6% and 14.3 +/- 8.4%, respectively; P = 0.02 and P = 0.03). Among B cells, the proportion of plasma cells and memory B cells expressing TLR-9 was increased in patients with active SLE. Increased percentages of TLR-9-expressing B cells correlated with the presence of anti-double-stranded DNA antibodies (P = 0.007). Treatment with serum from patients with active disease increased the percentage of TLR-9-expressing plasma cells in serum from healthy controls. Enhanced induction of HLA-DR after TLR-9 stimulation was documented in B, cells from patients with active disease.Conclusion. In patients with active SLE, the proportion of peripheral blood memory B cells and plasma cells expressing TLR-9 is increased. Endogenous nucleic acids released during apoptotic cell death may stimulate B cells via TLR-9 and contribute to SLE pathogenesis.