Papadimitraki Eva D, Choulaki Christianna, Koutala Eleni, Bertsias George, Tsatsanis Christos, Gergianaki Irini, Raptopoulou Amalia, Kritikos Heraklis D, Mamalaki Clio, Sidiropoulos Prodromos, Boumpas Dimitrios T
University of Crete Medical School, Heraklion, Greece.
Arthritis Rheum. 2006 Nov;54(11):3601-11. doi: 10.1002/art.22197.
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).
The expression of TLRs in PBMCs from 50 SLE patients with active disease (SLE Disease Activity Index [SLEDAI] score >or=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.
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.
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.
Toll样受体（TLRs）是天然免疫中与模式相关的受体，可能参与自身抗原的识别及致病性自身抗体的产生。本研究旨在检测系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMCs）亚群中各种TLRs的表达及功能。
采用流式细胞术研究50例活动期疾病（SLE疾病活动指数[SLEDAI]评分≥8；n = 26）或非活动期疾病（SLEDAI评分＜8；n = 24）的SLE患者以及20名健康对照者PBMCs中TLRs的表达。在PBMCs的不同亚群上评估TLR表达（通过膜染色检测TLR-2和TLR-4；通过细胞内染色检测TLR-3和TLR-9）。通过用特异性配体刺激PBMCs来评估TLR功能。
活动期SLE患者中表达TLR-9的B细胞和单核细胞比例高于非活动期疾病患者（分别为平均±标准差49.5±24.4%和30.7±24.1%）（分别为22.8±19.6%和14.3±8.4%；P = 0.02和P = 0.03）。在B细胞中，活动期SLE患者中表达TLR-9的浆细胞和记忆B细胞比例增加。表达TLR-9的B细胞百分比增加与抗双链DNA抗体的存在相关（P = 0.007）。用活动期疾病患者的血清处理可增加健康对照者血清中表达TLR-9的浆细胞百分比。在活动期疾病患者的B细胞中，记录到TLR-9刺激后HLA-DR的诱导增强。
在活动期SLE患者中，表达TLR-9的外周血记忆B细胞和浆细胞比例增加。凋亡细胞死亡过程中释放的内源性核酸可能通过TLR-9刺激B细胞并促进SLE发病机制。
