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肿瘤坏死因子家族B细胞活化因子(BAFF)在活动期系统性红斑狼疮T细胞中的表达:BAFF在T细胞依赖性B细胞致病性自身抗体产生中的作用。

Expression of B-cell activating factor of the tumour necrosis factor family (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T cell-dependent B cell pathogenic autoantibody production.

作者信息

Morimoto S, Nakano S, Watanabe T, Tamayama Y, Mitsuo A, Nakiri Y, Suzuki J, Nozawa K, Amano H, Tokano Y, Kobata T, Takasaki Y

机构信息

Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.

出版信息

Rheumatology (Oxford). 2007 Jul;46(7):1083-6. doi: 10.1093/rheumatology/kem097. Epub 2007 May 11.

Abstract

OBJECTIVES

To determine whether B cell activating factor of the tumour necrosis factor family (BAFF) is involved in T cell-dependent B cell pathogenic autoantibody production in systemic lupus erythematosus (SLE).

METHODS

Peripheral blood mononuclear cells (PBMCs) from 23 SLE patients were analysed by flow cytometry to examine the intracellular expression of BAFF in CD4+ and CD8+ T cells and the surface expression of BAFF-receptor (R) and TACI on CD20+ B cells. Moreover, peripheral blood was used to determine the level of BAFF messenger RNA (mRNA) in CD4+ and CD8+ T cells and the level of BAFF-R mRNA in CD20+ B cells. Blocking of BAFF function with TACI-Ig measured anti-double-stranded DNA (dsDNA) antibodies by enzyme-linked immunosorbent assay (ELISA).

RESULTS

CD4+ and CD8+ T cells from patients with active SLE expressed intracellular BAFF whereas those from normal subjects did not. BAFF-R and TACI were expressed on B cells from both normal controls and patients with active SLE and there was no significant difference. CD4+ and CD8+ T cells from SLE patients expressed BAFF mRNA whereas those from normal controls did not. Expression of BAFF-R mRNA in CD20+ B cells showed no significant difference between SLE patients and normal controls. TACI-Ig suppressed spontaneous in vitro T cell-dependent B cell anti-dsDNA antibodies production on active SLE with kidney involvement.

CONCLUSIONS

BAFF may play a pathogenic role in SLE by stimulating T cell-dependent B cell autoantibodies production. Blockade of BAFF is a promising therapeutic approach for SLE especially in patients with kidney involvement.

摘要

目的

确定肿瘤坏死因子家族的B细胞活化因子(BAFF)是否参与系统性红斑狼疮(SLE)中T细胞依赖性B细胞致病性自身抗体的产生。

方法

采用流式细胞术分析23例SLE患者外周血单个核细胞(PBMC),检测CD4⁺和CD8⁺T细胞内BAFF的表达以及CD20⁺B细胞表面BAFF受体(R)和跨膜激活剂和钙调亲环素配体相互作用分子(TACI)的表达。此外,采用外周血检测CD4⁺和CD8⁺T细胞中BAFF信使核糖核酸(mRNA)水平以及CD20⁺B细胞中BAFF-R mRNA水平。用TACI-Ig阻断BAFF功能,通过酶联免疫吸附测定(ELISA)检测抗双链DNA(dsDNA)抗体。

结果

活动期SLE患者的CD4⁺和CD8⁺T细胞表达细胞内BAFF,而正常受试者的CD4⁺和CD8⁺T细胞不表达。正常对照和活动期SLE患者的B细胞均表达BAFF-R和TACI,且无显著差异。SLE患者的CD4⁺和CD8⁺T细胞表达BAFF mRNA,而正常对照的CD4⁺和CD8⁺T细胞不表达。CD20⁺B细胞中BAFF-R mRNA的表达在SLE患者和正常对照之间无显著差异。TACI-Ig抑制有肾脏受累的活动期SLE患者体外T细胞依赖性B细胞抗dsDNA抗体的自发产生。

结论

BAFF可能通过刺激T细胞依赖性B细胞自身抗体的产生在SLE中发挥致病作用。阻断BAFF是一种有前景的SLE治疗方法,尤其是对有肾脏受累的患者。

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