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狼疮性肾炎中的肾内细胞因子基因表达

Intrarenal cytokine gene expression in lupus nephritis.

作者信息

Chan Rebecca Wing-Yan, Lai Fernand Mac-Moune, Li Edmund Kwok-Ming, Tam Lai-Shan, Chow Kai-Ming, Lai Ka-Bik, Li Philip Kam-Tao, Szeto Cheuk-Chun

机构信息

Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.

出版信息

Ann Rheum Dis. 2007 Jul;66(7):886-92. doi: 10.1136/ard.2006.063123. Epub 2007 Feb 26.

Abstract

BACKGROUND

Lupus nephritis is characterised by intrarenal inflammation and lymphocyte activation.

AIM

To examine the profile of cytokine gene expression in glomerulus and tubulointerstitium in patients with lupus nephritis.

METHODS

36 consecutive patients with systemic lupus erythematosus having active renal disease were recruited, and they were required to undergo kidney biopsy. Glomerular and tubulointestitial cytokine expression of interleukin (IL)2, 4, 10, 12, 18, interferon gamma (IFN)gamma, T-bet (the Th1 transcription factor), GATA-3 (the Th2 transcription factor), transforming growth factor beta and monocyte chemoattractant protein (MCP)1 were studied by laser microdissection of the renal biopsy specimen, followed by real-time quantitative PCR.

RESULTS

There were 13 patients with World Health Organization class III nephritis, 14 patients with class IV nephritis and 9 patients with class V nephritis. There was a significant correlation between serum C3, C4 and anti-double strand DNA antibody level with glomerular expression of T-bet, IFNgamma and IL2. There was a significant correlation between histological activity index and glomerular expression of IL12, IL18, IL10 and MCP1. In addition, the degree of glomerular leucocyte infiltration significantly correlated with glomerular expression of IFNgamma, IL10, IL12 and IL18. By contrast, histological chronicity index correlated with the tubulointerstitial expression of IL2, MCP1 and GATA-3.

CONCLUSIONS

Intraglomerular expression of certain target genes correlate with the severity of systemic as well as histological activity, whereas the tubulointerstitial expression of other target genes correlate with the degree of chronic kidney scarring. This result may shed light on the immunopathogenesis of lupus nephritis.

摘要

背景

狼疮性肾炎的特征是肾内炎症和淋巴细胞活化。

目的

研究狼疮性肾炎患者肾小球和肾小管间质中细胞因子基因表达情况。

方法

招募36例患有活动性肾脏疾病的系统性红斑狼疮患者,要求他们进行肾活检。通过对肾活检标本进行激光显微切割,随后进行实时定量PCR,研究白细胞介素(IL)2、4、10、12、18、干扰素γ(IFN)γ、T-bet(Th1转录因子)、GATA-3(Th2转录因子)、转化生长因子β和单核细胞趋化蛋白(MCP)1在肾小球和肾小管间质中的细胞因子表达。

结果

有13例世界卫生组织III级肾炎患者,14例IV级肾炎患者和9例V级肾炎患者。血清C3、C4和抗双链DNA抗体水平与肾小球中T-bet、IFNγ和IL2的表达之间存在显著相关性。组织学活动指数与肾小球中IL12、IL18、IL10和MCP1的表达之间存在显著相关性。此外,肾小球白细胞浸润程度与肾小球中IFNγ、IL10、IL12和IL18的表达显著相关。相比之下,组织学慢性指数与肾小管间质中IL2、MCP1和GATA-3的表达相关。

结论

某些靶基因的肾小球内表达与全身及组织学活动的严重程度相关,而其他靶基因的肾小管间质表达与慢性肾瘢痕形成程度相关。这一结果可能有助于揭示狼疮性肾炎的免疫发病机制。

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本文引用的文献

1
Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis.狼疮性肾炎患者中Th1/Th2转录因子失衡。
Rheumatology (Oxford). 2006 Aug;45(8):951-7. doi: 10.1093/rheumatology/kel029. Epub 2006 Feb 3.
6
Cytokine balance in kidney tissue from lupus nephritis patients.狼疮性肾炎患者肾脏组织中的细胞因子平衡
Rheumatology (Oxford). 2003 Aug;42(8):935-8. doi: 10.1093/rheumatology/keg255. Epub 2003 Mar 31.
9
Predominance of Th1 immune response in diffuse proliferative lupus nephritis.弥漫性增殖性狼疮性肾炎中Th1免疫反应占主导地位。
Arthritis Rheum. 2001 Sep;44(9):2097-106. doi: 10.1002/1529-0131(200109)44:9<2097::AID-ART360>3.0.CO;2-6.

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