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1型辅助性T细胞转录因子T-bet在狼疮患者尿沉渣中的表达可预测疾病复发。

Expression of T-bet, a type 1 T-helper cell transcription factor, in the urinary sediment of lupus patients predicts disease flare.

作者信息

Chan R W-Y, Lai F M-M, Li E K-M, Tam L-S, Chow K-M, Li P K-T, Szeto C-C

机构信息

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

出版信息

Rheumatology (Oxford). 2007 Jan;46(1):44-8. doi: 10.1093/rheumatology/kel192. Epub 2006 Jun 4.

DOI:10.1093/rheumatology/kel192
PMID:16754628
Abstract

BACKGROUND

Systemic lupus erythematosus (SLE) is characterized by the aberrant activation of T-lymphocytes. Since T-bet is the principal transcription factor for the differentiation of type-1 helper T-lymphocyte, we study the impact of urinary T-bet mRNA expression in clinically quiescent SLE patients on the risk of subsequent disease flare.

METHODS

We studied 60 quiescent SLE patients. Urinary mRNA expression of T-bet was studied by the real-time quantitative polymerase chain reaction. Patients were followed for 4 yrs for disease flare.

RESULTS

We studied 60 patients; 57 were female. The mean age was 38.8 +/- 11.2 yrs. Their baseline SLE disease activity index score was 1.63 +/- 1.64. During the follow-up, 28 patients (46.6%) developed lupus flare, of which 17 (28.3%) had severe flare. Receiver operating characteristic curves showed that urinary T-bet expression three times above the average level of healthy control had 64.3% sensitivity and 84.4% specificity of predicting all lupus flare. Using this cut-off, patients with a high urinary T-bet expression had a significantly higher risk of all lupus flare and severe flare than the patients with a low T-bet expression (log-rank test, P < 0.001 for both). With multivariate Cox proportional hazard model to adjust for potential confounding variables, urinary T-bet expression and patient's sex were the only independent predictors of all lupus flare and severe flare. It could be estimated that 1-fold increase in urinary T-bet expression would result in 8.4% excess risk of all lupus flare [95% confidence interval (CI), 4.1-13.0%, P < 0.001] and 12.9% excess risk of severe flare (95% CI 7.4-18.7%, P < 0.001).

CONCLUSIONS

A high urinary T-bet expression was an independent predictor of lupus flare. Measurement of urinary T-bet may provide valuable information for the risk stratification of SLE patients.

摘要

背景

系统性红斑狼疮(SLE)的特征是T淋巴细胞异常激活。由于T-bet是1型辅助性T淋巴细胞分化的主要转录因子,我们研究了临床静止期SLE患者尿T-bet mRNA表达对随后疾病复发风险的影响。

方法

我们研究了60例静止期SLE患者。通过实时定量聚合酶链反应研究尿T-bet的mRNA表达。对患者进行4年的随访以观察疾病复发情况。

结果

我们研究了60例患者,其中57例为女性。平均年龄为38.8±11.2岁。他们的基线SLE疾病活动指数评分为1.63±1.64。在随访期间,28例患者(46.6%)出现狼疮复发,其中17例(28.3%)为严重复发。受试者工作特征曲线显示,尿T-bet表达高于健康对照平均水平3倍时,预测所有狼疮复发的敏感性为64.3%,特异性为84.4%。采用此临界值,尿T-bet表达高的患者发生所有狼疮复发和严重复发的风险显著高于尿T-bet表达低的患者(对数秩检验,两者P均<0.001)。通过多变量Cox比例风险模型调整潜在混杂变量后,尿T-bet表达和患者性别是所有狼疮复发和严重复发的唯一独立预测因素。据估计,尿T-bet表达增加1倍会导致所有狼疮复发的额外风险增加8.4%[95 %置信区间(CI),4.1 - 13.0%,P < 0.001],严重复发的额外风险增加12.9%(95 % CI 7.4 - 18.7%,P < 0.001)。

结论

尿T-bet高表达是狼疮复发的独立预测因素。检测尿T-bet可为SLE患者的风险分层提供有价值的信息。

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