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

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.

Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is characterized by the aberrant activation of T lymphocytes. Since T-bet and GATA-3 are the principal transcription factors for the differentiation of type-1 and type-2 helper T lymphocytes, respectively, we studied their mRNA expression in the urinary sediment of SLE patients and compared this with their urinary and intra-renal protein expression. METHODS: We studied 100 SLE patients and 10 healthy subjects. Urinary mRNA expression of T-bet and GATA-3 were studied by the real-time quantitative polymerase chain reaction. Intra-renal and urinary expressions of T-bet and GATA-3 were studied by immunohistochemistry and western blotting, respectively. RESULTS: The urinary mRNA and protein expressions of T-bet were significantly higher in SLE patients with active nephritis than those with inactive disease (mRNA: P < 0.001; protein: P = 0.004). The urinary mRNA expression of T-bet correlated with the SLE disease activity index (SLEDAI) score (r = 0.55, P < 0.001) and the histological activity index (r = 0.48, P = 0.03). On the other hand, the urinary mRNA and protein expressions of GATA-3 were significantly lower in SLE patients with active nephritis (mRNA: P < 0.001; protein: P = 0.006), and GATA-3 mRNA expression inversely correlated with the SLEDAI score (r = 0.38, P < 0.001). For the 22 SLE patients with kidney biopsy, tubular expressions of T-bet and GATA-3 significantly correlated with the histological activity index (T-bet: r = 0.57, P = 0.006; GATA-3: r = -0.79, P < 0.001). CONCLUSIONS: Patients with active lupus nephritis have increased T-bet and depressed GATA-3 expression in the urinary sediment and kidney tissue, indicating a predominant Th1 type of T-lymphocyte activation.