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.
Chan
R W-Y
RW
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Lai
F M-M
FM
Li
E K-M
EK
Tam
L-S
LS
Chow
K-M
KM
Li
P K-T
PK
Szeto
C-C
CC
D000328:Adult; D015415:Biomarkers / Q000652:urine; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000652:urine*; D008181:Lupus Nephritis / Q000652:urine; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012720:Severity of Illness Index; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000652:urine*; D015854:Up-Regulation; D000098815:T-bet Transcription Factor
D015415:Biomarkers; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor