Rheumatology Advance Access originally published online on February 3, 2006
Rheumatology 2006 45(8):951-957; doi:10.1093/rheumatology/kel029
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Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis
Department of Medicine and Therapeutics 1 Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Correspondence to: C.-C. Szeto, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. E-mail: ccszeto{at}cuhk.edu.hk
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.
KEY WORDS: SLE, Lupus nephritis, T-bet, GATA-3
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