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.