Activation of the signal transducer and activator of transcription-1 in diffuse proliferative lupus nephritis

Abstract

Difuse proliferative lupus nephritis (DPLN) is the most common and severe form of lupus nephritis. A predominance of IFN-gamma-producing T cells in both peripheral and renal tissues of patients with DPLN has been identified which suggests an important role for cell-mediated immunity in the pathogenesis of this complication in SLE. The biological effects of IFN-gamma rely mainly on the activity of the transcription factor called signal transducer and activator of transcription (STAT)-1. To assess the IFN-gamma/STAT-1 pathway in DPLN, we examined the expression of STAT-1 in renal biopsies from 15 DPLN patients by immunohistochemical staining with an anti-STAT-1 antibody. The expression of STAT-1 in renal tissues was correlated with several clinical and laboratory findings in these DNPN patients.STAT-1 was activated in the tubular cells in all DPLN patients. Seven of 15 DPLN biopsies (46.7%) showed positive cells in glomeruli. Five of these seven DPLN biopsies (71.4%) with positive glomerular cells showed a serum creatinine >1.5 mg/mL at the time the biopsy was carried out whereas only one of eight DPLN biopsy specimens (12.5%) without positive glomerular cells, showed a serum creatinine >1.5 mg/mL (P = 0.041). Moreover, the percentage of DPLN patients with a worse renal outcome in those who showed expression of STAT-1 in glomerulari were higher in comparison to those without STAT-1 expression (P = 0.041). Our results show that STAT-1 is activated in DPLN suggesting that biological effects of IFN-gamma in renal tissues depend, at least in part, on the activation of STAT-1.