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

Autoimmune Diseases Research Lab, Vall d'Hebron Research Institute, Barcelona, Spain

J. Ordi-Ros

Autoimmune Diseases Research Lab, Vall d'Hebron Research Institute, Barcelona, Spain, jordi{at}vhebron.net

E. Balada

Autoimmune Diseases Research Lab, Vall d'Hebron Research Institute, Barcelona, Spain

A. Segarra-Medrano

Department of Nephrology, Hospital Vall d'Hebron, Barcelona, Spain

J. Majó-Masferrer

Department of Pathology, Hospital Vall d'Hebron, Barcelona, Spain

M. Labrador-Horrillo

Autoimmune Diseases Research Lab, Vall d'Hebron Research Institute, Barcelona, Spain

M. Vilardell-Tarrés

Autoimmune Diseases Research Lab, Vall d'Hebron Research Institute, Barcelona, Spain

Difuse proliferative lupus nephritis (DPLN) is the most common and severe form of lupus nephritis. A predominance of IFN--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- rely mainly on the activity of the transcription factor called signal transducer and activator of transcription (STAT)-1. To assess the IFN-/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- in renal tissues depend, at least in part, on the activation of STAT-1. Lupus (2007) 16, 483—488.

Key Words: lupus nephritis • renal biopsy • STAT-1

Lupus, Vol. 16, No. 7, 483-488 (2007)
DOI: 10.1177/0961203307079618


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