Glomerular cell apoptosis in human lupus nephritis

Disturbed apoptosis is proposed to be involved in the pathogenesis of systemic lupus erythematosus. However, the role of renal cell apoptosis in the pathogenesis and progression of human lupus nephritis is still controversial. We have investigated glomerular cell apoptosis and the clinicopathological relationship between apoptosis and immunoserological or histological findings in 22 patients with lupus nephritis using electron microscopy and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Resident glomerular cells as well as infiltrating neutrophils undergoing apoptosis were observed in 12 of 20 patients with lupus nephritis using electron microscopy. TUNEL-positive cells were recognized in 93% of patients with diffuse proliferative lupus nephritis (class IV) in contrast to the 20% of patients with class V. The number of TUNEL-positive cells in glomeruli significantly correlated with the level of immunoserological activity of lupus, such as anti-double-stranded DNA autoantibody and consumption of plasma complement. There was a positive correlation between glomerular cell apoptosis and the degree of proliferation in lupus nephritis. These data suggest that apoptosis is increased, but not decreased in glomeruli from patients with lupus nephritis. The signals that could induce glomerular cell apoptosis in lupus nephritis will need to be identified.