Tubular osteopontin expression in patients with ANCA-associated glomerulonephritis

Objective: To elucidate the role of osteopontin (OPN) in monocyte recruitme nt in crescentic glomerulonephritis, we investigated immunohistochemical lo calization of OPN in the kidney and its correlation with clinical and histo pathologic parameters in biopsy specimens of patients with myeloperoxidase antineutrophil cytoplasmic autoantibody- (MPO-ANCA) associated glomerulonep hritis. Methods: Twelve patients with MPO-ANCA-associated glomerulonephriti s were enrolled in this study. Clinical parameters such as creatinine clear ance and urinary protein excretion of each patient were obtained at the tim e of biopsy. Paraffin-embedded sections were used for immunohistochemical s taining using the LSAB method. Five cortical interstitial fields randomly s elected at original magnification x 200 were assessed using a computer-assi sted color image analyzer. Tubular OPN expression was assessed as the perce ntage of positive area in the tubulointerstitium. Double immunofluorescent staining using antibodies against OPN and alphav beta (3) was performed. Re sults: In all of the cases studied, OPN was occasionally localized within t he glomeruli, and expressed slightly in proximal tubular epithelium and sig nificantly in distal tubular epithelium. Tubular OPN expression tended to b e promoted in the interstitium infiltrating by numerous monocytes/macrophag es. The extent of tubular OPN expression was positively correlated with ser um ANCA titers and urinary OPN concentrations. Enhanced alphav beta (3) exp ression appeared in the distal tubular epithelium expressing OPN. Conclusio n: These results suggest that inducible expression of OPN and alphav beta ( 3) in the tubular epithelium seems to be associated with interstitial moncy te infiltration and subsequent tubulointerstitial changes in human MPO-ANCA -associated glomerulonephritis.