CD44 expression in serum and kidney correlates with disease activity in lupus nephritis

Abstract

INTRODUCTION AND AIMS: Lupus nephritis is characterized by a loss of immune tolerance to self-antigens leading to immune-mediated kidney injury. CD44 is a cell surface receptor for hyaluronan and has been implicated in tissue inflammation and fibrosis. We investigated serum CD44 level and its renal expression in human and murine lupus nephritis, focusing on its role in renal fibrosis. METHODS: Serum CD44 was measured in paired sera from 56 patients with biopsy-proven diffuse proliferative lupus nephritis, during active disease and remission respectively, using a commercially available ELISA. Healthy subjects (n=36) and patients with non-lupus glomerular diseases (n=37) were included as controls. CD44 expression in human lupus nephritis kidney biopsies and NZBWF1/J mice was assessed using cytochemical staining. Mesangial cells were isolated from NZBWF1/J mice to investigate the mechanism of CD44 synthesis. RESULTS: Serum CD44 levels were significantly higher during active lupus nephritis compared to levels in the same patients during remission, glomerular disease controls, and healthy subjects (P<0.001 for all). Serum CD44 level in lupus nephritis patients correlated with the level of anti-dsDNA antibodies (r=0.43, P<0.001) and serum creatinine (r=0.46, P<0.0001), and inversely correlated with C3 level (r=-0.45, P<0.001). Active lupus nephritis kidney biopsies showed strong CD44 staining in both resident renal cells and infiltrating cells in glomeruli and renal tubules, while minimal CD44 expression was observed in healthy kidney tissue. Renal cortical CD44 mRNA expression increased with progressive disease and renal fibrosis in NZBWF1/J mice. In vitro experiments showed constitutive CD44 expression in mesangial cells from NZBWF1/J mice, and exogenous hyaluronan, IL-6, IL-1β, TNF-α induced an increase in CD44 synthesis. CONCLUSIONS: Our data suggest that CD44 is involved in the pathogenesis of renal inflammation and fibrosis in lupus nephritis. © The Author 2015.