Serum and intra-renal CD44 levels correlate with disease activity in patients with lupus nephritis

Abstract

Lupus nephritis is a severe manifestation of systemic lupus erythematosus and often portends poor prognosis. CD44 is a cell surface receptor for hyaluronan and is involved in lymphocyte activation and extravasation, and tissue inflammation. We investigated serum CD44 level and its renal expression during lupus nephritis. Serum CD44 level was measured in paired sera obtained during active disease and remission respectively from patients with biopsy-proven severe proliferative lupus nephritis using ELISA. Controls included patients with non-lupus glomerular diseases and healthy subjects. CD44 expression in human lupus nephritis kidney biopsies and NZBWF1 mice was assessed by cytochemical staining. Mesangial cells were isolated from NZBWF1 mice to investigate the mechanism of CD44 synthesis. Serum CD44 levels were significantly higher during active lupus nephritis compared with remission samples, the non-lupus glomerular disease group and healthy subjects (P< 0.001 for all). In lupus nephritis patients, serum CD44 level correlated with that of anti-dsDNA antibody (r=0.43, P< 0.001) and creatinine (r=0.46, P< 0.0001), and inversely correlated with C3 (r=-0.45, P< 0.001). Strong CD44 staining was observed in infiltrating and resident renal cells in glomeruli and renal tubules in human and murine active lupus nephritis renal specimens. In contrast, minimal CD44 expression was observed in healthy kidney tissue. CD44 was constitutively expressed in cultured NZBWF1 mice mesangial cells, and its expression was significantly induced after adding exogenous hyaluronan, IL-6, IL-1β and TNF-α. Our data suggest that CD44 contributes to the pathogenesis of lupus nephritis through its effect on both infiltrating inflammatory cells and resident kidney cells.