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Elevated Levels of Fractalkine Expression and Accumulation of CD16+ Monocytes in Glomeruli of Active Lupus Nephritis

Abstract

BACKGROUND: Fractalkine (Fkn) is a chemokine that affects cells expressing its receptor, CX3CR1, including CD16-positive (CD16+) monocytes/macrophages (CD16+ Mos). The relationship of levels of glomerular Fkn expression and infiltration by CD16+ Mos with the severity and diversity of glomerular lesions in human lupus nephritis is not known. STUDY DESIGN: Retrospective cross-sectional analysis of variables observed in biopsy specimens. SETTINGS & PARTICIPANTS: 88 patients with systemic lupus erythematosus. PREDICTOR: Histological class and severity of lupus nephritis according to the International Society of Nephrology/Renal Pathology Society and clinicopathologic factors. OUTCOMES: Outcome variables are assays related to the degree of glomerular Fkn expression an CD16+ Mo infiltration. MEASUREMENTS: Immunohistological grading of Fkn staining, number of CD16+ Mos, and messenger RNA levels of Fkn and CD16 in glomeruli. RESULTS: Patients with proliferative lupus nephritis (class III and IV glomeruli) showed significantly greater glomerular Fkn expression and CD16+ Mo counts than those with other classes. Infiltrating CD16+ Mos within glomeruli expressed CX3CR1. Moreover, glomerular Fkn expression significantly correlated with the histopathologic activity index and CD16+ Mo counts, and CD16+ Mo counts significantly correlated with serum levels of blood urea nitrogen, complement (CH50), and anti-DNA antibody; estimated glomerular filtration rate; and urinary protein excretion. Glucocorticoid therapy had a tendency to decrease both glomerular Fkn expression and CD16+ Mo counts. LIMITAIONS: Only frozen biopsy specimens (from 49 patients) were analyzed for the evaluation of glomerular Fkn Expression. CONCLUSION: Disease activity and proliferative glomerular lupus nephritis lesions are associated with the glomerular Fkn expression and CD16+ Mo accumulation.

Authors: Yoshimoto S, Nakatani K, Iwano M, Asai O, Sameljima K, Sakan H, Terada M, Harada K, Akai Y, Shiiki H, Nose M, Saito Y
Journal: Am J Kidney Dis., 50(1): 47-58
Year: 2007
PubMed: Find in PubMed