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

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 and 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. Limitations 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.