Abstract
Fractalkine (FKN, CX3CL1) is a membrane-bound chemokine with a domain which can induce both adhesion and migration of leukocytes and is involved in the recruitment of cells into tissues undergoing inflammatory responses. Since FKN is expressed in many tissues but at particularly high levels in the brain, we hypothesized that FKN and its specific receptor CX3CR1 may be implicated in the pathogenesis of systemic lupus erythematosus (SLE), especially of SLE with neuropsychiatric involvement (NPSLE) . The aim of this study is to determine soluble FKN (sFKN) levels in SLE and to assess their relationship with disease activity and damage. Soluble FKN levels in serum and cerebrospinal fluid (CSF) were measured by ELISA. The expression of FKN and CX3CR1 was quantified using real-time PCR. The surface expression of CX3CR 1 on peripheral blood mononuclear cells (PBMCs) was determined flow cytometrically. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC/ACR DI), respectively. Serum sFKN levels were significantly higher in SLE patients than in rheumatoid arthritis (RA) patients or healthy con trols, and there were significant correlations between serum sFKN levels and SLEDAI, SLICC/ ACR DI, anti-ds DNA and anti-Sm antibody titers, immune complex levels (IC-C1q) and serum complement levels (CH50) . The expression of CX3CR 1 was significantly greater in PBMCs from patients with active SLE than in those from RA patients or healthy controls. Levels of sFKN were also significantly higher in CSF from newly-diagnosed, untreated NPSLE patients than in SLE patients without neuropsychiatric involvement ; treatment significantly reduced both CSF and serum sFKN levels in NPSLE patients. FKN and CX3CR1 play key roles in the pathogenesis of SLE including neuropsychiatric involvement. Soluble FKN is also a serologic marker of disease activity and organ damage in SLE patients, and its measurement in CSF may be useful for diagnosis and follow-up of NPSLE patients.
