AbstractObjectiveTo determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX3CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage.MethodsLevels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme‐linked immunosorbent assay. Expression of Fkn and CX3CR1 was quantified using real‐time polymerase chain reaction. Surface expression of CX3CR1 on peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively.ResultsSerum sFkn levels were significantly higher in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls. In addition, significant correlations between serum sFkn levels and the SLEDAI, the SLICC/ACR Damage Index, anti–double‐stranded DNA and anti‐Sm antibody titers, immune complex levels (C1q), and serum complement levels (CH50) were observed. Expression of CX3CR1 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 untreated patients with newly diagnosed NPSLE than in SLE patients without neuropsychiatric involvement; treatment reduced both serum and CSF levels of sFkn in patients with SLE.ConclusionSoluble Fkn and CX3CR1 may play key roles in the pathogenesis of SLE, including the neuropsychiatric involvement. Soluble Fkn is also a serologic marker of disease activity and organ damage in patients with SLE, and its measurement in CSF may be useful for the diagnosis of NPSLE and followup of patients with NPSLE.