title: Elevated levels of soluble fractalkine in active systemic lupus erythematosus: potential involvement in neuropsychiatric manifestations.
abstract: OBJECTIVE
  To determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX(3)CR1, 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.
  
  
  METHODS
  Levels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified using real-time polymerase chain reaction. Surface expression of CX(3)CR1 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.
  
  
  RESULTS
  Serum 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 CX(3)CR1 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.
  
  
  CONCLUSIONS
  Soluble Fkn and CX(3)CR1 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.
authors.affiliation: Showa University School of Medicine, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yajima
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kasama
authors.forename: Takeo
authors.initials: T
authors.lastname: Isozaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Odai
authors.forename: Mizuho
authors.initials: M
authors.lastname: Matsunawa
authors.forename: Masao
authors.initials: M
authors.lastname: Negishi
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ide
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kameoka
authors.forename: Shunsei
authors.initials: S
authors.lastname: Hirohata
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Adachi
mesh_terms: D000328:Adult; D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology*; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D019707:Receptors, Chemokine