Neuronal and astrocytic damage in systemic lupus erythematosus patients with central nervous system involvement

Arthritis Rheum. 2003 Oct;48(10):2881-7. doi: 10.1002/art.11279.


Objective: Symptoms originating from the central nervous system (CNS) frequently occur in patients with systemic lupus erythematosus (SLE). CNS involvement in lupus is associated with increased morbidity and mortality. Currently, reliable markers for activity in this condition are absent. The goal of this study was to determine the level of the light subunit of the neurofilament triplet protein (NFL) and that of glial fibrillary acidic protein (GFAP) in the cerebrospinal fluid of SLE patients with clinically verified CNS involvement and compare them with the levels in SLE patients without CNS involvement.

Methods: We assessed cerebrospinal fluid obtained from 99 patients with SLE and 99 age-matched controls for the presence of soluble molecules indicating neuronal destruction and astrogliosis-NFL and GFAP, respectively. Patients were evaluated clinically, with magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analyses, and neuropsychiatric tests.

Results: In the group of lupus patients with CNS involvement, intrathecal levels of NFL and GFAP were increased an average of 7-fold (P </= 0.0001) and 3-fold (P </= 0.05), respectively, compared with the levels in SLE patients without overt CNS disease. Intrathecal levels of NFL correlated significantly with cerebrospinal fluid levels of interleukin-6 (IL-6) (P </= 0.005), IL-8 (P </= 0.005), pleocytosis (P </= 0.05), the albumin ratio (P </= 0.0005), and the presence of oligoclonal IgG bands (P </= 0.005). Cerebrospinal fluid levels of both NFL and GFAP also showed a significant correlation with MRI abnormalities (P </= 0.001). Successful cyclophosphamide treatment of CNS lupus resulted in significantly decreased levels of both proteins; levels of GFAP reached those observed in healthy subjects.

Conclusion: This study is the first to show biochemical signs of neuronal and astrocytic damage in patients with neuropsychiatric lupus. It is suggested that biochemical markers of brain damage should be used as a followup tool in this patient group.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytes / pathology*
  • Biomarkers / cerebrospinal fluid
  • Female
  • Glial Fibrillary Acidic Protein / cerebrospinal fluid
  • Humans
  • Interleukin-6 / cerebrospinal fluid
  • Interleukin-8 / cerebrospinal fluid
  • Lupus Vasculitis, Central Nervous System / cerebrospinal fluid*
  • Lupus Vasculitis, Central Nervous System / pathology*
  • Male
  • Middle Aged
  • Neurofilament Proteins / cerebrospinal fluid
  • Neurons / pathology*


  • Biomarkers
  • Glial Fibrillary Acidic Protein
  • Interleukin-6
  • Interleukin-8
  • Neurofilament Proteins