title: Cerebrospinal fluid levels of a proliferation-inducing ligand (APRIL) are increased in patients with neuropsychiatric systemic lupus erythematosus.
abstract: OBJECTIVE
  A proliferation-inducing ligand (APRIL) and B-cell activation factor (BAFF) are B-cell stimulation and survival molecules. We have investigated whether APRIL and/or BAFF activity is enhanced in the systemic and/or intrathechal compartment of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). In particular, the association between fatigue and APRIL/BAFF activity was investigated.
  
  
  METHODS
  Twenty-eight NPSLE patients were evaluated clinically, with sampling of cerebrospinal fluid (CSF) and blood, and magnetic resonance imaging (MRI). CSF and blood samples from 13 multiple sclerosis (MS) patients and 17 patients with other neurological diseases (OND) were used as controls. Protein levels of BAFF and APRIL were quantified in CSF and plasma, mRNA expression levels of BAFF and APRIL were determined in peripheral blood (PBMC) and CSF mononuclear cells (CSF-MC). The Fatigue Severity Scale (FSS) was used to quantify the degree of fatigue.
  
  
  RESULTS
  NPSLE patients had higher levels of APRIL in CSF as compared to OND (p < 0.01). No corresponding increase in APRIL mRNA levels was detected in CSF-MC. BAFF levels in plasma were higher in NPSLE than in OND (p < 0.001). BAFF mRNA expression in PBMC was also higher in NPSLE patients than in controls (p < 0.05). FSS scores in patients with NPSLE correlated significantly with APRIL levels in CSF.
  
  
  CONCLUSIONS
  Protein levels of APRIL in CSF were increased in NPSLE as compared to OND. Moreover, there was a positive correlation between CSF APRIL levels and fatigue. Our results suggest that APRIL and possibly also BAFF may be involved in the pathogenesis of NPSLE and in SLE-related fatigue.
authors.affiliation: Division of Neurology, Karolinska Institutet, Karolinska University Hospital (Solna), Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Hopia
authors.forename: M
authors.initials: M
authors.lastname: Thangarajh
authors.forename: M
authors.initials: M
authors.lastname: Khademi
authors.forename: A
authors.initials: A
authors.lastname: Laveskog
authors.forename: E
authors.initials: E
authors.lastname: Wallström
authors.forename: E
authors.initials: E
authors.lastname: Svenungsson
authors.forename: M
authors.initials: M
authors.lastname: Andersson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000097:blood / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005221:Fatigue / Q000097:blood / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D020945:Lupus Vasculitis, Central Nervous System / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood / Q000134:cerebrospinal fluid*; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13