title: Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production.
abstract: BACKGROUND
  Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS-associated autoantibodies.
  
  
  OBJECTIVE
  To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels.
  
  
  RESULTS
  Twenty-three patients with relapsing-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p<0.009) and MS severity score (p<0.05), but not with disease activity as determined by the number of gadolinium-enhanced lesions. The patients were followed for up to 26 months, during which the BAFF levels remained elevated without association to increased disease activity. IFN-beta therapy caused an increase in plasma BAFF levels after both 3 and 6 months of therapy (p<0.002). However, an 11% decrease in IgM and a 33% decrease in IgG anti-MBP autoantibodies (p<0.09 and p<0.009, respectively) was observed after 6 months.
  
  
  CONCLUSIONS
  Pre-treatment BAFF levels correlate with high disability scores in MS, suggesting that high BAFF expression is a negative prognostic marker. Despite its known beneficial effects, IFN-beta therapy causes a sustained increase in plasma BAFF levels, which does not translate into increased levels of anti-MBP autoantibodies.
authors.affiliation: Institute for Inflammation Research, Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hedegaard
authors.forename: Finn
authors.initials: F
authors.lastname: Sellebjerg
authors.forename: Martin
authors.initials: M
authors.lastname: Krakauer
authors.forename: Dan
authors.initials: D
authors.lastname: Hesse
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D053264:B-Cell Activating Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003718:Denmark; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015415:Biomarkers; D007155:Immunologic Factors; C499048:MBP protein, human; D004676:Myelin Basic Protein; C505719:TNFSF13B protein, human; D016899:Interferon-beta; D000068556:Interferon beta-1a