title: Antigen microarrays identify CNS-produced autoantibodies in RRMS.
abstract: OBJECTIVE
  Multiple sclerosis (MS) is characterized by the local production of antibodies in the CNS and the presence of oligoclonal bands in the CSF. Antigen arrays allow the study of antibody reactivity against a large number of antigens using small volumes of fluid with greater sensitivity than ELISA. We investigated whether there were unique autoantibodies in the CSF of patients with MS as measured by antigen arrays and whether these antibodies differed from those in serum.
  
  
  METHODS
  We used antigen arrays to analyze the reactivity of antibodies in matched serum and CSF samples of 20 patients with untreated relapsing-remitting MS (RRMS), 26 methylprednisolone-treated patients with RRMS, and 20 control patients with other noninflammatory neurologic conditions (ONDs) against 334 different antigens including heat shock proteins, lipids, and myelin antigens.
  
  
  RESULTS
  We found different antibody signatures in matched CSF and serum samples The targets of these antibodies included epitopes of the myelin antigens CNP, MBP, MOBP, MOG, and PLP (59%), HSP60 and HSP70 (38%), and the 68-kD neurofilament (3%). The antibody response in patients with MS was heterogeneous; CSF antibodies in individual patients reacted with different autoantigens. These autoantibodies were locally synthesized in the CNS and were of the immunoglobulin G class. Finally, we found that treatment with steroids decreased autoantibody reactivity, epitope spreading, and intrathecal autoantibody synthesis.
  
  
  CONCLUSIONS
  These studies provide a new avenue to investigate the local antibody response in the CNS, which may serve as a biomarker to monitor both disease progression and response to therapy in MS.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. fquintana@rics.bwh.harvard.edu
authors.forename: F J
authors.initials: FJ
authors.lastname: Quintana
authors.forename: M F
authors.initials: MF
authors.lastname: Farez
authors.forename: G
authors.initials: G
authors.lastname: Izquierdo
authors.forename: M
authors.initials: M
authors.lastname: Lucas
authors.forename: I R
authors.initials: IR
authors.lastname: Cohen
authors.forename: H L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology; D043025:Oligoclonal Bands / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D040081:Protein Array Analysis
chemical_list: D001323:Autoantibodies; D043025:Oligoclonal Bands