title: Antigen microarrays identify unique serum autoantibody signatures in clinical and pathologic subtypes of multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic relapsing disease of the central nervous system (CNS) in which immune processes are believed to play a major role. To date, there is no reliable method by which to characterize the immune processes and their changes associated with different forms of MS and disease progression. We performed antigen microarray analysis to characterize patterns of antibody reactivity in MS serum against a panel of CNS protein and lipid autoantigens and heat shock proteins. Informatic analysis consisted of a training set that was validated on a blinded test set. The results were further validated on an independent cohort of relapsing-remitting (RRMS) samples. We found unique autoantibody patterns that distinguished RRMS, secondary progressive (SPMS), and primary progressive (PPMS) MS from both healthy controls and other neurologic or autoimmune driven diseases including Alzheimer's disease, adrenoleukodystropy, and lupus erythematosus. RRMS was characterized by autoantibodies to heat shock proteins that were not observed in PPMS or SPMS. In addition, RRMS, SPMS, and PPMS were characterized by unique patterns of reactivity to CNS antigens. Furthermore, we examined sera from patients with different immunopathologic patterns of MS as determined by brain biopsy, and we identified unique antibody patterns to lipids and CNS-derived peptides that were linked to each type of pathology. The demonstration of unique serum immune signatures linked to different stages and pathologic processes in MS provides an avenue to monitor MS and to characterize immunopathogenic mechanisms and therapeutic targets in the disease.
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Quintana
authors.forename: Mauricio F
authors.initials: MF
authors.lastname: Farez
authors.forename: Vissia
authors.initials: V
authors.lastname: Viglietta
authors.forename: Antonio H
authors.initials: AH
authors.lastname: Iglesias
authors.forename: Yifat
authors.initials: Y
authors.lastname: Merbl
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
authors.forename: Alexandre S
authors.initials: AS
authors.lastname: Basso
authors.forename: Samia J
authors.initials: SJ
authors.lastname: Khoury
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.forename: Irun R
authors.initials: IR
authors.lastname: Cohen
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods*; D009103:Multiple Sclerosis / Q000097:blood* / Q000145:classification / Q000276:immunology* / Q000503:physiopathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044967:Serum / Q000276:immunology
chemical_list: D001323:Autoantibodies; D002784:Cholesterol