title: Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  Acute disseminated encephalomyelitis (ADEM) and relapsing-remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
  
  
  METHODS
  We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles.
  
  
  RESULTS
  ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62-86%; specificity 56-79%) from MS serum (sensitivity 40-87%; specificity 62-86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides.
  
  
  CONCLUSIONS
  Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Van Haren
authors.forename: Beren H
authors.initials: BH
authors.lastname: Tomooka
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kidd
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.forename: Silvia N
authors.initials: SN
authors.lastname: Tenembaum
authors.forename: Daniela
authors.initials: D
authors.lastname: Pohl
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: David A
authors.initials: DA
authors.lastname: Hafler
authors.forename: Lawrence
authors.initials: L
authors.lastname: Steinman
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D000941:Antigens / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D015331:Cohort Studies; D003937:Diagnosis, Differential; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis* / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D055815:Young Adult
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009185:Myelin Proteins
keywords: Pediatric disease; acute disseminated encephalomyelitis; autoantibody; autoimmune disease; biomarker; differential diagnosis; immunoassay; immunoglobulin; multiple sclerosis; myelin