title: Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis.
abstract: OBJECTIVE
  To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)-positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  We screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20).
  
  
  RESULTS
  Differential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well-discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD.
  
  
  CONCLUSIONS
  While AQP4-Ab-positive and -negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS.
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Metz
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Beißbarth
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Ellenberger
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Florence
authors.initials: F
authors.lastname: Pache
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Stork
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ringelstein
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Jarius
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wildemann
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Hassan
authors.initials: H
authors.lastname: Dihazi
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: Departments of Neuropathology (I.M., L.S., W.B.), Medical Statistics (T.B., D.E., T.F.), and Nephrology and Rheumatology, Internal Medicine (H.D.), University Medical Center Göttingen; Department of Neurology (F. Pache, K.R., F. Paul) and Clinical and Experimental Multiple Sclerosis Research Center (F. Pache, K.R., F. Paul), Charité-Universitätsmedizin Berlin; NeuroCure Clinical Research Center and Experimental and Clinical Research Center (F. Pache, F. Paul), Max Delbrueck Center for Molecular Medicine; Department of Neurology (M.R., O.A.), Medical Faculty, Heinrich-Heine-University Düsseldorf; and Molecular Neuroimmunology Group, Department of Neurology (S.J., B.W.), University of Heidelberg, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul