BACKGROUND AND 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.
BACKGROUND AND 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: Y Mikaeloff; T Moreau; M Debouverie; J Pelletier; C Lebrun; O Gout; J M Pedespan; C Van Hulle; P Vermersch; G Ponsot Journal: J Pediatr Date: 2001-09 Impact factor: 4.406
Authors: Luisa M Villar; María C Sádaba; Ernesto Roldán; Jaime Masjuan; Pedro González-Porqué; Noelia Villarrubia; Mercedes Espiño; José A García-Trujillo; Alfredo Bootello; José C Alvarez-Cermeño Journal: J Clin Invest Date: 2005-01 Impact factor: 14.808
Authors: Kevin C O'Connor; Katherine A McLaughlin; Philip L De Jager; Tanuja Chitnis; Estelle Bettelli; Chenqi Xu; William H Robinson; Sunil V Cherry; Amit Bar-Or; Brenda Banwell; Hikoaki Fukaura; Toshiyuki Fukazawa; Silvia Tenembaum; Susan J Wong; Norma P Tavakoli; Zhannat Idrissova; Vissia Viglietta; Kevin Rostasy; Daniela Pohl; Russell C Dale; Mark Freedman; Lawrence Steinman; Guy J Buckle; Vijay K Kuchroo; David A Hafler; Kai W Wucherpfennig Journal: Nat Med Date: 2007-01-12 Impact factor: 53.440
Authors: Yair Sadaka; Leonard H Verhey; Manohar M Shroff; Helen M Branson; Douglas L Arnold; Sridar Narayanan; John G Sled; Amit Bar-Or; A Dessa Sadovnick; Melissa McGowan; Ruth Ann Marrie; Brenda Banwell Journal: Ann Neurol Date: 2012-08 Impact factor: 10.422
Authors: Wolfgang Hueber; Beren H Tomooka; Franak Batliwalla; Wentian Li; Paul A Monach; Robert J Tibshirani; Ronald F Van Vollenhoven; Jon Lampa; Kazuyoshi Saito; Yoshiya Tanaka; Mark C Genovese; Lars Klareskog; Peter K Gregersen; William H Robinson Journal: Arthritis Res Ther Date: 2009-05-21 Impact factor: 5.156
Authors: W I McDonald; A Compston; G Edan; D Goodkin; H P Hartung; F D Lublin; H F McFarland; D W Paty; C H Polman; S C Reingold; M Sandberg-Wollheim; W Sibley; A Thompson; S van den Noort; B Y Weinshenker; J S Wolinsky Journal: Ann Neurol Date: 2001-07 Impact factor: 10.422
Authors: Stefanie Kuerten; Tobias V Lanz; Nithya Lingampalli; Lauren J Lahey; Christoph Kleinschnitz; Mathias Mäurer; Michael Schroeter; Stefan Braune; Tjalf Ziemssen; Peggy P Ho; William H Robinson; Lawrence Steinman Journal: Proc Natl Acad Sci U S A Date: 2020-08-18 Impact factor: 11.205
Authors: Michael Hecker; Brit Fitzner; Matthias Wendt; Peter Lorenz; Kristin Flechtner; Felix Steinbeck; Ina Schröder; Hans-Jürgen Thiesen; Uwe Klaus Zettl Journal: Mol Cell Proteomics Date: 2016-02-01 Impact factor: 5.911
Authors: Imke Metz; Tim Beißbarth; David Ellenberger; Florence Pache; Lidia Stork; Marius Ringelstein; Orhan Aktas; Sven Jarius; Brigitte Wildemann; Hassan Dihazi; Tim Friede; Wolfgang Brück; Klemens Ruprecht; Friedemann Paul Journal: Neurol Neuroimmunol Neuroinflamm Date: 2016-02-02
Authors: Patrick Peschl; Melanie Ramberger; Romana Höftberger; Karin Jöhrer; Matthias Baumann; Kevin Rostásy; Markus Reindl Journal: Int J Mol Sci Date: 2017-03-22 Impact factor: 5.923
Authors: Raymond A Sobel; Mary Jane Eaton; Prajakta Dilip Jaju; Eugene Lowry; Julian R Hinojoza Journal: J Neuropathol Exp Neurol Date: 2019-09-01 Impact factor: 3.685