Implication of perturbed axoglial apparatus in early pediatric multiple sclerosis†
Ajit Singh Dhaunchak PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorChristopher Becker PhD
PPD Biomarker Discovery, Inc and Caprion Proteomics, Menlo Park, CA
Search for more papers by this authorHoward Schulman PhD
PPD Biomarker Discovery, Inc and Caprion Proteomics, Menlo Park, CA
Search for more papers by this authorOmar De Faria Jr MSc
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorSathyanath Rajasekharan PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Search for more papers by this authorBrenda Banwell MD
Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
Search for more papers by this authorDavid R. Colman PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorCorresponding Author
Amit Bar-Or MD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Neuroimmunology Unit and Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and the McGill University Health Centre, 3801 University Street, Room 111, Montreal, Quebec, H3A2B4, CanadaSearch for more papers by this authoron behalf of the Canadian Pediatric Demyelinating Disease Group
Search for more papers by this authorAjit Singh Dhaunchak PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorChristopher Becker PhD
PPD Biomarker Discovery, Inc and Caprion Proteomics, Menlo Park, CA
Search for more papers by this authorHoward Schulman PhD
PPD Biomarker Discovery, Inc and Caprion Proteomics, Menlo Park, CA
Search for more papers by this authorOmar De Faria Jr MSc
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorSathyanath Rajasekharan PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Search for more papers by this authorBrenda Banwell MD
Neuroscience and Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada
Search for more papers by this authorDavid R. Colman PhD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Program in NeuroEngineering of McGill University, Montreal, Quebec, Canada
Search for more papers by this authorCorresponding Author
Amit Bar-Or MD
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and McGill University Health Centre, Montreal, Quebec, Canada
Neuroimmunology Unit and Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University and the McGill University Health Centre, 3801 University Street, Room 111, Montreal, Quebec, H3A2B4, CanadaSearch for more papers by this authoron behalf of the Canadian Pediatric Demyelinating Disease Group
Search for more papers by this authorMembers of the Canadian Pediatric Demyelinating Disease Network are listed in the Appendixat the end of this article.
Abstract
Cerebrospinal fluid samples collected from children during initial presentation of central nervous system inflammation, who may or may not subsequently be diagnosed as having multiple sclerosis (MS), were subjected to large-scale proteomics screening. Unexpectedly, major compact myelin membrane proteins typically implicated in MS were not detected. However, multiple molecules that localize to the node of Ranvier and the surrounding axoglial apparatus membrane were implicated, indicating perturbed axon–glial interactions in those children destined for diagnosis of MS. Ann Neurol 2012;
Supporting Information
Additional supporting information can be found in the online version of this article.
| Filename | Description |
|---|---|
| ANA_22693_sm_SuppFig.doc548.5 KB | Supporting Information |
| ANA_22693_sm_SuppTab1.xls6.9 MB | Supporting Information |
| ANA_22693_sm_SuppTab2.doc57 KB | Supporting Information |
| ANA_22693_sm_SuppTab3.doc29.5 KB | Supporting Information |
| ANA_22693_sm_SuppTab4.doc34.5 KB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1 Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008; 31: 247–269.
- 2
Lassmann H.
Experimental autoimmune encephalomyelitis. In:
AL Robert, Griffin JW, Lassman H, Nave KA, Miller R, Trapp BD.
Myelin biology and disorders.
San Diego, CA:
Academic Press,
2004:
1039–1071.
10.1016/B978-012439510-7/50096-6 Google Scholar
- 3 Tumani H, Hartung HP, Hemmer B, et al. Cerebrospinal fluid biomarkers in multiple sclerosis. Neurobiol Dis 2009; 35: 117–127.
- 4 Awad A, Hemmer B, Hartung HP, et al. Analyses of cerebrospinal fluid in the diagnosis and monitoring of multiple sclerosis. J Neuroimmunol 2010; 219: 1–7.
- 5 Ghezzi A. Clinical characteristics of multiple sclerosis with early onset. Neurol Sci 2004; 25( suppl 4): S336–S339.
- 6 Banwell B, Ghezzi A, Bar-Or A, et al. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007; 6: 887–902.
- 7 Banwell B, Bar-Or A, Arnold DL, et al. Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study. Lancet Neurol 2011; 10: 436–445.
- 8 Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria.” Ann Neurol 2005; 58: 840–846.
- 9 Wang W, Zhou H, Lin H, et al. Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards. Anal Chem 2003; 75: 4818–4826.
- 10 Krokhin OV, Craig R, Spicer V, et al. An improved model for prediction of retention times of tryptic peptides in ion pair reversed-phase HPLC: its application to protein peptide mapping by off-line HPLC-MALDI MS. Mol Cell Proteomics 2004; 3: 908–919.
- 11 Becker CH, Kumar P, Jones T, Lin H. Nonparametric mass calibration using hundreds of internal calibrants. Anal Chem 2007; 79: 1702–1707.
- 12 Tait S, Gunn-Moore F, Collinson JM, et al. An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J Cell Biol 2000; 150: 657–666.
- 13 Bernier L, Alvarez F, Norgard EM, et al. Molecular cloning of a 2′,3′-cyclic nucleotide 3′-phosphodiesterase: mRNAs with different 5′ ends encode the same set of proteins in nervous and lymphoid tissues. J Neurosci 1987; 7: 2703–2710.
- 14 Salzer JL, Holmes WP, Colman DR. The amino acid sequences of the myelin-associated glycoproteins: homology to the immunoglobulin gene superfamily. J Cell Biol 1987; 104: 957–965.
- 15 Pedraza L, Fidler L, Staugaitis SM, Colman DR. The active transport of myelin basic protein into the nucleus suggests a regulatory role in myelination. Neuron 1997; 18: 579–589.
- 16 Dhaunchak AS, Nave KA. A common mechanism of PLP/DM20 misfolding causes cysteine-mediated endoplasmic reticulum retention in oligodendrocytes and Pelizaeus-Merzbacher disease. Proc Natl Acad Sci U S A 2007; 104: 17813–17818.
- 17 Dhaunchak AS, Huang JK, De Faria OJr, et al. A proteome map of axoglial specializations isolated and purified from human central nervous system. Glia 2010; 58: 1949–1960.
- 18 Susuki K, Rasband MN. Molecular mechanisms of node of Ranvier formation. Curr Opin Cell Biol 2008; 20: 616–623.
- 19 Huang JK, Phillips GR, Roth AD, et al. Glial membranes at the node of Ranvier prevent neurite outgrowth. Science 2005; 310: 1813–1817.
- 20 Neuteboom RF, Boon M, Catsman Berrevoets CE, et al. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 2008; 71: 967–973.
- 21 Chiasserini D, Di Filippo M, Candeliere A, et al. CSF proteome analysis in multiple sclerosis patients by two-dimensional electrophoresis. Eur J Neurol 2008; 15: 998–1001.
- 22 Nie DY, Ma QH, Law JW, et al. Oligodendrocytes regulate formation of nodes of Ranvier via the recognition molecule OMgp. Neuron Glia Biol 2006; 2: 151–164.
- 23 Feinberg K, Eshed-Eisenbach Y, Frechter S, et al. A glial signal consisting of gliomedin and NrCAM clusters axonal Na+ channels during the formation of nodes of Ranvier. Neuron 2010; 65: 490–502.
- 24 Zonta B, Tait S, Melrose S, et al. Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system. J Cell Biol 2008; 181: 1169–1177.
- 25 Derfuss T, Parikh K, Velhin S, et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci U S A 2009; 106: 8302–8307.
- 26 Mathey EK, Derfuss T, Storch MK, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury. J Exp Med 2007; 204: 2363–2372.
- 27 Howell OW, Palser A, Polito A, et al. Disruption of neurofascin localization reveals early changes preceding demyelination and remyelination in multiple sclerosis. Brain 2006; 129( pt 12): 3173–3185.
- 28 Rothbard JB, Zhao X, Sharpe O, et al. Chaperone activity of α B-crystallin is responsible for its incorrect assignment as an autoantigen in multiple sclerosis. J Immunol 2011; 186: 4263–4268.
- 29 van Noort JM, Bsibsi M, Gerritsen WH, et al. Alphab-crystallin is a target for adaptive immune responses and a trigger of innate responses in preactive multiple sclerosis lesions. J Neuropathol Exp Neurol 2010; 69: 694–703.
- 30 Krupp LB, Banwell B, Tenembaum S. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68: S7–S12.
Citing Literature
