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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents



  history
ID: 432448.0, MPI für Neurobiologie / Neuroimmunology
Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals
Authors:Derfuss, T.; Parikh, K.; Velhin, S.; Braun, M.; Mathey, E.; Krumbholz, M.; Kümpfel, T.; Moldenhauer, A.; Rader, C.; Sonderegger, P.; Pöllmann, W.; Tiefenthaller, C.; Bauer, J.; Lassmann, H.; Wekerle, H.; Karagogeos, D.; Hohlfeld, R.; Linington, C.; Meinl, E.
Language:English
Date of Publication (YYYY-MM-DD):2009-05-19
Title of Journal:Proceedings of the National Academy of Sciences of the United States of America
Journal Abbrev.:Proc. Natl. Acad. Sci. U. S. A.
Volume:106
Issue / Number:20
Start Page:8302
End Page:8307
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Gray matter pathology is increasingly recognized as an important feature of multiple sclerosis (MS), but the nature of the immune response that targets the gray matter is poorly understood. Starting with a proteomics approach, we identified contactin-2/transiently expressed axonal glycoprotein 1 (TAG-1) as a candidate autoantigen recognized by both autoantibodies and T helper (Th) 1/Th17 T cells in MS patients. Contactin-2 and its rat homologue, TAG-1, are expressed by various neuronal populations and sequestered in the juxtaparanodal domain of myelinated axons both at the axonal and myelin sides. The pathogenic significance of these autoimmune responses was then explored in experimental autoimmune encephalitis models in the rat. Adoptive transfer of TAG-1-specific T cells induced encephalitis characterized by a preferential inflammation of gray matter of the spinal cord and cortex. Cotransfer of TAG-1-specific T cells with a myelin oligodendrocyte glycoprotein-specific mAb generated focal perivascular demyelinating lesions in the cortex and extensive demyelination in spinal cord gray and white matter. This study identifies contactin-2 as an autoantigen targeted by T cells and autoantibodies in MS. Our findings suggest that a contactin-2-specific T-cell response contributes to the development of gray matter pathology.
Free Keywords:cortical pathology; experimental autoimmune encephalitis; Th1/Th17 T cells; node of Ranvier; myelin glycoproteins
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)/Clinical Neuroimmunology (Hohlfeld)
MPI für Neurobiologie/Neuroimmunology (Wekerle)
External Affiliations:[Derfuss, Tobias; Krumbholz, Markus; Kuempfel, Tania; Hohlfeld, Reinhard; Meinl, Edgar] Univ Munich, Inst Clin Neuroimmunol, D-81377 Munich, Germany.; [Parikh, Khyati; Mathey, Emily; Linington, Christopher] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland.; [Moldenhauer, Anja] Charite Univ Med Berlin, Inst Transfus Med, D-13353 Berlin, Germany.; [Rader, Christoph; Sonderegger, Peter] Univ Zurich, Inst Biochem, CH-8057 Zurich, Switzerland.; [Poellmann, Walter] Multiple Sklerose Klin, D-82335 Berg, Germany.; [Tiefenthaller, Christian; Bauer, Jan; Lassmann, Hans] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria.; [Karagogeos, Domna] Univ Crete, Sch Med, Inst Mol Biol & Biophys, GR-71110 Iraklion, Greece.; [Linington, Christopher] Univ Glasgow, Div Clin Neurosci, Glasgow G51 4TF, Lanark, Scotland.
Identifiers:ISI:000266209000040 [ID No:1]
ISSN:0027-8424 [ID No:2]
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