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  Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals

Derfuss, T., Parikh, K., Velhin, S., Braun, M., Mathey, E., Krumbholz, M., et al. (2009). Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proceedings of the National Academy of Sciences of the United States of America, 106(20), 8302-8307.

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 Creators:
Derfuss, T.1, Author              
Parikh, K.2, Author
Velhin, S.1, Author              
Braun, M.3, Author              
Mathey, E.2, Author
Krumbholz, M.1, Author              
Kümpfel, T.1, Author              
Moldenhauer, A.2, Author
Rader, C.2, Author
Sonderegger, P.2, Author
Pöllmann, W.2, Author
Tiefenthaller, C.2, Author
Bauer, J.2, Author
Lassmann, H.2, Author
Wekerle, H.1, Author              
Karagogeos, D.2, Author
Hohlfeld, R.1, Author              
Linington, C.1, Author              
Meinl, E.1, Author              
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2[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., ou_persistent22              
3Department: Systems and Computational Neurobiology / Borst, MPI of Neurobiology, Max Planck Society, ou_1113548              

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Free keywords: cortical pathology; experimental autoimmune encephalitis; Th1/Th17 T cells; node of Ranvier; myelin glycoproteins
 Abstract: 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.

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Language(s): eng - English
 Dates: 2009-05-19
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 432448
ISI: 000266209000040
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Alternative Title : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 106 (20) Sequence Number: - Start / End Page: 8302 - 8307 Identifier: ISSN: 0027-8424