The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls

C. G. Haase, J. Guggenmos, U. Brehm, M. Andersson, T. Olsson, M. Reindl, J. M. Schneidewind, U. K. Zettl, F. Heidenreich, K. Berger, H. Wekerle, R. Hohlfeld, Christopher Linington

    Research output: Contribution to journalArticle

    95 Citations (Scopus)

    Abstract

    Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(lgd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(lgd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FAGS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients. (C) 2001 Elsevier Science B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)220-225
    Number of pages5
    JournalJournal of Neuroimmunology
    Volume114
    Issue number1-2
    DOIs
    Publication statusPublished - Mar 2001

    Keywords

    • multiple sclerosis
    • autoimmunity
    • myelin oligodendrocyte glycoprotein (MOG)
    • B cell response
    • autoantibody
    • epitope specificity
    • EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
    • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
    • B-CELL
    • BASIC-PROTEIN
    • T-CELL
    • DEMYELINATION
    • ANTIBODY
    • LESIONS
    • RATS
    • MOG

    Cite this

    The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls. / Haase, C. G.; Guggenmos, J.; Brehm, U.; Andersson, M.; Olsson, T.; Reindl, M.; Schneidewind, J. M.; Zettl, U. K.; Heidenreich, F.; Berger, K.; Wekerle, H.; Hohlfeld, R.; Linington, Christopher.

    In: Journal of Neuroimmunology, Vol. 114, No. 1-2, 03.2001, p. 220-225.

    Research output: Contribution to journalArticle

    Haase, CG, Guggenmos, J, Brehm, U, Andersson, M, Olsson, T, Reindl, M, Schneidewind, JM, Zettl, UK, Heidenreich, F, Berger, K, Wekerle, H, Hohlfeld, R & Linington, C 2001, 'The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls', Journal of Neuroimmunology, vol. 114, no. 1-2, pp. 220-225. https://doi.org/10.1016/S0165-5728(00)00462-8
    Haase, C. G. ; Guggenmos, J. ; Brehm, U. ; Andersson, M. ; Olsson, T. ; Reindl, M. ; Schneidewind, J. M. ; Zettl, U. K. ; Heidenreich, F. ; Berger, K. ; Wekerle, H. ; Hohlfeld, R. ; Linington, Christopher. / The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls. In: Journal of Neuroimmunology. 2001 ; Vol. 114, No. 1-2. pp. 220-225.
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    T1 - The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls

    AU - Haase, C. G.

    AU - Guggenmos, J.

    AU - Brehm, U.

    AU - Andersson, M.

    AU - Olsson, T.

    AU - Reindl, M.

    AU - Schneidewind, J. M.

    AU - Zettl, U. K.

    AU - Heidenreich, F.

    AU - Berger, K.

    AU - Wekerle, H.

    AU - Hohlfeld, R.

    AU - Linington, Christopher

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    N2 - Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(lgd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(lgd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FAGS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients. (C) 2001 Elsevier Science B.V. All rights reserved.

    AB - Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(lgd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(lgd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FAGS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients. (C) 2001 Elsevier Science B.V. All rights reserved.

    KW - multiple sclerosis

    KW - autoimmunity

    KW - myelin oligodendrocyte glycoprotein (MOG)

    KW - B cell response

    KW - autoantibody

    KW - epitope specificity

    KW - EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

    KW - EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS

    KW - B-CELL

    KW - BASIC-PROTEIN

    KW - T-CELL

    KW - DEMYELINATION

    KW - ANTIBODY

    KW - LESIONS

    KW - RATS

    KW - MOG

    U2 - 10.1016/S0165-5728(00)00462-8

    DO - 10.1016/S0165-5728(00)00462-8

    M3 - Article

    VL - 114

    SP - 220

    EP - 225

    JO - Journal of Neuroimmunology

    JF - Journal of Neuroimmunology

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    ER -