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Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis.

Abstract

The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN(76-100) (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN(76-100)-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN(1-39) that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

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  • Authors+Show Affiliations

    ,

    Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, Germany.

    , , , , ,

    Source

    MeSH

    Adolescent
    Adult
    Amino Acid Sequence
    Animals
    Autoantibodies
    Butyrophilins
    Cattle
    Cross Reactions
    Epitopes
    Female
    Humans
    Immune Sera
    Male
    Membrane Glycoproteins
    Middle Aged
    Milk Proteins
    Molecular Mimicry
    Molecular Sequence Data
    Multiple Sclerosis
    Myelin Proteins
    Myelin-Associated Glycoprotein
    Myelin-Oligodendrocyte Glycoprotein
    Peptide Fragments
    Protein Structure, Tertiary

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

    Language

    eng

    PubMed ID

    14688379

    Citation

    Guggenmos, Johannes, et al. "Antibody Cross-reactivity Between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis." Journal of Immunology (Baltimore, Md. : 1950), vol. 172, no. 1, 2004, pp. 661-8.
    Guggenmos J, Schubart AS, Ogg S, et al. Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. J Immunol. 2004;172(1):661-8.
    Guggenmos, J., Schubart, A. S., Ogg, S., Andersson, M., Olsson, T., Mather, I. H., & Linington, C. (2004). Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. Journal of Immunology (Baltimore, Md. : 1950), 172(1), pp. 661-8.
    Guggenmos J, et al. Antibody Cross-reactivity Between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis. J Immunol. 2004 Jan 1;172(1):661-8. PubMed PMID: 14688379.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. AU - Guggenmos,Johannes, AU - Schubart,Anna S, AU - Ogg,Sherry, AU - Andersson,Magnus, AU - Olsson,Tomas, AU - Mather,Ian H, AU - Linington,Christopher, PY - 2003/12/23/pubmed PY - 2004/4/3/medline PY - 2003/12/23/entrez SP - 661 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 172 IS - 1 N2 - The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN(76-100) (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG(76-100) in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN(76-100)-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN(1-39) that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/14688379/full_citation L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=14688379 DB - PRIME DP - Unbound Medicine ER -