Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase

HADJIVASSILIOU, M., AESCHLIMANN, P., STRIGUN, A., SANDERS, D. S., WOODROOFE, N. and AESCHLIMANN, D. (2008). Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Annals of neurology, 64 (3), 332-343.

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Link to published version:: https://doi.org/10.1002/ana.21450
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    Abstract

    Objective: Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.

    Methods: Using recombinant human transglutaminases, we developed enzyme-linked immunosorbent assays and inhibition assays to analyze serum samples of patients with gluten-sensitive gastrointestinal and neurological disorders, and various control groups including unrelated inherited or immune conditions for the presence and specificity of autoantibodies.

    Results: Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6.

    Interpretation: Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.

    Item Type: Article
    Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomolecular Sciences Research Centre
    Identification Number: https://doi.org/10.1002/ana.21450
    Page Range: 332-343
    Depositing User: Users 4 not found.
    Date Deposited: 04 Jun 2010 12:59
    Last Modified: 13 Jun 2017 12:47
    URI: http://shura.shu.ac.uk/id/eprint/2116

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