Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

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Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis

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dc.contributor.author Ray, Arundhati
dc.contributor.author Amato, Anthony A.
dc.contributor.author Bradshaw, Elizabeth M.
dc.contributor.author Felice, Kevin J.
dc.contributor.author DiCapua, Daniel B.
dc.contributor.author Goldstein, Jonathan M.
dc.contributor.author Lundberg, Ingrid E.
dc.contributor.author Nowak, Richard J.
dc.contributor.author Ploegh, Hidde L.
dc.contributor.author Spooner, Eric
dc.contributor.author Wu, Qian
dc.contributor.author Willis, Simon N.
dc.contributor.author O’Connor, Kevin C.
dc.date.accessioned 2013-04-10T15:04:05Z
dc.date.issued 2012
dc.identifier.citation Ray, Arundhati, Anthony A. Amato, Elizabeth M. Bradshaw, Kevin J. Felice, Daniel B. DiCapua, Jonathan M. Goldstein, Ingrid E. Lundberg, et al. 2012. Autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis. PLoS ONE 7(10): e46709. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:10522859
dc.description.abstract Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0046709 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465259/pdf/ en_US
dash.license LAA
dc.subject Biology en_US
dc.subject Immunology en_US
dc.subject Immunity en_US
dc.subject Humoral Immunity en_US
dc.subject Autoimmunity en_US
dc.subject Immunoglobulins en_US
dc.subject Immunologic Techniques en_US
dc.subject Immunopathology en_US
dc.subject Proteomics en_US
dc.subject Spectrometric Identification of Proteins en_US
dc.subject Medicine en_US
dc.subject Clinical Immunology en_US
dc.subject Autoimmune Diseases en_US
dc.subject Neurology en_US
dc.subject Neuromuscular Diseases en_US
dc.title Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Amato, Anthony A.
dc.date.available 2013-04-10T15:04:05Z

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