Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis
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 pat...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2013
|
| Online Access: | http://hdl.handle.net/1721.1/76598 https://orcid.org/0000-0002-1090-6071 |
| _version_ | 1826193785759989760 |
|---|---|
| author | Ploegh, Hidde Spooner, Eric Ray, Arundhati Amato, Anthony A. Bradshaw, Elizabeth M. Felice, Kevin J. DiCapua, Daniel B. Goldstein, Jonathan M. Lundberg, Ingrid E. Nowak, Richard J. Willis, Simon N. O’Connor, Kevin C. Wu, Qian, 1972- |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ploegh, Hidde Spooner, Eric Ray, Arundhati Amato, Anthony A. Bradshaw, Elizabeth M. Felice, Kevin J. DiCapua, Daniel B. Goldstein, Jonathan M. Lundberg, Ingrid E. Nowak, Richard J. Willis, Simon N. O’Connor, Kevin C. Wu, Qian, 1972- |
| author_sort | Ploegh, Hidde |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:45:22Z |
| format | Article |
| id | mit-1721.1/76598 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:45:22Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/765982022-09-30T16:35:27Z Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis Ploegh, Hidde Spooner, Eric Ray, Arundhati Amato, Anthony A. Bradshaw, Elizabeth M. Felice, Kevin J. DiCapua, Daniel B. Goldstein, Jonathan M. Lundberg, Ingrid E. Nowak, Richard J. Willis, Simon N. O’Connor, Kevin C. Wu, Qian, 1972- Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Ploegh, Hidde Spooner, Eric 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. 2013-01-24T18:29:42Z 2013-01-24T18:29:42Z 2012-10 2012-06 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/76598 Ray, Arundhati et al. “Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis.” Ed. Paolo Fiorina. PLoS ONE 7.10 (2012): e46709. https://orcid.org/0000-0002-1090-6071 en_US http://dx.doi.org/10.1371/journal.pone.0046709 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Ploegh, Hidde Spooner, Eric Ray, Arundhati Amato, Anthony A. Bradshaw, Elizabeth M. Felice, Kevin J. DiCapua, Daniel B. Goldstein, Jonathan M. Lundberg, Ingrid E. Nowak, Richard J. Willis, Simon N. O’Connor, Kevin C. Wu, Qian, 1972- Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title | Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title_full | Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title_fullStr | Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title_full_unstemmed | Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title_short | Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis |
| title_sort | autoantibodies produced at the site of tissue damage provide evidence of humoral autoimmunity in inclusion body myositis |
| url | http://hdl.handle.net/1721.1/76598 https://orcid.org/0000-0002-1090-6071 |
| work_keys_str_mv | AT ploeghhidde autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT spoonereric autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT rayarundhati autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT amatoanthonya autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT bradshawelizabethm autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT felicekevinj autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT dicapuadanielb autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT goldsteinjonathanm autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT lundbergingride autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT nowakrichardj autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT willissimonn autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT oconnorkevinc autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis AT wuqian1972 autoantibodiesproducedatthesiteoftissuedamageprovideevidenceofhumoralautoimmunityininclusionbodymyositis |