Scenarios for autoimmunization of T and B cells in myasthenia gravis.
We have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic ep...
| Egile Nagusiak: | , , , , , , , , , , , , , , , |
|---|---|
| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
2003
|
| _version_ | 1826261969426972672 |
|---|---|
| author | Shiono, H Roxanis, I Zhang, W Sims, G Meager, A Jacobson, L Liu, J Matthews, I Wong, Y Bonifati, M Micklem, K Stott, D Todd, J Beeson, D Vincent, A Willcox, N |
| author_facet | Shiono, H Roxanis, I Zhang, W Sims, G Meager, A Jacobson, L Liu, J Matthews, I Wong, Y Bonifati, M Micklem, K Stott, D Todd, J Beeson, D Vincent, A Willcox, N |
| author_sort | Shiono, H |
| collection | OXFORD |
| description | We have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy. |
| first_indexed | 2024-03-06T19:28:56Z |
| format | Journal article |
| id | oxford-uuid:1cc711f2-d27c-44e9-98d9-a5ee2a68c834 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:28:56Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:1cc711f2-d27c-44e9-98d9-a5ee2a68c8342022-03-26T11:07:24ZScenarios for autoimmunization of T and B cells in myasthenia gravis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1cc711f2-d27c-44e9-98d9-a5ee2a68c834EnglishSymplectic Elements at Oxford2003Shiono, HRoxanis, IZhang, WSims, GMeager, AJacobson, LLiu, JMatthews, IWong, YBonifati, MMicklem, KStott, DTodd, JBeeson, DVincent, AWillcox, NWe have studied responses in thymoma patients to interferon-alpha and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy. |
| spellingShingle | Shiono, H Roxanis, I Zhang, W Sims, G Meager, A Jacobson, L Liu, J Matthews, I Wong, Y Bonifati, M Micklem, K Stott, D Todd, J Beeson, D Vincent, A Willcox, N Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title | Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title_full | Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title_fullStr | Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title_full_unstemmed | Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title_short | Scenarios for autoimmunization of T and B cells in myasthenia gravis. |
| title_sort | scenarios for autoimmunization of t and b cells in myasthenia gravis |
| work_keys_str_mv | AT shionoh scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT roxanisi scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT zhangw scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT simsg scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT meagera scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT jacobsonl scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT liuj scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT matthewsi scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT wongy scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT bonifatim scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT micklemk scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT stottd scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT toddj scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT beesond scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT vincenta scenariosforautoimmunizationoftandbcellsinmyastheniagravis AT willcoxn scenariosforautoimmunizationoftandbcellsinmyastheniagravis |