Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis
Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+...
| Main Authors: | , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2021
|
| _version_ | 1826266806825779200 |
|---|---|
| author | Song, J Schwenzer, A Midwood, KIM |
| author_facet | Song, J Schwenzer, A Midwood, KIM |
| author_sort | Song, J |
| collection | OXFORD |
| description | Tenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC–specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC–reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC–reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA. |
| first_indexed | 2024-03-06T20:44:34Z |
| format | Journal article |
| id | oxford-uuid:356f1c9d-b9e2-4aef-8087-f58631739ad6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:44:34Z |
| publishDate | 2021 |
| publisher | American Society for Clinical Investigation |
| record_format | dspace |
| spelling | oxford-uuid:356f1c9d-b9e2-4aef-8087-f58631739ad62022-03-26T13:31:55ZShared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:356f1c9d-b9e2-4aef-8087-f58631739ad6EnglishSymplectic ElementsAmerican Society for Clinical Investigation2021Song, JSchwenzer, AMidwood, KIMTenascin-C (TNC), an extracellular matrix protein that has proinflammatory properties, is a recently described antibody target in rheumatoid arthritis (RA). In this study, we utilized a systematic discovery process and identified 5 potentially novel citrullinated TNC (cit-TNC) T cell epitopes. CD4+ T cells specific for these epitopes were elevated in the peripheral blood of subjects with RA and showed signs of activation. Cit-TNC–specific T cells were also present among synovial fluid T cells and secreted IFN-γ. Two of these cit-TNC T cell epitopes were also recognized by antibodies within the serum and synovial fluid of individuals with RA. Detectable serum levels of cit-TNC–reactive antibodies were prevalent among subjects with RA and positively associated with cyclic citrullinated peptide (CCP) reactivity and the HLA shared epitope. Furthermore, cit-TNC–reactive antibodies were correlated with rheumatoid factor and elevated in subjects with a history of smoking. This work confirms cit-TNC as an autoantigen that is targeted by autoreactive CD4+ T cells and autoantibodies in patients with RA. Furthermore, our findings raise the possibility that coinciding epitopes recognized by both CD4+ T cells and B cells have the potential to amplify autoimmunity and promote the development and progression of RA. |
| spellingShingle | Song, J Schwenzer, A Midwood, KIM Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title | Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title_full | Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title_fullStr | Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title_full_unstemmed | Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title_short | Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis |
| title_sort | shared recognition of citrullinated tenascin c peptides by t and b cells in rheumatoid arthritis |
| work_keys_str_mv | AT songj sharedrecognitionofcitrullinatedtenascincpeptidesbytandbcellsinrheumatoidarthritis AT schwenzera sharedrecognitionofcitrullinatedtenascincpeptidesbytandbcellsinrheumatoidarthritis AT midwoodkim sharedrecognitionofcitrullinatedtenascincpeptidesbytandbcellsinrheumatoidarthritis |