Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis.
JCI Insight
; 6(5)2021 03 08.
Article
en En
| MEDLINE
| ID: mdl-33507879
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
/
Linfocitos B
/
Linfocitos T CD4-Positivos
/
Tenascina
/
Epítopos de Linfocito T
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
JCI Insight
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos