Shared recognition of citrullinated tenascin-C peptides by T and B cells in rheumatoid arthritis

Area of Science:

• Immunology
• Rheumatology
• Extracellular Matrix Biology

Background:

• Tenascin-C (TNC) is an extracellular matrix protein with pro-inflammatory properties.
• TNC is a recently identified antibody target in rheumatoid arthritis (RA).
• Citrullinated autoantigens are key players in RA pathogenesis.

Purpose of the Study:

• To identify novel citrullinated Tenascin-C (cit-TNC) T cell epitopes in rheumatoid arthritis (RA).
• To investigate the presence and activation status of T cells specific for cit-TNC epitopes in RA patients.
• To explore the role of cit-TNC-specific T cells and antibodies in RA autoimmunity.

Main Methods:

• Systematic epitope discovery process to identify cit-TNC T cell epitopes.
• Analysis of peripheral blood and synovial fluid T cells for cit-TNC epitope specificity and activation markers.
• Detection of cit-TNC-reactive antibodies in serum and synovial fluid.
• Correlation analysis with RA disease markers like anti-CCP antibodies, rheumatoid factor, and HLA shared epitope.

Main Results:

• Five novel cit-TNC T cell epitopes were identified.
• CD4+ T cells specific for these epitopes were elevated and activated in RA patients' peripheral blood.
• Cit-TNC-specific T cells were found in synovial fluid, secreting IFN-γ.
• Two cit-TNC epitopes were recognized by both T cells and antibodies in RA patients.
• Prevalence of cit-TNC-reactive antibodies in RA serum, associated with anti-CCP, HLA shared epitope, rheumatoid factor, and smoking history.

Conclusions:

• Citrullinated Tenascin-C (cit-TNC) is confirmed as an autoantigen targeted by autoreactive CD4+ T cells and autoantibodies in rheumatoid arthritis (RA).
• The presence of T cell and B cell epitopes on cit-TNC suggests a mechanism for amplifying autoimmunity in RA.
• These findings highlight cit-TNC as a potential contributor to RA development and progression.