Background/Purpose: Rheumatoid arthritis (RA) is a common, highly debilitating systemic inflammatory condition. To date, little is known about which autoantigens are involved in RA and how T cells which recognize self-proteins may become pathogenic in disease.  Fibrinogen is a common target of autoantibodies in RA patients, and a putative T cell autoantigen involved in disease development.  The goal of this study is to identify and characterize fibrinogen-specific CD4⁺T cells.

Methods: Autoantigen-specific T cells were identified directly ex vivousing peptide-MHC tetramers. To identify individuals carrying the HLA-DRB1*0401 (DR4) allele, HLA typing was performed on healthy blood donors and RA patients using sequence-specific primer PCR.  To identify antigen-specific T cells, tetramer staining was performed at room temperature for 1 hour using tetramers loaded with several fibrinogen peptides.  Memory phenotyping was performed using antibodies against CD45RO and CCR7.  Tetramer tagged cells were magnetically enriched and analyzed by flow cytometry.  Single cell TCR amplification and sequencing was performed to trace T cell clonality. 

Results: We identified several populations of T cells recognizing citrullinated and uncitrullinated fibrinogen peptides.  The frequency of fibrinogen-specific T cells in RA patients ranges between 3 to 19 per million CD4⁺T cells.  Many of these lymphocytes express the memory marker CD45RO, particularly among cells that recognize citrullinated forms of the fibrinogen peptides. Examination of the same antigen-specificities in healthy people demonstrated that the frequency and memory characteristics of these cells appear similar in individuals without disease. Moreover, we also found in some healthy people the presence of clonally expanded T cells that recognize citrullinated fibrinogen. 

Conclusion: T cells that recognize citrullinated fibrinogen can be detected in the peripheral blood of RA patients and healthy individuals.  These fibrinogen-specific populations contain large numbers of antigen-experienced T cells with some showing evidence of clonal expansion.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-and-characterization-of-fibrinogen-specific-t-cells-in-patients-with-rheumatoid-arthritis/