Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease characterized by peripheral polyarthritis. The importance of CD4+ T cell in the pathophysiology of RA is well-known and it has been reported that the diversity of T cell receptor (TCR) of CD4+ T cells is decreased in rheumatoid arthritis. However, the relationship between the decrease of TCR repertoire diversity of CD4+ T cells and RA pathophysiology remains unclear. To investigate the significance of this phenomenon in RA pathophysiology, we analyzed TCR repertoire and its association with disease activity and other parameters related to RA.
Methods: Peripheral blood CD4+ memory (CD3+CD4+CD45RA-) and naïve (CD3+CD4+CD45RA+) T cells from 18 RA patients and 21 age and sex-matched healthy donors were obtained. All RA patients satisfied the 2010 ACR/EULAR classification criteria for RA. cDNAs of TCR-beta were synthesized and amplified by 5’-race method. Sequencing was performed by Miseq. Concentrations of serum cytokines were assessed with Multiplex ELAISA. Renyi entropy was used to comprehensively assess TCR repertoire diversity, and correlation with disease activity, concentrations of serum cytokines, the number of shared epitope alleles and other clinical parameters was examined.
Results: TCR repertoire diversity of both memory and naïve CD4+ T cells was significantly reduced in RA patients with high disease activity compared to healthy donors. It is generally thought that the reduction of TCR diversity of CD4+ T cells reflects the existence of antigen specific immune responses in RA, and this immune response may be associated with antigens presented on HLA class II. Our results showed a positive correlation between the dosage of shared epitope and reduction of TCR repertoire diversity in CD4+ T cells. Also, there was a negative correlation between TCR repertoire diversity of CD4+ T cells and disease activity indices, such as Disease Activity Score (DAS) 28-CRP, DAS28-ESR, and Clinical Disease Activity Index (CDAI). On the other hand, concentrations of serum cytokines, including pro-inflammatory cytokines, did not show significant correlation with TCR repertoire diversity of CD4+ T cells. These phenomenon were found not only in CD4+ memory T cells but also in CD4+ naïve T cells.
Conclusion: Our results suggest that antigen specific immune responses of CD4+ T cells to self-antigens presented on HLA class II with shared epitope may contribute to the pathophysiology of rheumatoid arthritis in a different manner from inflammatory cytokines. These antigen specific responses, not only in CD4+ memory T cells subset, but also in CD4+ naïve T cells subset, may be related to RA pathophysiology and may suggest the importance of homeostatic expansion in RA.
To cite this abstract in AMA style:Sakurai K, Shoda H, Ishigaki K, Tsuchida Y, Nagafuchi Y, Sumitomo S, Suzuki A, Fujio K, Yamamoto K. Analysis of T Cell Repertoire Diversity of CD4+ Memory and NaïVe T Cells By Next Generation Sequencing and Its Association with Rheumatoid Arthritis Disease Parameters [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/analysis-of-t-cell-repertoire-diversity-of-cd4-memory-and-naive-t-cells-by-next-generation-sequencing-and-its-association-with-rheumatoid-arthritis-disease-parameters/. Accessed November 25, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/analysis-of-t-cell-repertoire-diversity-of-cd4-memory-and-naive-t-cells-by-next-generation-sequencing-and-its-association-with-rheumatoid-arthritis-disease-parameters/