ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1919

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

Keiichi Sakurai1, Hirofumi Shoda1, Kazuyoshi Ishigaki2, Yumi Tsuchida1, Yasuo Nagafuchi1, Shuji Sumitomo1, Akari Suzuki2, Keishi Fujio1 and Kazuhiko Yamamoto1, 1Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan, 2Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , ,

Session Information

Date: Monday, November 14, 2016

Title: T Cell Biology and Targets in Autoimmune Disease - Poster Session I

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.

Disclosure: K. Sakurai, None; H. Shoda, None; K. Ishigaki, Takeda, 2; Y. Tsuchida, None; Y. Nagafuchi, None; S. Sumitomo, None; A. Suzuki, Takeda, 2; K. Fujio, Bristol-Myers Squibb, 2,Chugai, 2,Takeda, 2,Daiichi-Sankyo, 7,MitsubishiTanabe, 7,Pfizer Inc, 7,Santen, 7,Eisai, 7,Taisho Toyama, 7,UCB., 7,Janssen Pharmaceutica Product, L.P., 7; K. Yamamoto, Bristol-Myers Squibb, 2,Takeda, 2,Chugai, 2,AbbVie, 7,Astellas, 7,Daiichi-Sankyo, 7,MitsubishiTanabe, 7,Pfizer Inc, 7,Sanofi, 7,Santen, 7,Teijin, 7,Boehringer Ingelheim, 7,Eisai, 7,Ono, 7,Taisho Toyama, 7,UCB., 7,ImmunoFuture, 7,Asahi Kasei, 7,Janssen Pharmaceutica Product, L.P., 7.

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 .

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