ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0052

Single Cell RNA-sequencing Analysis Revealed Peripheral Blood and Synovial Alterations of Dendritic Cells in Rheumatoid Arthritis

Yuichi Suwa1, Saeko Yamada1, Toshiyuki Ushijima2, Hideyuki Takahashi2, Tomohisa Okamura1, Yasuo Nagafuchi3 and Keishi Fujio4, 1Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Japan., Bunkyo, Tokyo, Japan, 2Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Japan., Bunkyo-ku, Tokyo, Japan, 3Department of Functional Genomics and Immunological Diseases, Graduate Schoold of Medicine, the University of Tokyo, Tokyo, Japan, 4Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Bunkyo, Tokyo, Japan

Meeting: ACR Convergence 2024

Keywords: Dendritic cells, Disease Activity, rheumatoid arthritis

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Saturday, November 16, 2024

Title: RA – Etiology & Pathogenesis Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Recent single cell analyses have unveiled novel dendritic cell (DC) subpopulations that could potentially be linked to rheumatoid arthritis (RA). This study aimed to elucidate DC dynamics in RA through single cell RNA-sequencing (scRNA-seq) analysis.

Methods: Peripheral blood from 20 RA patients and 4 healthy controls (HC) was sorted for CD45+ CD3/16/19/88/89– HLA-DR+ live cells to construct a scRNA-seq/CITE-seq library of DCs. We assessed the correlation between DC subpopulation proportions and gene expressions with clinical features (Figure 1A). Additionally, we reanalyzed public AMP RA phase 2 synovium scRNA-seq data from RA and osteoarthritis (OA) patients .

Results: In our peripheral blood and synovium scRNA-seq analysis, DCs were classified into plasmacytoid DC (pDC) and four myeloid DC clusters: classical DC1 (DC1), classical DC2 with different CD5 expressions (CD5+ DC2, CD5– DC2), DC3, and precursors of classical DCs (pre-DC) (Figure 1B). In the peripheral blood mixed-effects association testing for single cells, RA patients showed a decrease in DC1 and CD5– DC2 and an increase in pre-DC and pDC compared to HC. Among RA patients, those with high disease activity demonstrated significantly decreased DC1 and DC2 and increased pDC. Conversely, RA synovium displayed a notable increase in cDC1 and CD5– DC2 compared to OA (Figure 1C). Differentially expressed gene (DEG) analysis in RA patients revealed a large number of DEGs in cDC2 clusters in both peripheral blood and RA synovium. CD5– cDC2 exhibited heightened CD83 activation marker expression in both datasets, with elevated SPP1 expression in RA synovium. Gene Set Enrichment Analysis indicated that active RA upregulated type I and II interferon signaling in cDC clusters in both peripheral blood and synovium. Regarding DC cluster interactions with other immune cell clusters, CD5– cDC2 and DC1 abundance significantly correlated positively with peripheral helper T cell (Tph) in RA synovium who had had an inadequate response to TNF inhibitors (Figure 1D). These DC clusters showed enhanced interactions of CCL16-CXCR6, SPP1 signaling, and antigen presentation with Tph in patients with an inadequate response.

Conclusion: The decrease in cDC1 and CD5– cDC2 in RA peripheral blood may correspond to the increase in these mature DCs in the RA synovium (Figure 1E). Targeted scRNA-seq analysis of rare DCs can contribute to understanding RA pathology and offer novel candidate therapeutic targets.

Supporting image 1

Figure 1. Alteration of DC subpopulations in Rheumatoid Arthritis.
(A) Study overview. (B) UMAP of DC clusters in peripheral blood and synovial scRNA-seq data. (C) MASC analysis of DC clusters in peripheral blood (left) and synovial (right) datasets. * < Bonferroni-adjusted p value < 0.05. (D) A heatmap of the correlation coefficients of the proportions of synovial DC clusters and CD4+ T cell clusters in RA patients with an inadequate response to TNF-inhibitors (n = 16). Cross marks indicate Pearson correlation p value > 0.05. (E) Schematic summary of this study. Blue arrows represent changes in peripheral blood, and red arrows indicate changes in the synovium of the DC clusters.
HDA, high disease activity; LDA, low disease activity; PBMC, peripheral blood mononuclear cells; FACS, fluorescence-activated cell sorting; DC, dendritic cell; MASC, mixed-effects association testing for single cells; DEG, differentially expressed gene; GSEA, gene set enrichment analysis.


Disclosures: Y. Suwa: None; S. Yamada: AstraZeneca, 6, Bristol-Myers Squibb(BMS), 6, Pfizer, 6; T. Ushijima: None; H. Takahashi: None; T. Okamura: Chugai Pharmaceutical, 12, TO belonged to the Social Cooperation Program, Department of functional genomics and immunological diseases, supported by this company., Science Japan, 6; Y. Nagafuchi: AbbVie/Abbott, 6, Bristol-Myers Squibb(BMS), 6, Chugai Pharmaceutical, 12, YN belonged to the Social Cooperation Program, Department of functional genomics and immunological diseases, supported by Chugai Pharmaceutical., Novartis, 6; K. Fujio: AbbVie/Abbott, 5, 6, Alexion, 6, Asahi Kasei Pharma, 1, 2, 5, 6, AstraZeneca, 5, 6, Bristol-Myers Squibb(BMS), 5, 6, Chugai Pharmaceutical, 5, 6, Daiichi-Sankyo, 6, Eisai, 5, 6, Eli Lilly, 6, Gilead, 6, GlaxoSmithKlein(GSK), 6, Mitsubishi Tanabe Pharma, 6, Novartis, 6, Pfizer, 6, Taisho Pharmaceutical, 5, 6, Tsumura, 5.

To cite this abstract in AMA style:

Suwa Y, Yamada S, Ushijima T, Takahashi H, Okamura T, Nagafuchi Y, Fujio K. Single Cell RNA-sequencing Analysis Revealed Peripheral Blood and Synovial Alterations of Dendritic Cells in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/single-cell-rna-sequencing-analysis-revealed-peripheral-blood-and-synovial-alterations-of-dendritic-cells-in-rheumatoid-arthritis/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/single-cell-rna-sequencing-analysis-revealed-peripheral-blood-and-synovial-alterations-of-dendritic-cells-in-rheumatoid-arthritis/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology