Session Information
Session Type: Poster Session C
Session Time: 10:30AM-12:30PM
Background/Purpose: Juvenile idiopathic arthritis (JIA) is a prevalent rheumatic disease in children, comprising seven subtypes. The most common, oligoarticular JIA (oJIA), accounts for 30-60% of cases, often presenting with asymmetrical arthritis and a high risk for uveitis (oJIA-U). The specific immune cells causing synovial inflammation and uveitis remain unclear. While studies on T cells in oJIA have focused on CD4+ T cells, the role of other immune subsets like CD8+ T cells and innate immune cells is increasingly recognized.
Methods: To identify pathogenic immune cells in oJIA, we performed single-cell RNA sequencing (scRNA-Seq, 10x Genomics) and TCR sequencing on 132,824 peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MCs) from three newly diagnosed oJIA patients. We also analyzed PBMCs from four oJIA-U patients and four healthy controls (HCs). Analysis of scRNA-Seq data included differential abundance of cell subtypes, differential gene expression as well as characterization of the and the clonal architecture of alpha-/beta-paired T-cell receptor strands in SF and PB. Additionally, we characterized the plasma proteomic profile from newly diagnosed oJIA, oJIA-U, HCs with a panel 235 proteins related with inflammation (Olink).
Results: Intermediate monocytes, regulatory T cells, activated CD8+ T cells, and NKG2C+ effector memory CD8+ T cells were found in the SF of oJIA patients. These cell populations were also found to be significantly reduced in the PB of oJIA patients, indicating active recruitment to inflamed synovium (P< 0.05). Significant transcriptional differences in activated effector memory CD8+ T cells and NKG2C+ effector memory CD8+ T cells from SF and PB of oJIA patients compared to HCs showed overexpression of key proinflammatory genes like CCL5, GMZA, GZMK and CXCL13 (FDR< 0.05). In oJIA-U patients, circulating dendritic cells types 1 and 4, and mature NK cells were more prevalent compared to oJIA patients without uveitis as well as HCs. These cells in PB from oJIA-U patients had up-regulation of type I and III interferon signaling and MHC class I antigen processing, with CD56+ dim mature NKs overexpressing PRF1, FECR1G, CCL4 (MIP-1β), and B2M. Plasma protein analysis showed increased levels of innate immune proteins like FGF-23, TRAIL, C2, IL-18R1, and IL-6 in oJIA patients compared to HCs (P< 0.05). Severe oJIA-U patients had elevated GZH and MMP-1 plasmatic levels, consistent with innate immune cell involvement.
Conclusion: This study provides the first combined single-cell atlas of oJIA and oJIA-U, providing insights into cellular dynamics and potential cellular drivers of both pediatric rheumatologic diseases. Investigating these populations may improve understanding of underlying mechanisms and help to develop more specific therapeutic strategies.
To cite this abstract in AMA style:
Lopez Corbeto M, Guillen y, Bonafonte I, Palau N, Tortosa R, Moreno Ruzafa E, Julia A, Marsal S. Characterization of Pathogenic Immune Mechanisms in Oligoarticular Juvenile Idiopathic Arthritis Applying Single-cell Transcriptomics and Proteomics [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/characterization-of-pathogenic-immune-mechanisms-in-oligoarticular-juvenile-idiopathic-arthritis-applying-single-cell-transcriptomics-and-proteomics/. Accessed .« Back to ACR Convergence 2024
ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-pathogenic-immune-mechanisms-in-oligoarticular-juvenile-idiopathic-arthritis-applying-single-cell-transcriptomics-and-proteomics/