AB1128 SINGLE-CELL RNA SEQUENCING REVEALS CROSS-DISEASE CHARACTERIZATIONS OF TREATMENT-NAÏVE AUTOIMMUNE DISEASES AND DISTINCT INTERFERON SIGNATURES IN SYSTEMIC LUPUS ERYTHEMATOSUS

• Published in: Annals of the rheumatic diseases Vol. 83; no. Suppl 1; p. 1896
• Main Authors: Zhang, Z., Fan, Y., Geng, Y., Ye, X., Zhao, J., Huang, H., Zhang, J.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2024; Elsevier B.V; Elsevier Limited
• Subjects: Adaptive immunity; Arthritis; Autoimmune diseases; CD14 antigen; CD16 antigen; CD4 antigen; Cytokines and Chemokines; Effector cells; Factor analysis; Immunological memory; Inflammatory diseases; Innate immunity; Interferon; Interferon regulatory factor 7; Leukocytes (mononuclear); Lupus; Lymphocytes B; Memory cells; Monocytes; Peripheral blood mononuclear cells; Psoriatic arthritis; Rheumatic diseases; Rheumatoid arthritis; Scientific Abstracts; Stat1 protein; Systemic lupus erythematosus; Transcriptomes; Innate immunity; Adaptive immunity; Cytokines and Chemokines
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2024-eular.4656

Background:Autoimmune diseases encompass a wide array of conditions characterized primarily by immune dysregulation, comprising hundreds of distinct diseases. However, the pathogenic mechanisms of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and inflammatory arthritis diseases like rheumatoid arthritis (RA) and spondyloarthritis may exhibit substantial differences [1].Objectives:To offer additional insights and clues into the pathogenesis of autoimmune diseases by using single-cell sequencing technology.Methods:Peripheral blood mononuclear cells (PBMC) from 14 treatment-naïve patients with autoimmune diseases, including 6 cases of RA, 4 cases of psoriatic arthritis (PsA), and 4 cases of SLE, along with 5 healthy control subjects were prospectively collected. Single-cell RNA sequencing (scRNA-seq) were performed using the 10x Genomics Single Cell technique.Results:From a total of ~130,000 cells, we identified 10 major clusters comprising 30 subtypes of cells. Comparing with the healthy control group, CD4+ effector memory cells showed a significant increase in RA and PsA patients, but no significant change in SLE. Conversely, CD14+CD16+ monocytes only showed a significant increase in SLE. Unswitched memory B cells and γδT cells in patients with autoimmune diseases exhibited a decrease in proportion, with the most pronounced decrease in SLE, followed by RA. Notably, GSEA analysis demonstrated a significant enhancement in the inflammatory response gene scores in all three patient groups, with the most significant increase in SLE. Furthermore, the type I interferon response genes and, especially Interferon Alpha And Beta Receptor Subunit 1/2 (IFNAR1/2) were significantly increased only in SLE, primarily expressed in the monocyte, DC, NK, and plasma cell subgroups. Meanwhile, type II interferon response genes showed a significant increase in SLE, a mild increase in RA, and no increase in PsA. Transcription factor analysis revealed the critical role of IRF7-STAT1 in regulating the type I interferon response in SLE.Conclusion:Different autoimmune diseases may present distinct immune cell landscape at single cell levels. SLE exhibits a more unique interferon signatures, regulated by IRF7-STAT1. The notable elevation of IFNAR1/2 exclusively in SLE patients implies that the potential efficacy of type I interferon receptor antagonists may be limited in SLE, but possibly not in inflammatory arthritis.REFERENCES:[1] Zeng L, Yang K, Zhang T, et al. Research progress of single-cell transcriptome sequencing in autoimmune diseases and autoinflammatory disease: A review. J Autoimmun. 2022;133:102919. doi:10.1016/j.jaut.2022.102919Acknowledgements:NIL.Disclosure of Interests:None declared.