Resource and Technical AdvanceIn-Press PreviewImmunology
Open Access | 10.1172/jci.insight.178499
1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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1Bakar Computational Health Sciences Institute, UCSF, San Francisco, United States of America
2Division of Rheumatology, Department of Medicine, UCSF, San Francisco, United States of America
3Department of Medicine, Oregon Health & Science University, Portland, United States of America
4Human Genetics, UCSF, San Francisco, United States of America
5Department of Rheumatology, Research Center Saint Antoine, APHP Saint Antoine Hospital and Sorbonne Université, Paris, France
6Immunology Immunopathology Immunotherapy, Pitie Salpetriere Hospital UMRS 959, Sorbonne Université, Paris, France
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Published July 2, 2024 - More info
Rheumatoid arthritis (RA) management lean toward achieving remission or low-disease activity. In this study, we conducted single-cell RNA sequencing (scRNAseq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals (18 RA patients and 18 matched controls, accounting for age, sex, race, and ethnicity), to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity. Our analysis revealed 18 distinct PBMC subsets, including an IFITM3 overexpressing Interferon-activated (IFN-activated) monocyte subset. We observed an increase in CD4+ T effector memory cells in patients with moderate to high disease activity (DAS28-CRP ≥ 3.2), and a decrease in non-classical monocytes in patients with low disease activity or remission (DAS28-CRP < 3.2). Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA and matched controls, with a downregulation of pro-inflammatory genes in the gamma-delta T cells subset, alteration of genes associated with RA predisposition in the IFN-activated subset, and non-classical monocytes. Additionally, we identified a gene signature associated with moderate-high disease activity, characterized by upregulation of pro-inflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, TNFSF13B. Notably, cell-cell communication analysis revealed an upregulation of signaling pathways, including VISTA, in both moderate-high and remission-low disease activity contexts. Our findings provide valuable insights into the systemic cellular and molecular mechanisms underlying RA disease activity.