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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1483393

Single-cell RNA Sequencing of Circulating Immune Cells Supports Inhibition of TNFAIP3 and NFKBIA Translation as Psoriatic Arthritis Biomarkers

Provisionally accepted
Ameth N Garrido Ameth N Garrido 1Rohan Machhar Rohan Machhar 1Omar F Cruz-Correa Omar F Cruz-Correa 1Darshini Ganatra Darshini Ganatra 1Sarah Crome Sarah Crome 2,3Joan Wither Joan Wither 1,4Igor Jurisica Igor Jurisica 1,4DAFNA D GLADMAN DAFNA D GLADMAN 1,5,6*
  • 1 Schroeder Arthritis Institute, University Health Network (UHN), Toronto, Ontario, Canada
  • 2 Ajmera Transplant Centre, Toronto General Hospital, Toronto, Ontario, Canada
  • 3 Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 4 University of Toronto, Toronto, Ontario, Canada
  • 5 Krembil Research Institute, University Health Network, Toronto, Canada
  • 6 Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

The final, formatted version of the article will be published soon.

    Objective: To identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).Methods: Peripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, 3 patients with PsC and 2 HC were profiled using scRNA-seq. Differentially expressed genes (DEGs) identified through scRNA-seq were validated on classical monocytes, and CD4 + and CD8 + T cell subsets derived from an independent cohort of patients using the NanoString nCounter® platform. Protein expression was measured in CD4 + and CD8 + T cells by immunoblotting.Results: A total of 18 immune cell population clusters were identified. Across 18 cell clusters, we identified 234 DEGs. NFKBIA and TNFAIP3 were overexpressed in PsA vs HC and PsC patients. Immunoblotting of the proteins encoded in these genes (IκBα and A20, respectively) showed higher levels in PsA CD4 + T cells compared to HC. Conversely, lower levels were observed in PsA CD8 + T cell lysates compared to HC for both proteins.These results suggest that translation of TNFAIP3 and NFKBIA may be inhibited in PsA CD8 + T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types.

    Keywords: psoriatic arthritis, Psoriasis, ScRNA, TNFAIP3, NFKBIA Word Count: 4, 102

    Received: 19 Aug 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Garrido, Machhar, Cruz-Correa, Ganatra, Crome, Wither, Jurisica and GLADMAN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: DAFNA D GLADMAN, Krembil Research Institute, University Health Network, Toronto, Canada

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