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COX5A as a potential biomarker for disease activity and organ damage in lupus

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Abstract

Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease with limited therapeutic targets or clinical outcome predictors. This study aimed to gain more insights into the underlying immunological pathways and prognostic biomarkers of SLE. Integrated analyses of RNA-seq data from 64 SLE and 62 healthy controls, examining 27 immune cell types to explore the key pathways and driver genes in SLE pathogenesis. Single-cell RNA sequencing data from the skin and kidney were used to determine the association of COX5A expression with organ damage. The associations of COX5A with SLE phenotypes were further evaluated in two independent cohorts, and receiver operating characteristic (ROC) curves were constructed to assess the value of COX5A as a biomarker for disease activity and organ damage in SLE. We found that oxidative phosphorylation (OXPHOS) is the most significantly altered metabolic pathway in SLE, especially in effector T cells. Notably, we identified an OXPHOS-related enzyme, COX5A, whose expression was significantly higher in effector T cells than in naïve T cells and showed associations with disease activity, organ damage, and steroid treatment of SLE. Furthermore, ROC curves showed that COX5A is a robust biomarker for disease activity, kidney involvement, and new-onset skin lesions, with the area under the curve (AUC) values of 0.880, 0.801, and 0.805, respectively. Our results identified the OXPHOS signature as a prominent feature in SLE T cells, and COX5A as a potential candidate biomarker for disease activity and organ damage in SLE.

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Data availability

All data generated or analysed during this study are included in SI. 1.

Abbreviations

AUC:

Area under the curve

DEGs:

Differentially expressed genes

GO:

Gene Ontology

GSEA:

Gene Set Enrichment Analysis

GSVA:

Gene Set Variation Analysis

ISG:

Interferon-stimulated genes

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LFSR:

Local false sign rate

logCPM:

Log-transformed count per million

MsigDb:

Molecular Signatures Database

OXPHOS:

Oxidative phosphorylation

PCA:

Principal components analysis

PPI:

Protein–protein interaction

qRT‒PCR:

Quantitative real-time PCR

ROC:

Receiver operating characteristic

SLE:

Systemic Lupus Erythematosus

UMAP:

Uniform manifold approximation and projection

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Acknowledgements

Not applicable.

Funding

This work was supported by the Joint Fund of Medical Sciences of the University of Science and Technology [grant number: YD9110002022].

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Author notes

  1. Minglong Cai and Yi Qin contributed equally to this paper.

Authors and Affiliations

  1. Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China

    Minglong Cai, Yi Qin, An Wan, Huizhi Jin & Zhu Chen

  2. Department of Dermatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China

    Jun Tang

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  1. Minglong Cai
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Contributions

MC, YQ, JT, and ZC contributed to the conception of the work. MC and YQ analyzed the data. MC wrote the first draft and YQ, JT, and ZC made critical revisions to the manuscript. AW and HJn participated in the acquisition of data and laboratory studies and reviewed the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jun Tang or Zhu Chen.

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Competing Interest

The authors have no relevant financial or non-financial interests to disclose.

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Written informed consent was obtained from all individual participants included in the study.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the institutional ethics committee of the First Affiliated Hospital of University of Science and Technology of China.

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Cai, M., Qin, Y., Wan, A. et al. COX5A as a potential biomarker for disease activity and organ damage in lupus. Clin Exp Med 23, 4745–4756 (2023). https://doi.org/10.1007/s10238-023-01215-w

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