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Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis

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Abstract

Autoimmune hepatitis (AIH) is an immune disorder characterized by hypergammaglobulinemia, autoantibodies, and chronic active hepatitis on liver histology. However, immune cell population characteristics in AIH patients remain poorly understood. This study was designed to analyze peripheral blood mononuclear cell (PBMC) characteristics in AIH through single-cell RNA sequencing (scRNA-seq) and explore potential AIH-related molecular mechanisms. We generated 3690 and 3511 single-cell transcriptomes of PBMCs pooled from 4 healthy controls (HCs) and 4 AIH patients, respectively, by scRNA-seq. These pooled PBMC transcriptomes were used for cell cluster identification and differentially expressed gene (DEG) identification. GO functional enrichment analysis was performed on the DEGs to determine the most active AIH immune cell biological functions. Although the PCA-based uniform manifold approximation and projection (UMAP) algorithm was used to cluster cells with similar expression patterns in the two samples, 87 up- and 12 downregulated DEGs were retained in monocytes and 101 up- and 15 downregulated DEGs were retained in NK cells from AIH PBMCs. Moreover, enriched GO terms in the PBMC-derived monocyte and NK cell clusters were related mainly to antigen processing and presentation, IFN-γ-mediated signaling, and neutrophil degranulation and activation. These potential molecular mechanisms may be important targets for AIH treatment.

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Acknowledgements

The authors thank Chikako Saito and Rie Hikichi for their technical assistance.

Funding

This work was supported by AbbVie Inc. grant funding (No. 1676, No. 2546).

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Authors and Affiliations

  1. Department of Gastroenterology, Fukushima Medical University, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan

    Kazumichi Abe, Naoto Abe, Tatsuro Sugaya, Yosuke Takahata, Masashi Fujita, Manabu Hayashi, Atsushi Takahashi & Hiromasa Ohira

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  1. Kazumichi Abe
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  2. Naoto Abe
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  3. Tatsuro Sugaya
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  4. Yosuke Takahata
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  7. Atsushi Takahashi
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  8. Hiromasa Ohira
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Contributions

Conceived and designed the experiments: KA and HO. Performed the experiments: KA. Analyzed the data: KA. Contributed materials: KA, NA, TS, YT, AT, MF, and MH. Wrote the paper: KA and HO.

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Correspondence to Kazumichi Abe.

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Ethics statement

All patients and HCs agreed to blood testing, and written informed consent was obtained. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved for use with the informed consent of participants by the ethics committee of Fukushima Medical University School of Medicine (IRB #2020-200).

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Abe, K., Abe, N., Sugaya, T. et al. Characteristics of peripheral blood mononuclear cells and potential related molecular mechanisms in patients with autoimmune hepatitis: a single-cell RNA sequencing analysis. Med Mol Morphol (2024). https://doi.org/10.1007/s00795-024-00380-5

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