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Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.

ABSTRACT: Rheumatic diseases are a group of highly heterogeneous autoimmune and inflammatory disorders involving multiple systems. Dysfunction of immune and non-immune cells participates in the complex pathogenesis of rheumatic diseases. Therefore, studies on the abnormal activation of cell subtypes provided a specific basis for understanding the pathogenesis of rheumatic diseases, which promoted the accuracy of disease diagnosis and the effectiveness of various treatments. However, there was still a far way to achieve individualized precision medicine as the result of heterogeneity among cell subtypes. To obtain the biological information of cell subtypes, single-cell sequencing, a cutting-edge technology, is used for analyzing their genomes, transcriptomes, epigenetics, and proteomics. Novel results identified multiple cell subtypes in tissues of patients with rheumatic diseases by single-cell sequencing. Consequently, we provide an overview of recent applications of single-cell sequencing in rheumatic disease and cross-tissue to understand the cell subtypes and functions.

SUBMITTER: Ding L

PROVIDER: S-EPMC9662270 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.

Ding Liqing L Li Xiaojing X Zhu Honglin H Luo Hui H

Aging and disease 20221201 6

Rheumatic diseases are a group of highly heterogeneous autoimmune and inflammatory disorders involving multiple systems. Dysfunction of immune and non-immune cells participates in the complex pathogenesis of rheumatic diseases. Therefore, studies on the abnormal activation of cell subtypes provided a specific basis for understanding the pathogenesis of rheumatic diseases, which promoted the accuracy of disease diagnosis and the effectiveness of various treatments. However, there was still a far ...[more]

PMID: 36465169

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Project description:ObjectivesTo investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq).MethodsFrom September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis.ResultsThe anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (β: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group.ConclusionsmRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

Dataset Information

Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.

Publications

Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.

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