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Single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis

ABSTRACT: single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis

PROVIDER: PRJNA1083512 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28215334_1.fastq.gz	Fastqsanger.gz
	SRR28215334_2.fastq.gz	Fastqsanger.gz

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single-cell transcriptomics in patients with anti-citrullinated peptide antibody-positive early rheumatoid arthritis

Project description:Despite known differences in immunologic features between anti-citrullinated peptide antibody (ACPA)-positive (ACPA+) and ACPA-negative (ACPA-) early rheumatoid arthritis (eRA) patients, our understanding is still incomplete. To address this, we performed single-cell RNA sequencing of CD45+ cells from peripheral blood samples of drug-naïve ACPA+ and ACPA- eRA patients and compared distribution and functional characteristics of cell subsets based on ACPA presence.

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Project description:Anti-citrullinated protein antibodies (ACPAs) are one of the hallmarks in rheumatoid arthritis (RA), but the in vivo function remained unclear. To investigate the effects of ACPAs, we expressed monoclonal ACPAs derived from RA patients, and analyzed the functions in mouse models, as well as the reactivity to tissue and peptides/proteins. All ACPAs showed no arthritogenicity and could not induce pain-like behavior in mice whereas one of them (E4) profoundly protected against antibody-induced arthritis. E4 showed a tissue binding pattern restricted to skin epithelial cells, to macrophages and dendritic cells in lymphoid tissue and to cartilage from mouse and human arthritic joints. Proteomic analysis showed that E4 had a distinct binding pattern to macrophage and RA synovial fluid proteins (e.g. alpha-enolase). The protective effect was epitope specific but also dependent on Fc-FCGR2B interaction on macrophages following the immune complex formation, resulting an increased IL-10 production and osteoclastogenesis reduction. The findings suggest that certain ACPAs could be protective in arthritis with therapeutic potentials.

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Arthritis protection conferred by a subset of antibodies to citrullinated proteins in rheumatoid arthritis - human synovium fluids samples

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