Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs.

Autor: Hedman ÅK; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Department of Inflammation and Immunology, Pfizer, 1 Portland Street, Cambridge, MA, 02139, USA., Winter E; CytoReason, Tel-Aviv, Israel., Yoosuf N; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.; Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden., Benita Y; CytoReason, Tel-Aviv, Israel., Berg L; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Brynedal B; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Folkersen L; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden., Klareskog L; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Maciejewski M; Department of Inflammation and Immunology, Pfizer, 1 Portland Street, Cambridge, MA, 02139, USA., Sirota-Madi A; CytoReason, Tel-Aviv, Israel., Spector Y; CytoReason, Tel-Aviv, Israel., Ziemek D; Department of Inflammation and Immunology, Pfizer, Berlin, Germany., Padyukov L; Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.; Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden., Shen-Orr SS; CytoReason, Tel-Aviv, Israel.; Technion-Israel Institute of Technology, Haifa, Israel., Jelinsky SA; Department of Inflammation and Immunology, Pfizer, 1 Portland Street, Cambridge, MA, 02139, USA. Scott.Jelinsky@Pfizer.com.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Jun 21; Vol. 13 (1), pp. 10058. Date of Electronic Publication: 2023 Jun 21.
DOI: 10.1038/s41598-023-36999-0
Abstrakt: Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation and is mediated by multiple immune cell types. In this work, we aimed to determine the relevance of changes in cell proportions in peripheral blood mononuclear cells (PBMCs) during the development of disease and following treatment. Samples from healthy blood donors, newly diagnosed RA patients, and established RA patients that had an inadequate response to MTX and were about to start tumor necrosis factor inhibitors (TNFi) treatment were collected before and after 3 months of treatment. We used in parallel a computational deconvolution approach based on RNA expression and flow cytometry to determine the relative cell-type frequencies. Cell-type frequencies from deconvolution of gene expression indicate that monocytes (both classical and non-classical) and CD4 + cells (T h 1 and T h 2) were increased in RA patients compared to controls, while NK cells and B cells (naïve and mature) were significantly decreased in RA patients. Treatment with MTX caused a decrease in B cells (memory and plasma cell), and a decrease in CD4 T h cells (T h 1 and T h 17), while treatment with TNFi resulted in a significant increase in the population of B cells. Characterization of the RNA expression patterns found that most of the differentially expressed genes in RA subjects after treatment can be explained by changes in cell frequencies (98% and 74% respectively for MTX and TNFi).
(© 2023. The Author(s).)
Databáze: MEDLINE
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