Synovial gene signatures associated with the development of rheumatoid arthritis in at risk individuals: A prospective study.

Autor: de Jong TA; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, Netherlands., de Hair MJH; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands., van de Sande MGH; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, Netherlands., Semmelink JF; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, Netherlands., Choi IY; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, Netherlands., Gerlag DM; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; UCB Pharma, Slough SL1 3XE, UK., Tak PP; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Candel Therapeutics, Needham, MA, USA; Internal Medicine, Cambridge University, Cambridge, CB2 1TN, UK., van Baarsen LGM; Amsterdam UMC, University of Amsterdam, Department of Rheumatology & Clinical Immunology and Department of Experimental Immunology, Amsterdam Infection & Immunity Institute, Amsterdam, Netherlands; Amsterdam Rheumatology & Immunology Center (ARC), Academic Medical Center, Amsterdam, Netherlands. Electronic address: e.g.vanbaarsen@amsterdamumc.nl.
Jazyk: angličtina
Zdroj: Journal of autoimmunity [J Autoimmun] 2022 Dec; Vol. 133, pp. 102923. Date of Electronic Publication: 2022 Oct 06.
DOI: 10.1016/j.jaut.2022.102923
Abstrakt: Objective: To identify molecular changes in synovium before arthritis development in individuals at risk of developing rheumatoid arthritis (RA).
Materials and Methods: We included 67 IgM rheumatoid factor and/or anti-citrullinated protein antibody positive individuals with arthralgia but without arthritis. Synovial biopsies were collected after which individuals were prospectively followed for at least 2 years during which 17 developed arthritis. An exploratory genome-wide transcriptional profiling study was performed in 13 preselected individuals to identify transcripts associated with arthritis development (n = 6). Findings were validated using quantitative real-time PCR and immunohistochemistry in the total cohort.
Results: Microarray-based survival analyses identified 5588 transcripts whose expression levels in synovium were significantly associated with arthritis development. Pathway analysis revealed that synovial tissue of at risk individuals who later developed arthritis display higher expression of genes involved in adaptive immune response-related pathways compared to at risk individuals who did not develop arthritis. Lower expression was observed for genes involved in extracellular matrix receptor interaction, Wnt-mediated signal transduction and lipid metabolism. Two-way hierarchical clustering analyses of a 27-gene signature separated the total at risk cohort into two groups, where pre-RA individuals preferred to cluster together. Immunohistochemistry studies revealed more podoplanin positive cells and lower lipid droplet staining in synovial tissue from pre-RA individuals.
Conclusion: Synovial alterations in adaptive immune response and lipid metabolism are associated with future development of arthritis. Since this data show synovial changes without overt cellular infiltration, these may be attributed to preclinical changes in resident synovial tissue cells such as fibroblasts, macrophages and tissue resident T cells.
Competing Interests: Declaration of competing interest The authors have no competing interests to disclose. PPT is CEO at Candel Therapeutics. MdH is currently an employee of Novartis Pharma NL, and DMG is currently an employee of UCB Pharma. These companies had no involvement in this research.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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