Cargando…
Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis
OBJECTIVES: Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups. METHODS: RNASeq was performed on 74 samples, with disease activity data c...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646909/ https://www.ncbi.nlm.nih.gov/pubmed/37507201 http://dx.doi.org/10.1136/ard-2023-224068 |
_version_ | 1785147474174803968 |
---|---|
author | Triaille, Clément Tilman, Gaëlle Sokolova, Tatiana Loriot, Axelle Marchandise, Joelle De Montjoye, Stéphanie Nzeusseu-Toukap, Adrien Méric de Bellefon, Laurent Bouzin, Caroline Galant, Christine Durez, Patrick Lauwerys, Bernard R Limaye, Nisha |
author_facet | Triaille, Clément Tilman, Gaëlle Sokolova, Tatiana Loriot, Axelle Marchandise, Joelle De Montjoye, Stéphanie Nzeusseu-Toukap, Adrien Méric de Bellefon, Laurent Bouzin, Caroline Galant, Christine Durez, Patrick Lauwerys, Bernard R Limaye, Nisha |
author_sort | Triaille, Clément |
collection | PubMed |
description | OBJECTIVES: Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups. METHODS: RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets. Histological assessment and multiplex immunofluorescence (for CD45, CD68, CD206) were performed on paraffin sections. RESULTS: PCA on expression of the (n=894) most variable genes across this series did not divide samples into distinct groups, instead yielding a continuum correlated with baseline disease activity. Two patient clusters (PtC1, n=52; PtC2, n=22) were defined based on expression of these genes. PtC1, with significantly higher disease activity and probability of response to methotrexate therapy, showed upregulation of immune system genes; PtC2 showed upregulation of lipid metabolism genes, described to characterise tissue resident or M2-like macrophages. In keeping with these data, M2-like:M1-like macrophage ratios were inversely correlated with disease activity scores and were associated with lower synovial immune infiltration and the presence of thinner, M2-like macrophage-rich synovial lining layers. CONCLUSION: In this large series of early, untreated RA, we show that the synovial transcriptome closely mirrors clinical disease activity and correlates with synovial inflammation. Intriguingly, lower inflammation and disease activity are associated with higher ratios of M2:M1 macrophages, particularly striking in the synovial lining layer. This may point to a protective role for tissue resident macrophages in RA. |
format | Online Article Text |
id | pubmed-10646909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-106469092023-11-15 Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis Triaille, Clément Tilman, Gaëlle Sokolova, Tatiana Loriot, Axelle Marchandise, Joelle De Montjoye, Stéphanie Nzeusseu-Toukap, Adrien Méric de Bellefon, Laurent Bouzin, Caroline Galant, Christine Durez, Patrick Lauwerys, Bernard R Limaye, Nisha Ann Rheum Dis Early Arthritis OBJECTIVES: Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups. METHODS: RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets. Histological assessment and multiplex immunofluorescence (for CD45, CD68, CD206) were performed on paraffin sections. RESULTS: PCA on expression of the (n=894) most variable genes across this series did not divide samples into distinct groups, instead yielding a continuum correlated with baseline disease activity. Two patient clusters (PtC1, n=52; PtC2, n=22) were defined based on expression of these genes. PtC1, with significantly higher disease activity and probability of response to methotrexate therapy, showed upregulation of immune system genes; PtC2 showed upregulation of lipid metabolism genes, described to characterise tissue resident or M2-like macrophages. In keeping with these data, M2-like:M1-like macrophage ratios were inversely correlated with disease activity scores and were associated with lower synovial immune infiltration and the presence of thinner, M2-like macrophage-rich synovial lining layers. CONCLUSION: In this large series of early, untreated RA, we show that the synovial transcriptome closely mirrors clinical disease activity and correlates with synovial inflammation. Intriguingly, lower inflammation and disease activity are associated with higher ratios of M2:M1 macrophages, particularly striking in the synovial lining layer. This may point to a protective role for tissue resident macrophages in RA. BMJ Publishing Group 2023-12 2023-07-28 /pmc/articles/PMC10646909/ /pubmed/37507201 http://dx.doi.org/10.1136/ard-2023-224068 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Early Arthritis Triaille, Clément Tilman, Gaëlle Sokolova, Tatiana Loriot, Axelle Marchandise, Joelle De Montjoye, Stéphanie Nzeusseu-Toukap, Adrien Méric de Bellefon, Laurent Bouzin, Caroline Galant, Christine Durez, Patrick Lauwerys, Bernard R Limaye, Nisha Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title | Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title_full | Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title_fullStr | Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title_full_unstemmed | Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title_short | Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
title_sort | disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis |
topic | Early Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10646909/ https://www.ncbi.nlm.nih.gov/pubmed/37507201 http://dx.doi.org/10.1136/ard-2023-224068 |
work_keys_str_mv | AT triailleclement diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT tilmangaelle diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT sokolovatatiana diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT loriotaxelle diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT marchandisejoelle diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT demontjoyestephanie diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT nzeusseutoukapadrien diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT mericdebellefonlaurent diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT bouzincaroline diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT galantchristine diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT durezpatrick diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT lauwerysbernardr diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis AT limayenisha diseaseactivitydrivestranscriptomicheterogeneityinearlyuntreatedrheumatoidsynovitis |