Heterogeneity of Synovial Molecular Patterns in Patients with Arthritis

Lauwerys, Bernard; Hernández-Lobato, Daniel; Gramme, Pierre; Ducreux, Julie; Dessy, Adrien; Focant, Isabelle; Ambroise, Jérôme; Bearzatto, Bertrand; Toukap, A. Nzeusseu; Eynde, Benoı̂t J. Van den; Elewaut, Dirk; Gala, Jean Luc; Durez, Patrick; Houssiau, Frédéric; Helleputte, Thibault; Dupont, Pierre

doi:10.1371/journal.pone.0122104

Cited by 29 publications

(23 citation statements)

References 19 publications

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“…Datasets with samples of 4 anatomical structures of knee joint, including cartilage, synovial tissues, meniscal tissues, and subchondral bone, can be found in GEO. 17 studies were selected in this study, including 3 studies in knee cartilage, 10 studies in knee synovial tissue, 3 studies in knee meniscal tissue, and 1 study in knee subchondral bone (Table 1) [22][23][24][25][26][27][28][29][30][31]. By integrated analysis, 12945 genes for cartilage, 3238 genes for synovial tissue, 6598 genes for meniscal tissue, and 9570 genes for subchondral bone were obtained.…”

Section: Resultsmentioning

confidence: 99%

The Immune Cell Landscape in Different Anatomical Structures of Knee in Osteoarthritis: A Gene Expression-Based Study

Chen

Deng

et al. 2020

BioMed Research International

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Background. Immunological mechanisms play a vital role in the pathogenesis of knee osteoarthritis (KOA). Moreover, the immune phenotype is a relevant prognostic factor in various immune-related diseases. In this study, we used CIBERSORT for deconvolution of global gene expression data to define the immune cell landscape of different structures of knee in osteoarthritis. Methods and Findings. By applying CIBERSORT, we assessed the relative proportions of immune cells in 76 samples of knee cartilage, 146 samples of knee synovial tissue, 40 samples of meniscus, and 50 samples of knee subchondral bone. Enumeration and activation status of 22 immune cell subtypes were provided by the obtained immune cell profiles. In synovial tissues, the differences in proportions of plasma cells, M1 macrophages, M2 macrophages, activated dendritic cells, resting mast cells, and eosinophils between normal tissues and osteoarthritic tissues were statistically significant (P<0.05). The area under the curve was relatively large in resting mast cells, dendritic cells, and M2 macrophages in receiver operating characteristic analyses. In subchondral bones, the differences in proportions of resting master cells and neutrophils between normal tissues and osteoarthritic tissues were statistically significant (P<0.05). In subchondral bones, the proportions of immune cells, from the principle component analyses, displayed distinct group-bias clustering. Resting mast cells and T cell CD8 were the major component of first component. Moreover, we revealed the potential interaction between immune cells. There was almost no infiltration of immune cells in the meniscus and cartilage of the knee joint. Conclusions. The immune cell composition in KOA differed substantially from that of healthy joint tissue, while it also differed in different anatomical structures of the knee. Meanwhile, activated mast cells were mainly associated with high immune cell infiltration in OA. Furthermore, we speculate M2 macrophages in synovium and mast cells in subchondral bone may play an important role in the pathogenesis of OA.

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Section: Resultsmentioning

confidence: 99%

The Immune Cell Landscape in Different Anatomical Structures of Knee in Osteoarthritis: A Gene Expression-Based Study

Chen

Deng

et al. 2020

BioMed Research International

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“…Osteoarthritis (OA) is increasingly recognised as a highly heterogeneous group of diseases characterised by variable clinical phenotypes 1,2 . OA heterogeneity underlines the various responses to current therapies for individual patients and inconsistency of outcomes observed in clinical practice 1,2 . There is, therefore, an urgent need to differentiate between distinct clinical phenotypes, especially in the early stages of the disease and progressive phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis

Kriegová

Manukyan

Mikulkova

et al. 2018

Osteoarthritis and Cartilage

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Based on the immune cell composition of SFs, data mining analysis revealed distinct phenotypes (monocyte- and lymphocyte-predominant) within each gender group. This first study on the cellular complexity of SFs in KOA showed marked differences between male and female patients. The findings give a rational starting point for patient stratification according to their phenotypes, as is required for phenotype-specific treatment strategies.

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“…Using high-density and customized low-density gene expression platforms, we also found heterogeneous expression of T cell (lymphoid)-associated transcripts in RA synovial tissue. In a group of 32 biopsies obtained in treated and untreated patients, we observed that expression of these transcripts displayed a significant, albeit moderate (0.40 < r <0.55) correlation with disease activity (disease activity score in 28 joints-C reactive protein (DAS28-CRP)) [ 3 , 4 ]. In other studies, we evaluated the effects of therapies on global gene expression patterns in prospective synovial biopsy samples obtained prior to and 3 months after initiation of therapy with methotrexate, tocilizumab, rituximab or adalimumab.…”

Section: Introductionmentioning

confidence: 99%

Higher expression of TNFα-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy

Groof¹,

Ducreux²,

Humby³

et al. 2016

Arthritis Res Ther

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BackgroundIL6-related T cell activation and TNFα-dependent cell proliferation are major targets of therapy in the RA synovium. We investigated whether expression of these pathways in RA synovial biopsies is associated with disease activity and response to therapy.MethodCorrelation and gene set enrichment studies were performed using gene expression profiles from RA synovial biopsies. Immunostaining experiments of GADD45B and PDE4D were performed on independent additional sets of early untreated RA samples, obtained in two different centers by needle-arthroscopy or US-guided biopsies.ResultsIn 65 RA synovial biopsies, transcripts correlating with disease activity were strongly enriched in TNFα-induced genes. Out of the individual variables used in disease-activity scores, tender joint count, swollen joint count and physician’s global assessment, but not CRP or patient’s global assessment displayed a similar correlation with the expression of TNFα-dependent genes. In addition, TNFα-induced genes were also significantly enriched in transcripts over-expressed in synovial biopsy samples obtained from poor-responders to methotrexate or tocilizumab, prior to initiation of therapy.GADD45B (induced by TNFα in monocytes) and PDE4D (induced by TNFα in FLS) immunostaining was significantly higher in overall poor-responders to therapy in 46 independent baseline samples obtained from early untreated RA patients prior to initiation of therapy. GADD45B (but not PDE4D) immunostaining was significantly higher in the sub-group of patients with poor-response to methotrexate therapy, and this was confirmed in another population of methotrexate-treated patients.ConclusionHigher expression of TNFα-induced transcripts in early RA synovitis is associated with higher disease activity, and predicts poor response to first-line therapy. That over-expression of TNFα-induced genes predicts poor-response to therapy regardless of the drug administered, indicates that this molecular signature is associated with disease severity, rather than with specific pathways of escape to therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0919-z) contains supplementary material, which is available to authorized users.

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Heterogeneity of Synovial Molecular Patterns in Patients with Arthritis

Cited by 29 publications

References 19 publications

The Immune Cell Landscape in Different Anatomical Structures of Knee in Osteoarthritis: A Gene Expression-Based Study

The Immune Cell Landscape in Different Anatomical Structures of Knee in Osteoarthritis: A Gene Expression-Based Study

Gender-related differences observed among immune cells in synovial fluid in knee osteoarthritis

Higher expression of TNFα-induced genes in the synovium of patients with early rheumatoid arthritis correlates with disease activity, and predicts absence of response to first line therapy

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