Single RNA-Seq of synovial tissue macrophages from Rheumatoid Arthritis patients with active disease and in disease remission.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000, NextSeq 500
ORGANISM(S): Homo sapiens
SUBMITTER: Thomas Otto Otto
PROVIDER: E-MTAB-8322 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2020-04-18 | E-MTAB-8873 | biostudies-arrayexpress
Project description:Mast cells are phenotypically and functionally highly heterogeneous, and their state is possibly controlled by their local microenvironment. Therefore, concrete analyses are needed to understand whether mast cells act as powerful motivators or dispensable bystanders in specific diseases. Here, we evaluated the correlation between synovial mast cells and rheumatoid arthritis (RA) disease severity, and the efficacy of therapeutic interventions against mast cells. We showed that degranulation of mast cells in inflammatory synovial tissues of RA patients was induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II (MHC II) and costimulatory molecules on mast cells were upregulated. These unique signaling response led to mast cell activation and promoted T cell responses, resulting in the progression of RA. Collagen-induced arthritis mouse models treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, showed significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to RA and may provide a novel mast cell-targeting therapy for RA.
2024-01-07 | PXD038584 | Pride
Project description:Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines & chemokines (e.g. IL-6, IL-7, IL-22, CCL8, CCL11, CCL13, CCL19, CCL20), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared to Methotrexate, Rituximab, or Adalimumab therapies. By opposition to the effects of Adalimumab, Tocilizumab therapy does not induce a decreased expression of genes involved in cell proliferation. Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. SDAI remission criteria were computed prospectively before, 3 months and 6 months after administration of the drugs and patientsM-bM-^@M-^Y responses were defined according to their SDAI remission status at 6 months. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 arrays.
2013-12-30 | E-GEOD-45867 | biostudies-arrayexpress
Project description:Synovial biopsies were taken using 14G Precisa Needle (HS Hospital Service, Italy) in ultrasound-guided protocol, and digested as described previously (Alivernini et al, 2020). Live CD45+ cells from the synovial tissue (ST) of healthy donors (n=3), patients with active RA (n=5) and patients in sustained remission (n=2) were sorted for single cell RNA (scRNA) or CITE (scCITE) sequencing using the 10x Genomics platform. Maximum 20,000 immune cells from tissue were sorted into Protein LoBind 1.5 ml Eppendorf tube containing 300 μl of RPMI media with 10% of FSC. Cells were loaded onto a Chromium Controller (10X Genomics) for single-cell partitioning, followed by library preparation using Single-Cell 3’ Reagent Kits v3.1. For 3 healthy ST and 4 ST from active RA (Figure S1), Totalseq Hashtag were used (Biolegend #394601, #394603, #394605, #394607, #394609) to combine 2 samples per run, and TotalSeq™-A Human Universal Cocktail (V1.0) was used to collect protein expression (CITEseq) data together with transcriptome data. Single-cell libraries were sequenced on the Illumina HiSeq 4000 system to a minimum depth of 50k reads/cell.
2024-12-06 | E-MTAB-14213 | biostudies-arrayexpress
Project description:Gene expression microarray was applied to discover novel rheumatoid arthritis (RA)-specific gene expressions by comparing the expression profiles of synovial membranes from patients with RA, osteoarthritis (OA) and ankylosing spondylitis (AS). We performed a gene expression microarray analysis of RA synovial membranes and simultaneously compared the expression profile with the profiles of AS and OA synovial membranes. This study was undertaken to investigate the global gene expression profiles in synovial tissues from RA (n=10), OA (n=7), and AS patients (n=5). The Illumina HumanHT-12 v4 Expression BeadChip were used for a complete genome-wide transcript profiling.
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