The etiology of rheumatoid arthritis

Scherer, Hans Ulrich; Häupl, Thomas; Burmester, Gerd R.

doi:10.1016/j.jaut.2019.102400

Cited by 494 publications

(372 citation statements)

References 175 publications

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“…Osteoarthritis (OA) is the primary joint disorder and a major cause of disability, affecting 303 million people globally in 2017 [24,25]. The etiology, pathology and regenerative therapy have been wildly studied [26][27][28][29]. Also utilizing the single-cell platform, there were two nice reports that systematically uncovered the cell atlas and transcriptional regulation mechanisms of OA [30,31].…”

Section: Discussionmentioning

confidence: 99%

Systematic Study of Single-Cell Isolation from Musculoskeletal Tissues for Single-Cell Sequencing

Guo¹,

Liu²,

Zhang³

et al. 2020

Preprint

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Background: The single-cell platform provided revolutionary way to study cellular biology. Technologically, a sophistic protocol of isolating qualified single cells would be key to deliver to single-cell platform, which requires high cell viability, high cell yield and low content of cell aggregates or doublets. For musculoskeletal tissues, like bone, cartilage, nucleus pulposus, tendons, etc. as well as their pathological state, which are tense and dense, it’s full of challenge to efficiently and rapidly prepare qualified single-cell suspension. Conventionally, enzymatic dissociation methods were wildly used but lack of quality control. In the present study, we designed specific enzymatic treatment protocols for several human pathological musculoskeletal tissues, including degenerated nucleus pulposus, ossifying posterior longitudinal ligament and knee articular cartilage with osteoarthritis, aiming to rapidly and efficiently harvest qualified single-cell suspensions to meet the requirements of single-cell RNA-sequencing (scRNA-seq).Results: The single-cell suspensions from human degenerated nucleus pulposus and ossifying posterior longitudinal ligaments were both qualified after systematic quality control. Bioanalyzer trace showed expected cDNA size distribution of the scRNA-seq library. A clear separation of cellular barcodes from background partitions were verified by the barcode-rank plot after sequencing. However, we failed to obtain eligible samples from articular cartilage due to low cell viability and excessive cell aggregates and doublets. Conclusions: In conclusion, we provided rapid and efficient single-cell isolation protocols for human degenerated nucleus pulposus and ossifying posterior longitudinal ligament, which could be applied for scRNA-seq. More efforts will be made on improving the protocols for human articular cartilage.

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Section: Discussionmentioning

confidence: 99%

Systematic Study of Single-Cell Isolation from Musculoskeletal Tissues for Single-Cell Sequencing

Guo¹,

Liu²,

Zhang³

et al. 2020

Preprint

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“…RA is more common in northern Europe and North America, with predominance among women and elderly [1]. Previous studies suggest an interplay between genetic factors, environmental factors, and the immune system [2][3][4] although the pathogenesis of RA is still not fully understood. In families containing RA individuals, the majority of first-degree relatives (FDRs) never develop RA, even if they display risk factors such as smoking, anti-citrullinated protein antibodies (ACPAs), or carriage of HLA-shared epitope.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

et al. 2020

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Objective Recent studies have demonstrated an altered expression of certain microRNAs in patients with rheumatoid arthritis (RA) as well as their first-degree relatives (FDRs) compared to healthy controls (HCs), suggesting a role of microRNA in the progression of the disease. To corroborate this, a set of well-characterized RA families originating from northern Sweden were analyzed for differential expression of a selected set of microRNAs. Method MicroRNA was isolated from frozen peripheral blood cells obtained from 21 different families and included 26 RA patients, 22 FDRs, and 21 HCs. Expression of the selected microRNAs miR-22-3p, miR-26b-5p, miR-34a-3p, miR-103a-3p, miR-142-3p, miR-146a-5p, miR-155, miR-346, and miR-451a was determined by a two-step quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis including clinical variables was applied. Results Out of the nine selected microRNAs that previously have been linked to RA, we confirmed four after adjusting for age and gender, i.e., miR-22-3p (p = 0.020), miR-26b-5p (p = 0.018), miR-142-3p (p = 0.005), and miR-155 (p = 0.033). Moreover, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs. In addition, analysis of the effect of corticosteroid use showed modulation of miR-103a-3p expression. Conclusions We confirm that microRNAs seem to be involved in the development of RA, and that the expression pattern in FDR is partly overlapping with RA patients. The contribution of single microRNAs in relation to the complex network including all microRNAs and other molecules is still to be revealed. Key Points• Expression levels of miR-22-3p, miR-26b-5p, miR-142-3p, and miR-155 were significantly altered in RA patients compared to those in controls.• In first-degree relatives, a significant trend with an intermediate microRNA expression in FDR was observed for the same four microRNAs.

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“…Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease characterised by synovial inflammation and progressive joint destruction. 1 As known, activated T cells play a central role in the pathogenesis of RA. 2 Full T cell activation requires at least two signals, the initial recognition of the T cell receptor to its antigen presented by major histocompatibility complex (MHC) on antigen-presenting cells (APCs), followed by a second costimulatory signal accomplished by the binding of cluster of differentiation (CD)80 and/or CD86 on the surface of APCs to the CD28 receptor on T cells.…”

Section: Introductionmentioning

confidence: 99%

Response to abatacept is associated with the inhibition of proteasome β1i expression in T cells of patients with rheumatoid arthritis

et al. 2020

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ObjectiveAbatacept is a biological disease-modifying antirheumatic drug (DMARD) used for the treatment of rheumatoid arthritis (RA) and modulates the costimulatory signal by cluster of differentiation (CD)28:CD80/CD86 interaction required for T cell activation. Since CD28-mediated signalling regulates many T cell functions including cytokine production of, for example, interferons (IFNs), it is of interest to clarify, whether response to abatacept has an effect on the IFN inducible immunoproteasome, as a central regulator of the immune response.MethodsEffects of abatacept on the proteasome were investigated in 39 patients with RA over a period of 24 weeks. Using real-time PCR, transcript levels of constitutive and corresponding immunoproteasome catalytic subunits were investigated at baseline (T0), week 16 (T16) and week 24 (T24) in sorted blood cells. Proteasomal activity and induction of apoptosis after proteasome inhibition were also evaluated.ResultsAbatacept achieved remission or low disease activity in 55% of patients at T16 and in 70% of patients at T24. By two-way analysis of variance (ANOVA), a significant reduction of proteasome immunosubunit β1i was shown only in CD4+ and CD8+ T cells of sustained responders at both T16 and T24. One-way ANOVA analysis for each response group confirmed the results and showed a significant reduction at T24 in CD4+ and CD8+ T cells of the same group. Abatacept did not influence chymotrypsin-like activity of proteasome and had no effect on induction of apoptosis under exposure to a proteasome inhibitor in vitro.ConclusionThe reduction of proteasome immunosubunit β1i in T cells of patients with RA with sustained response to abatacept suggests association of the immunoproteasome of T cells with RA disease activity.

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The etiology of rheumatoid arthritis

Cited by 494 publications

References 175 publications

Systematic Study of Single-Cell Isolation from Musculoskeletal Tissues for Single-Cell Sequencing

Systematic Study of Single-Cell Isolation from Musculoskeletal Tissues for Single-Cell Sequencing

Dysregulated microRNA expression in rheumatoid arthritis families—a comparison between rheumatoid arthritis patients, their first-degree relatives, and healthy controls

Response to abatacept is associated with the inhibition of proteasome β1i expression in T cells of patients with rheumatoid arthritis

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