Correspondence on 'Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis'.
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SUBMITTER: Dumoulin QA
PROVIDER: S-EPMC7615881 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Correspondence on 'Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis'.
Dumoulin Quirine A QA Matthijssen Xanthe M E XME Wouters Fenne F Krijbolder Doortje I DI Niemantsverdriet Ellis E van der Helm-van Mil Annette H M AHM
Annals of the rheumatic diseases 20210705 7
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Project description:BackgroundHyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA).MethodsWe used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis.ResultsCompared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs.ConclusionsThe levels, composition, and MW distribution of all currently known lubricants in SF--HA, lubricin, PLs--vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction.
| S-EPMC4416892 | biostudies-literature
Project description:Formation of autoantibodies to carbamylated proteins (anti-CarP) is considered detrimental in the prognosis of erosive rheumatoid arthritis (RA). The source of carbamylated antigens and the mechanisms by which anti-CarP antibodies promote bone erosion in RA remain unknown. Here, we find that neutrophil extracellular traps (NETs) externalize carbamylated proteins and that RA subjects develop autoantibodies against carbamylated NET (cNET) antigens that, in turn, correlate with levels of anti-CarP. Transgenic mice expressing the human RA shared epitope (HLADRB1* 04:01) immunized with cNETs develop antibodies to citrullinated and carbamylated proteins. Furthermore, anti-carbamylated histone antibodies correlate with radiographic bone erosion in RA subjects. Moreover, anti-carbamylated histone-immunoglobulin G immune complexes promote osteoclast differentiation and potentiate osteoclast-mediated matrix resorption. These results demonstrate that carbamylated proteins present in NETs enhance pathogenic immune responses and bone destruction, which may explain the association between anti-CarP and erosive arthritis in RA.
| S-EPMC7608797 | biostudies-literature
Project description:Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have key differences in clinical presentation, radiographic findings, comorbidities and pathogenesis to distinguish between these common forms of chronic inflammatory arthritis. Joint involvement is typically, but not always, asymmetric in PsA, while it is predominantly symmetric in RA. Bone erosions, without new bone growth, and cervical spine involvement are distinctive of RA, while axial spine involvement, psoriasis and nail dystrophy are distinctive of PsA. Patients with PsA typically have seronegative test findings for rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies, while approximately 80% of patients with RA have positive findings for RF and CCP antibodies. Although there is overlap in the pathogenesis of PsA and RA, differences are also present that affect the efficacy of treatment. In PsA, levels of interleukin (IL)-1?, IL-6, IL-17, IL-22, IL-23, interferon-? and tumour necrosis factor-? (TNF-?) are elevated, and in RA, levels of IL-1, IL-6, IL-22, IL-33, TNF-?, chemokine ligand 11 and chemokine C-X-C motif ligand 13 are elevated. Differences in the pathogenesis of RA and PsA translate into some variances in the specificity and efficacy of therapies.
| S-EPMC6109814 | biostudies-literature
Project description:ObjectiveRheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis. Intra-articular gene delivery to block proinflammatory cytokines has been studied in pre-clinical models and human clinical trials. It has been demonstrated that the level of programmed death-ligand 1 (PD-L1) is associated with rheumatoid arthritis (RA). This study examined the therapeutic role of PD-L1 by intra-articular delivery via adeno-associated virus (AAV) vectors in the mouse collagen-induced arthritis (CIA) model.MethodsMice were intra-articularly injected with AAV5 vectors encoding human PD-L1 on day 0 and immunized with bovine type II collagen to induce CIA simultaneously. On day 49 post AAV administration, joints were collected for histo-pathological and cytokine analysis. Additionally, the systemic impacts of intra-articular injection of AAV5/PD-L1 vectors were also studied. To study the therapeutic effect of PD-L1, AAV5/PD-L1 vectors were administered into the joints of RA mice on day 21.ResultsAfter administration of AAV5/PD-L1 vectors, strong PD-L1 expression was detected in AAV transduced joints. Joints treated with PD-L1 at the time of arthritis induction exhibited significantly less swelling and improved histopathological scores when compared to untreated joints. Additionally, the infiltration of T cells and macrophages was decreased in joints of CIA mice that received AAV5/PD-L1 vectors (P<0.05). The levels of pro-inflammatory cytokines, including IL-1, IL-6, IL-17 and TNFα, were lower in AAV5/PD-L1 treated than untreated joints (P<0.05). Furthermore, the administration of AAV5/PD-L1 vectors into the joints of CIA mice did not impact serum cytokine levels and the antibody titers to type II collagen. Biodistribution of AAV vectors after intra-articular injection showed undetectable AAV genomes in other tissues except for a low level in the liver. Similar to the results of AAV5/PD-L1 vector administration on day 0, decreased joint swelling and lower histopathological damage were observed in joints treated with AAV5/PD-L1 vectors on day 21.ConclusionThe results from this study demonstrate that local AAV mediated PD-L1 gene delivery into the joints is able to prevent the development and block the progression of arthritis in CIA mice without impacting systemic immune responses. This study provides a novel strategy to effectively treat inflammatory joint diseases using local AAV gene therapy by interference with immune checkpoint pathways.
| S-EPMC10021025 | biostudies-literature
Project description:BackgroundLimited information exists comparing the perioperative complications of the different inflammatory arthropathies (IAs) after total hip arthroplasty (THA). Our study was aimed to (1) compare perioperative complications and (2) determine the most common complications between the different IA subtypes compared with patients with primary osteoarthritis (OA) undergoing primary THA and (3) find whether the difference in postoperative complications also exists between different IA after THA.MethodsThe Nationwide Inpatient Sample (NIS) was used to identify patients with Rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis (AS), and primary OA undergoing unilateral THA between 2005 and 2014. Preoperative diagnosis, comorbidities, and postoperative complications were determined using the International Classification of Disease Clinical Modification version 9 codes. The prevalence of perioperative complications was compared between patients with IA and primary OA and between patients with different IA.ResultsWhen compared with patients with primary OA, patients with RA had significantly more postoperative surgical and medical complications. Yet there are just several medical complications differences exist between PA and primary OA or AS and primary OA, including stroke and acute renal failure for psoriatic arthritis and urinary tract infection and pneumonia for AS. What is more, there were also several differences in perioperative medical complications seen in patients with different IA.ConclusionExcept for patients with RA, the differences in perioperative complications was small between patients with IA and primary OA and between patients with different types of IA.
| S-EPMC9580196 | biostudies-literature
Project description:BackgroundAutoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse. Here, we aimed to evaluate the incidence of TAbs in a consecutive Chinese RA cohort and to investigate whether the elevated presence of TAbs is associated with joint damage and synovitis in RA patients.MethodsA total of 125 hospitalized RA patients were consecutively recruited. Clinical data and available synovial tissues were collected at baseline, and TAbs and thyroid function were detected by chemiluminescent immunoassay. Patients who tested positive for TPOAbs or TgAbs were classified as the TAbs-positive group, and patients who tested positive for neither TPOAbs nor TgAbs were recruited as the TAbs-negative group. Disease activity was assessed using DAS28-ESR (the disease activity score in 28 joints and including the erythrocyte sedimentation rate). X-ray assessment of the hand/wrist was performed according to the Sharp/van der Heijde-modified Sharp score (mTSS), and patients with an mTSS score >10 were defined as having radiographic joint damage (RJD). Serial tissue sections were stained immunohistochemically for CD3, CD15, CD20, CD34, CD38, and CD68, and synovitis were assessed according to Krenn's synovitis score.ResultsA total of 44 (35%) patients were positive for either TPOAbs or TgAbs. Importantly, there was a significantly greater percentage of patients with RJD in the TAbs-positive group versus the TAbs-negative group (68% vs. 42%, p = 0.005). Compared with the TAbs-negative group, significantly more CD38-positive plasma cells infiltrated the TAbs-positive synovium, and a higher percentage of patients with high-grade synovitis were observed in the TAbs-positive group (5/8, 63% vs. 5/14, 36%). Moreover, RF positivity and disease activity indicators, including TJC28, DAS28-ESR, and CDAI, were significantly higher in the TAbs-positive group (all p < 0.05). Adjusted logistic regression analysis revealed that positive TAbs (OR 2.999, 95% CI [1.301-6.913]; p = 0.010) and disease duration (OR 1.013, 95% CI [1.006-1.019]; p < 0.001) were independently associated with RJD, and an odds ratio of 2.845 (95% CI [1.062-7.622]) was found for RJD in women with positive TAbs (n = 37) compared with those without TAbs (n = 59) (p = 0.038).ConclusionOur data showed that joint destruction was amplified in RA patients with an elevated presence of TAbs, which supports the importance and necessity of TAbs and thyroid function screening and monitoring in RA patient management in clinical practice.
| S-EPMC5756613 | biostudies-literature
Project description:ObjectiveTo investigate pain course over time and to identify baseline and 3-month predictors of unacceptable pain with or without low inflammation in early RA.MethodsA cohort of 275 patients with early RA, recruited in 2012-2016, was investigated and followed for 2 years. Pain was assessed using a visual analogue scale (VAS; 0-100 mm). Unacceptable pain was defined as VAS pain >40, and low inflammation as CRP <10 mg/l. Baseline and 3-month predictors of unacceptable pain were evaluated using logistic regression analysis.ResultsAfter 2 years, 32% of patients reported unacceptable pain. Among those, 81% had low inflammation. Unacceptable pain, and unacceptable pain with low inflammation, at 1 and 2 years was significantly associated with several factors at 3 months, but not at baseline. Three-month predictors of these pain states at 1 and 2 years were higher scores for pain, patient global assessment, and the health assessment questionnaire, and more extensive joint tenderness compared with the number of swollen joints. No significant associations were found for objective inflammatory measures.ConclusionA substantial proportion of patients had unacceptable pain with low inflammation after 2 years. Three months after diagnosis seems to be a good time-point for assessing the risk of long-term pain. The associations between patient reported outcomes and pain, and the lack of association with objective inflammatory measures, supports the uncoupling between pain and inflammation in RA. Having many tender joints, but more limited synovitis, may be predictive of long-term pain despite low inflammation in early RA.
| S-EPMC10907811 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is characterized by synovial joint inflammation, cartilage damage, and dysregulation of the adaptive immune system. While neutrophil extracellular traps (NETs) have been proposed to play a role in the generation of modified autoantigens and in the activation of synovial fibroblasts, it remains unknown whether NETs are directly involved in cartilage damage. Here, we report a new mechanism by which NET-derived elastase disrupts cartilage matrix and induces release of membrane-bound peptidylarginine deiminase-2 by fibroblast-like synoviocytes (FLSs). Cartilage fragments are subsequently citrullinated, internalized by FLSs, and then presented to antigen-specific CD4+ T cells. Furthermore, immune complexes containing citrullinated cartilage components can activate macrophages to release proinflammatory cytokines. HLA-DRB1*04:01 transgenic mice immunized with NETs develop autoantibodies against citrullinated cartilage proteins and display enhanced cartilage damage. Inhibition of NET-derived elastase rescues NET-mediated cartilage damage. These results show that NETs and neutrophil elastase externalized in these structures play fundamental pathogenic roles in promoting cartilage damage and synovial inflammation. Strategies targeting neutrophil elastase and NETs could have a therapeutic role in RA and in other inflammatory diseases associated with inflammatory joint damage.
| S-EPMC7406272 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to systemic and articular bone loss by activating bone resorption and suppressing bone formation. Despite current therapeutic agents, inflammation-induced bone loss in RA continues to be a significant clinical problem due to joint deformity and lack of articular and systemic bone repair. Here, we identify the suppressor of bone formation, Schnurri-3 (SHN3), as a potential target to prevent bone loss in RA. SHN3 expression in osteoblast-lineage cells is induced by proinflammatory cytokines. Germline deletion or conditional deletion of Shn3 in osteoblasts limits articular bone erosion and systemic bone loss in mouse models of RA. Similarly, silencing of SHN3 expression in these RA models using systemic delivery of a bone-targeting recombinant adenoassociated virus protects against inflammation-induced bone loss. In osteoblasts, TNF activates SHN3 via ERK MAPK-mediated phosphorylation and, in turn, phosphorylated SHN3 inhibits WNT/β-catenin signaling and up-regulates RANKL expression. Accordingly, knock-in of a mutation in Shn3 that fails to bind ERK MAPK promotes bone formation in mice overexpressing human TNF due to augmented WNT/β-catenin signaling. Remarkably, Shn3-deficient osteoblasts are not only resistant to TNF-induced suppression of osteogenesis, but also down-regulate osteoclast development. Collectively, these findings demonstrate SHN3 inhibition as a promising approach to limit bone loss and promote bone repair in RA.
| S-EPMC10175794 | biostudies-literature
Project description:IntroductionThe western population is ageing. It is unknown whether age at diagnosis affects the severity of Rheumatoid Arthritis (RA), we therefore performed the present study.Method1,875 RA-patients (7,219 radiographs) included in five European and North-American cohorts (Leiden-EAC, Wichita, Umeå, Groningen and Lund) were studied on associations between age at diagnosis and joint damage severity. In 698 Leiden RA-patients with 7-years follow-up it was explored if symptom duration, anti-citrullinated-peptide-antibodies (ACPA), swollen joint count (SJC) and C-reactive-protein (CRP) mediated the association of age with joint damage. Fifty-six other RA-patients of the EAC-cohort underwent baseline MRIs of wrist, MCP and MTP-joints; MRI-inflammation (RAMRIS-synovitis plus bone marrow edema) was also evaluated in mediation analyses. Linear regression and multivariate normal regression models were used.ResultsAnalysis on the five cohorts and the Leiden-EAC separately revealed 1.026-fold and 1.034-fold increase of radiographic joint damage per year increase in age (β=1.026, 1.034, both p<0.001); this effect was present at baseline and persisted over time. Age correlated stronger with baseline erosion-scores compared to joint space narrowing (JSN)-scores (r=0.38 versus 0.29). Symptom duration, ACPA, SJC and CRP did not mediate the association of age with joint damage severity. Age was significantly associated with the MRI-inflammation-score after adjusting for CRP and SJC (β=1.018, p=0.027). The association of age with joint damage (β=1.032, p=0.004) decreased after also including the MRI-inflammation-score (β=1.025, p=0.021), suggesting partial mediation.ConclusionRA-patients presenting at higher age have more severe joint damage; this might be partially explained by more severe MRI-detected inflammation at higher age.
| S-EPMC4547419 | biostudies-literature