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ID PMID Title PublicationDate abstract
30938551 Clinical features and human T-cell leukemia virus type-1 (HTLV-1) proviral load in HTLV-1- 2020 May Objective: Recently, Human T-cell leukemia virus type-1 proviral load (HTLV-1 PVL) has been evaluated as an important predictor of adult T-cell leukemia/lymphoma (ATL) in HTLV-1 carriers. We aimed to evaluate whether HTLV-1 PVL is also important for the development of ATL among HTLV-1-positive patients with rheumatoid arthritis (RA).Methods: We established a cohort of 82 HTLV-1-positive RA patients between 2017 and 2018. Of those, 27 (32.9%) were treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) with/without methotrexate. We measured HTLV-1 PVL in peripheral blood mononuclear cells (PBMCs) at study entry and compared the value by clinical status and treatment options.Results: The median PVL for all was 9.6 copies per 1000 PBMCs without sex difference (male 17.2 and female 8.6; p = .24). The median PVL was significantly higher for patient's comorbid bronchiectasis, malignancies, and opportunistic infectious diseases, compared with patients without comorbidity. There were no significant differences in PVL levels among types of bDMARDs, although the level was tended to be higher for patients treated with JAK inhibitor.Conclusions: HTLV-1 seropositive RA patients comorbid for any diseases having higher HTLV-1 PVLs will be a higher risk for developing ATL. Careful follow-up of these patients is necessary to detect ATL development.
32281551 Osteoimmunology - Bidirectional dialogue and inevitable union of the fields of bone and im 2020 Bone is a critically important part of the skeletal system that is essential for body support and locomotion. The immune system protects against pathogens and is active in host defense. These two seemingly distinct systems in fact interact with each other, share molecules and create a collaborative regulatory system called the "osteoimmune system". The most representative osteoimmune molecule is receptor activator of NF-κB ligand (RANKL), which plays multiple roles in the osteoimmune system under both physiological and pathological conditions such as rheumatoid arthritis and cancer metastasis to bone. Based on accumulating evidence for such mutual dependence, it is concluded that the relationship between bone and the immune system did not develop by accident but as a necessary consequence of evolution. Here I describe the history of and recent advances in osteoimmunology, providing a perspective in the contexts of both science and medicine.
31309562 Syndecan-4 involves in the pathogenesis of rheumatoid arthritis by regulating the inflamma 2020 Feb Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and the pathogenesis of RA is still unknown. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) are of significance in the pathogenesis of RA. In this study, three microarray profiles (GSE55457, GSE55584, and GSE55235) of human joint FLSs from 33 RA patients and 20 normal controls were extracted from the Gene Expression Omnibus Dataset and analyzed to investigate the underlying pathogenesis of RA. As analyzed by the differently expressed genes, gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analysis, syndecan-4 (SDC4), a receptor of multiple cytokines and chemokines, which played a key role in the regulation of inflammatory response, was found to be an essential regulator in RA. To further validate these results, the levels of SDC4, reactive oxygen species (ROS), nitric oxide (NO), inflammation, and apoptosis in RA-FLSs were examined. SDC4-silenced RA-FLSs were also used. The results demonstrated that SDC4 and the level of ROS, NO, and inflammation were highly expressed while the apoptosis was decreased in RA-FLSs compared with normal FLSs. SDC4 silencing significantly suppressed the levels of ROS, NO, and inflammation; elevated the expression of nuclear factor erythroid 2-related factor 2; and promoted the apoptosis of RA-FLSs. Collectively, our results demonstrated a new mechanism of SDC4 in initiating the inflammation and inhibiting the apoptosis of RA-FLSs and that a potential target for the diagnosis and treatment of RA in the clinic might be developed.
33124165 Association between thiazolidinedione use and rheumatoid arthritis risk in patients with t 2021 Mar AIM: A previous study revealed that PPARγ agonists have anti-inflammatory effects in rheumatoid arthritis (RA). Furthermore, some studies have shown that type 2 diabetes mellitus (T2DM) may elicit the development of RA. In this study, we aimed to investigate whether the use of thiazolidinediones (TZDs) is associated with a lower risk of developing RA in patients with T2DM. METHODS: Based on the Taiwan National Health Insurance Research Database, we conducted a nationwide case-control study. The selected cases were patients with T2DM who were diagnosed with RA between 2000 and 2013. The controls were retrieved at a ratio of 1:4 by propensity score matching. Logistic regression was conducted to evaluate whether TZD use lowers the risk of RA in patients with T2DM. The dose-response effect was examined according to the total TZD dose, within 2 years before the index date (the first diagnosis date of RA), and TZD doses were divided into four groups by cumulative Defined Daily Dose (cDDD): <30, 31-90, 91-365, and >365 cDDDs. RESULTS: A total of 3605 cases and 14 420 controls were included in this study. After adjusting for age, sex, baseline comorbidities, the results demonstrated that TZD use did not significantly reduce the risk of RA in patients with T2DM (adjusted OR = 0.91, 95% CI 0.81-1.02). In the subgroup analysis by total TZD exposure dose within 2 years, 91-365 cDDDs of TZD had a lower risk of RA development, aOR = 0.87 (95% CI 0.71-1.06) and >365 cDDDs of TZD, aOR = 0.85 (95% CI 0.73-1.01). In the trend test, P was <.05. CONCLUSIONS: TZD use might reduce the risk of RA in patients with T2DM, but it was non-statistically significant. Further research is necessary to assess this association.
30680930 Reduction in Upper Limb Joint Surgery Among Rheumatoid Arthritis Patients: An Interrupted 2020 Feb OBJECTIVE: Joint replacement surgery is a proxy of severe joint damage in rheumatoid arthritis (RA). The aim of this study was to assess the impact of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the incidence rate (IR) of upper limb joint replacements among newly diagnosed RA patients. METHODS: Using the Danish National Patient Register, patients with incident RA from 1996-2012 were identified. Each patient was matched on age, sex, and municipality, with up to 10 general population controls. The age- and sex-standardized 5-year IR per 1,000 person-years of a composite outcome of any first joint replacement of the finger, wrist, elbow, or shoulder was calculated, and an interrupted time-series analysis was undertaken to investigate trends and changes of the IR in the pre-bDMARD (1996-2001) and the bDMARD eras (2003-2012), with a 1-year lag period in 2002. RESULTS: In total, 18,654 incident patients with RA were identified (mean age 57.6 years, 70.5% women). The IR of joint replacements among patients with RA was stable at 2.46 per 1,000 person-years (95% confidence interval [95% CI] 1.96, 2.96) from 1996 to 2001 but started to decrease from 2003 onwards (-0.08 per 1,000 person-years annually [95% CI -0.20, 0.02]). Compared with patients with RA, the IR among controls in 1996 was 1/17 and increased continuously throughout the study period. CONCLUSION: The IR of upper limb joint replacements started to decrease among patients with RA from 2002 onwards, whereas it increased among controls. Our results suggest an association between the introduction of bDMARDs and a lower need of joint replacements among patients with RA.
33490289 Blocking Interleukin-33 Alleviates the Joint Inflammation and Inhibits the Development of 2020 Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin-33 (IL-33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen-induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL-33-neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti-murine IL-33 antibody (anti-IL-33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti-IL-33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti-IL-33 treatment also significantly decreased the serum levels of interferon-γ(IFN-γ),IL-6, IL-12, IL-33, and tumor necrosis factor-α (TNF-α). Moreover, anti-IL-33 treatment significantly downregulated the production of IFN-γ, IL-6, IL-12, IL-33, and TNF-α in ex vivo-stimulated spleen cells. Together, our results indicate that the IL-33-neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.
32505094 Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthriti 2020 Sep Rheumatoid arthritis (RA) is a chronic, symmetric, systemic autoimmune disease. Because insufficient apoptosis of fibroblast-like synoviocytes (FLS) is an important characteristic of RA, promoting apoptosis is considered a potential therapeutic tool for treating RA. We have previously found that daphnetin (7,8-dihydroxycoumarin, DAP) has a pro-apoptotic effect on fibroblast-like synoviocytes from collagen-induced arthritis (CIA) rats. In the present study, we further investigated the mechanisms of DAP-induced apoptosis in CIA-FLS. CIA-FLS were incubated with DAP for 48 h in the presence or absence of caspase inhibitors, including inhibitors of caspase-3, caspase-8, or caspase-9 or a pan-caspase inhibitor; then, a series of experiments were performed to evaluate the mechanisms of DAP-induced apoptosis. Our results showed that DAP markedly decreased cell viability and induced the apoptosis of CIA-FLS along with typical morphological and ultrastructural changes; moreover, DAP increased FasL, cytochrome c (Cyt-c), Bax, caspase-3, caspase-8, and caspase-9 mRNA expression and Bax, caspase-3, caspase-8, and caspase-9 protein expression. In contrast, DAP decreased Bcl-2 mRNA and protein expression and promoted the release of Cyt-c from the mitochondria into the cytosol; these effects were attenuated to varying degrees by pre-treatment with caspase inhibitors, especially with caspase-3 or caspase-9 inhibitors or a pan-caspase inhibitor. In conclusion, the current findings demonstrate that the DAP-induced apoptosis of CIA-FLS occurred mainly via a caspase-dependent pathway, in particular the mitochondrial pathway, and that the Bax/Bcl-2 ratio was involved in this process. Thus, DAP may be a potential therapeutic agent for RA.
33168559 Relationship between dietary magnesium intake and rheumatoid arthritis in US women: a cros 2020 Nov 9 OBJECTIVES: Diet has been shown to be associated with rheumatoid arthritis (RA), and magnesium has been shown to inhibit inflammatory responses, but research on the relationship between dietary magnesium and RA is limited and controversial. In this study, we aimed to explore the non-linear relationship between dietary magnesium intake and RA in US women. DESIGN: Cross-sectional survey. SETTING: National Health and Nutrition Examination Survey (NHANES). PRIMARY AND SECONDARY OUTCOME MEASURES: Non-linear relationship between dietary magnesium intake and prevalence of RA. PARTICIPANTS: A total of 13 324 women aged 18-80 years (RA n=12 306, non-RA n=1018) were included in this study. RESULTS: Overall, the absolute risk (AR) of RA was 7.24% in all participants. In the multivariable logistic regression analysis, we found a negative correlation between dietary magnesium intake and RA (OR=0.84, 95% CI 0.75 to 0.95, p=0.006). When we converted dietary magnesium intake into a categorical variable (tertiles), the ARs of the low group, the middle group and the high group were 9%, 7.1% and 4.9%, respectively. We noticed that the ORs between the three groups were not equidistant; then, we detected a U-shaped linking by smooth curve fitting and obtained inflection points at 181 and 446 mg/day. The prevalence of RA decreased when dietary magnesium intake was <181 mg/day (OR=0.7, 95% CI 0.5 to 0.8, p<0.001) and increased when it was >446 mg/day (OR=2.8, 95% CI 1.2 to 6.6, p=0.020), remaining at a minimum when it was between 181 and 446 mg/day (OR=1.0, 95% CI 0.7 to 1.2, p=0.700). CONCLUSION: There was a U-shaped relationship between dietary magnesium and RA in women, and our study highlights the importance of moderate dietary magnesium intake in possibly exerting a protective role in women with RA.
32938290 A systematic review of outcomes of wrist arthrodesis and wrist arthroplasty in patients wi 2021 Mar Surgical management of end-stage rheumatoid wrists is a contentious topic. The standard surgical treatment has traditionally been wrist arthrodesis. Wrist arthroplasty, however, offers an alternative that preserves some wrist motion. A systematic review of MEDLINE, EMBASE and CENTRAL databases was conducted. Data from 23 studies representing 343 cases of wrist arthrodesis and 618 cases of wrist arthroplasty were included. Complication rates were 17% for arthrodesis and 19% for arthroplasty, and both procedures were effective at alleviating pain and improving grip strength. Functional assessment by Disabilities of the Arm, Shoulder, and Hand and Patient-Related Wrist Evaluation of arthroplasty patients revealed clinically meaningful functional improvement compared with preoperative measurements. In contrast to previously published findings both procedures demonstrated comparable complication rates. While this can be speculated to be from advancements in prosthetics, robust long-term follow-up data on wrist arthroplasty are not available yet.
32896694 Medicare expenditures for conventional and biologic disease modifying agents commonly used 2020 Oct BACKGROUND: Biologic disease modifying agents (bDMARDs) are an integral part of rheumatoid arthritis treatment guidelines but are associated with significant cost in the US. We present the trends in total spending and unit cost of conventional DMARDs (cDMARDs) as compared to bDMARDs in Medicare program. METHODS: We used the Medicare drug spending data for the year 2012-2017 covering all part B (fee-for-service) and part D drugs. Total spending was calculated by summing spending across various drug formulations and unit drug cost by dividing total spending by number of doses dispensed. We present the 6-year trends in total spending, total beneficiary count and unit costs of each of the commonly used cDMARDs and bDMARDs. RESULTS: Between 2012 and 2017, the total spending on the cDMARDs increased 5-folds from $98 million to $579 million; this was fraction of total spending on bDMARDs which increased from $4.3 to $10.0 billion. This increase was driven largely by unit costs of drug rather than number of beneficiaries. There was a 6-fold increase in the unit cost of generic hydroxychloroquine followed by methotrexate and leflunomide. Amongst bDMARDs, adalimumab and etanercept unit cost increased by 2-folds. The increase was less pronounced for office-administered products. CONCLUSIONS: Despite the availability of several generic cDMARDs over decades, there were steep increases in the unit cost of these agents to "keep pace" with the increases in bDMARDs. As the number of elderly rheumatoid arthritis patients increases, policy interventions might be required to reduce the spending on both biologics and conventional DMARDs.
32531503 Treatment-resistant synovitis and radiographic progression are increased in elderly-onset 2020 Aug BACKGROUND: Clinical outcomes in elderly-onset rheumatoid arthritis (EORA), starting after the age of 60, are conflicting. Thus, we aimed to investigate in a unique biopsy-driven, treatment-naïve early arthritis cohort, the relationship between synovial pathobiology of elderly- (EORA) and younger-onset rheumatoid arthritis (YORA) patients through clinical, imaging and treatment response outcome-measures. METHODS: Patients (n = 140) with early RA (<12months) starting before (YORA, n = 99) or after (EORA, n = 41) age 60 had an ultrasound-guided synovial biopsy prior to conventional immunosuppressive therapy and after 6 months. Clinical, ultrasound and radiographic data were collected prospectively and compared between groups and against immunohistological features. Using multivariate logistic regression, we determined predictors of clinical response (disease activity score-28-erythrocyte sedimentation rate [DAS28-ESR]<3.2) at 6 months and radiographic progression (≥1-unit-increase in Sharp van der Heijde [SvdH] score) at 12 months. RESULTS: EORA patients were more frequently male and presented most commonly with an abrupt, polymyalgia rheumatica-like onset and extra-articular features. Both before and after treatment, DAS28-ESR was similar but ultrasound synovial-thickening (p<0.05) and power-Doppler (p<0.01) synovitis and SvdH (p<0.001) scores were higher in EORA patients. EORA was independently associated with poor treatment response at 6 months (OR=0.28, p = 0.047) and radiographic progression at 12 months (OR=4.08, p = 0.029). Synovial pathotype, synovitis scores and cellular infiltration were similar before treatment, but a pauci-immune-fibroid pathotype tended to be more common in YORA at 6 months (p = 0.093). Moreover, YORA patients had a marked improvement of all synovitis parameters (p<0.001), whereas EORA presented only mild decreases in synovitis (p<0.05), sublining macrophage (p<0.05) and T cell scores (p<0.05), with no significant changes in lining macrophages, B cells or plasma cells. CONCLUSION: Early EORA presents differently and has a worse overall prognosis than YORA, with poorer clinical, histological, ultrasonographic and radiographic outcomes.
32475078 Latent Class Trajectory Modeling of 2-Component Disease Activity Score in 28 Joints Identi 2020 Oct OBJECTIVE: To determine whether using a reweighted disease activity score that better reflects joint synovitis, i.e., the 2-component Disease Activity Score in 28 joints (DAS28) (based on swollen joint count and C-reactive protein level), produces more clinically relevant treatment outcome trajectories compared to the standard 4-component DAS28. METHODS: Latent class mixed modeling of response to biologic treatment was applied to 2,991 rheumatoid arthritis (RA) patients in whom treatment with a biologic disease-modifying antirheumatic drug was being initiated within the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort, using both 4-component and 2-component DAS28 scores as outcome measures. Patient groups with similar trajectories were compared in terms of pretreatment baseline characteristics (including disability and comorbidities) and follow-up characteristics (including antidrug antibody events, adherence to treatments, and blood drug levels). We compared the trajectories obtained using the 4- and 2-component scores to determine which characteristics were better captured by each. RESULTS: Using the 4-component DAS28, we identified 3 trajectory groups, which is consistent with previous findings. We showed that the 4-component DAS28 captures information relating to depression. Using the 2-component DAS28, 7 trajectory groups were identified; among them, distinct groups of nonresponders had a higher incidence of respiratory comorbidities and a higher proportion of antidrug antibody events. We also identified a group of patients for whom the 2-component DAS28 scores remained relatively low; this group included a high percentage of patients who were nonadherent to treatment. This highlights the utility of both the 4- and 2-component DAS28 for monitoring different components of disease activity. CONCLUSION: Here we show that the 2-component modified DAS28 defines important biologic and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.
31192856 Prevalence for and Factors Associated With Depression and Anxiety Symptoms in Mexican Pati 2020 Oct BACKGROUND/OBJECTIVE: It has been suggested that patients with rheumatoid arthritis (RA) often present depression and anxiety. The objective of this study was to estimate the prevalence of depression and anxiety symptoms in Mexican patients with RA and to determine associated factors of depression and anxiety in this population. METHODS: This was a cross-sectional study. We evaluated demographic characteristics, medical comorbidities, substance use, and disease characteristics in 103 patients with RA. Patients were enrolled from March 2016 to August 2017 The prevalence of depression and anxiety was estimated using the Hospital Anxiety and Depression Scale. We calculated the proportion of depression and anxiety symptoms and compared characteristics between groups. Finally, logistic regression model was used to determine the factors associated with depression and anxiety. RESULTS: Depression symptoms were present in 26.2% of patients, whereas anxiety symptoms were present in 16.5% of patients. Presence of hypertension was an associated factor with depression (odds ratio [OR], 3.13; 95% confidence interval [CI], 1.06-9.23; p = 0.03). Low socioeconomic (OR, 3.78; 95% CI, 1.39-10.28; p = 0.009) and high scores of 28-joint Disease Activity Score were associated with anxiety (OR, 3.19; 95% CI, 1.20-8.45; p = 0.02). CONCLUSIONS: Factor related to socioeconomic conditions, comorbid medical conditions, and disease activity were related to the presence of clinical depression and anxiety in Mexican patients with RA, which may have a negative impact in the course and outcome of the disease. We suggest an early identification of depression and anxiety in these patients through an early psychiatric evaluation.
32852109 Improvements in Fatigue Lag Behind Disease Remission in Early Rheumatoid Arthritis: Result 2021 Jan OBJECTIVE: To examine the relationship between disease activity and fatigue over time in early rheumatoid arthritis (RA). METHODS: Data were from patients with early RA (duration of symptoms ≤12 months) enrolled in the Canadian Early Arthritis Cohort (CATCH). Patients rated their fatigue over the past week using an 11-point numerical rating scale (NRS) for up to 5 years of follow-up. Fatigue severity was classified as low (≤2), moderate (>2 but <5), or high (≥5). Differences in fatigue ratings in patients who achieved a low disease state (Disease Activity Score in 28 joints [DAS28] <3.2) and those who did not within 3-months of cohort entry were compared. RESULTS: Of 1,864 patients included, 88% met RA criteria, and 72% were women. The mean ± SD baseline DAS28 was 4.9 ± 1.5. Nineteen percent of the patients reported moderate baseline fatigue, and 59% reported severe baseline fatigue. Fatigue was correlated with pain and patient global ratings (r = 0.56-0.67, P < 0.001), and was weakly correlated with DAS28, tender joint count, swollen joint count, physician global assessment of disease activity, erythrocyte sedimentation rate, and C-reactive protein level. Patients who reported low fatigue by 3 months had significantly lower fatigue throughout follow-up compared to those who had moderate or high fatigue at 3 months (P < 0.001). Patients who achieved a DAS28 <3.2 within 3 months had significantly lower fatigue ratings (mean ± SD 2.7 ± 2.6) than those with a DAS28 >3.2 (4.6 ± 3.0) (P < 0.001), with improvements in fatigue that persisted through 5 years of follow-up. Maximal improvements in fatigue lagged behind remission by 6 months. CONCLUSION: Fatigue is common in early RA, and improvements may occur after remission. Early treatment response within 3-months was associated with short-term and long-term benefits in fatigue over time.
32352848 Experiences of foot health in patients with rheumatoid arthritis: a qualitative study. 2022 Jan PURPOSE: The aim of the study was to explore the experiences of foot health and the factors that hinder or facilitate foot health self-care in patients with RA. MATERIALS AND METHODS: A descriptive qualitative study design was used. Individual interviews were conducted with patients who had been diagnosed with RA (n = 20). The interview data were analysed using inductive content analysis. RESULTS: The participants highly valued their foot health. The factors that hindered their foot health included physical characteristics (such as the progression of RA), personal traits (such as lack of motivation), inequalities in access to professional foot care and problems with finding suitable shoes. The factors that facilitated their foot health included professional care, physical activity and practising foot self-care. CONCLUSIONS: Patients with RA value their foot health. It is important to identify the factors that hinder or facilitate this in order to support their rehabilitation and respond to their foot-health needs. Patients' foot health should be promoted, and equal access to professional foot care should be provided.Implications for rehabilitationActive foot self-care supported by professional health are facilitating factors for foot health.Maintaining and promoting physical activity is integral part of foot health.Regular assessments of foot health in patients with RA in addition to an evaluation of their footwear and education about caring for their own feet is needed.
32597556 MiR-1193 represses the proliferation and induces the apoptosis of interleukin-1β-treated 2020 Aug OBJECTIVES: To explore the roles of miR-1193/Janus kinase 3 (JAK3) axis and the potential mechanism in rheumatoid arthritis (RA). METHODS: The dysregulated genes and microRNAs (miRNAs) were screened using the datasets of GSE12021 and GSE72564, while the upstream miRNA of JAK3 was forecasted by TargetScan. Then the MH7A cells were treated with interleukin-1β (IL-1β) to induce local inflammation. Double luciferase report assay was used to estimate the association between JAK3 and miR-1193. Flow cytometry and 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays were taken to analyze the apoptosis and proliferation of MH7A cells with IL-1β-induced inflammation, respectively. The relative expression of genes and proteins were detected by quantitative real-time polymerase chain reaction and western blot analyses. Finally, rescue experiments were employed to explore the effects of miR-1193/JAK3 axis on IL-1β-induced inflammation. RESULTS: JAK3 was notably up-regulated in RA, and was targeted and negatively regulated by miR-1193 which was lowly expressed in RA tissues and IL-1β-treated cells. MiR-1193 mimic significantly inhibited while miR-1193 inhibitor promoted the proliferation of MH7A cells with IL-1β-induced inflammation. Furthermore, overexpression of JAK3 presented auxo-action while depletion of JAK3 exhibited inhibitory effect on the proliferation of MH7A cells with IL-1β-induced inflammation, which could be weakened by miR-1193 mimic and miR-1193 inhibitor, respectively. Analogously, JAK3 recovered the cell proliferation that inhibited by miR-1193 mimic and inhibited cell apoptosis enhanced by miR-1193 mimic. CONCLUSION: Up-regulation of miR-1193 suppressed the proliferation and expedited the apoptosis of MH7A cells with IL-1β-induced inflammation through targeting JAK3, which might provide novel understanding on the mechanism underlying RA.
32131874 The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through 2020 Mar 4 BACKGROUND AND AIM: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. METHODS: We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). RESULTS: Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3. CONCLUSIONS: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.
32494830 [Hand and foot injuries in rheumatoid patients : Tips and tricks in operative and conserva 2020 Aug Since the introduction of biologicals and small molecules for the treatment of inflammatory rheumatic diseases, these patients are more active and therefore sustain more accidents. The hands and feet are most affected by inflammatory rheumatic diseases, especially rheumatoid arthritis, and are also very exposed to injuries. Therefore, rheumatoid patients have a high coincidence of injuries and rheumatic destruction of the hands and feet. For this reason, trauma surgeons should nowadays have a basic knowledge of rheumatoid diseases including immunosuppressive medication as well as the specific conservative and operative treatment of rheumatic hand and foot deformities. This is necessary to avoid fundamental errors in the treatment of fractures and optimally used anesthesia for the benefit of the patient. The close cooperation between trauma surgeons and orthopedic rheumatologists is urgently recommended in the treatment of these injuries. Whenever possible, the treatment should be carried out conservatively because surgical treatment has a higher risk compared to the normal population due to the immunosuppressive treatment.
32890968 Pentraxin 3 inhibits fibroblast growth factor 2 induced osteoclastogenesis in rheumatoid a 2020 Nov BACKGROUND: Synovial fibroblasts (SFs) act as key effector cells mediating synovial inflammation and joint destruction in rheumatoid arthritis (RA). Fibroblast growth factor 2 (FGF2) and its receptors (FGFRs) play important roles in RASF-mediated osteoclastogenesis. Pentraxin 3 (PTX3) is a soluble pattern recognition receptor with nonredundant roles in inflammation and innate immunity. PTX3 is produced by various cell types, including SFs and is highly expressed in RA. However, the role of PTX3 in FGF2-induced osteoclastogenesis in RA and the underlying mechanism have been poorly elucidated. METHODS: We first determined the expression of FGF2 and RANKL in synovial tissue and synovial fluid of RA patients. We then examined the effect of PTX3 on RASF osteoclastogenesis induced by endogenous and exogenous FGF2 in isolated RASF cells treated with FGF2 and/or recombinant PTX3 (rPTX3). Thirdly, we analyzed the effect of PTX3 on FGF2 binding to FGFR-1 and HSPG receptors on RASFs. Lastly, we evaluated joint morphology after injection of rPTX3 into collagen-induced arthritis (CIA) mice. RESULTS: FGF2 was confirmed to be highly expressed in both synovial tissue and synovial fluid of RA patients. FGF2 promoted cell proliferation and increased the expressions of RANKL and ICAM-1 and RANKL/OPG to induce osteoclastogenesis in RASF, while anti-FGF2 neutralized this effect. PTX3 significantly inhibited FGF2-induced RASF cell growth and osteoclastogenesis by preventing the interaction of (125)I-FGF2 and FGFRs on the same cells. In addition, administration of rPTX3 significantly ameliorated cartilage and bone destruction in mice with CIA. CONCLUSIONS: PTX3 exhibited an inhibitory effect on the autocrine and paracrine stimulation of FGF2 on SFs, and ameliorated bone destruction in CIA mice. PTX3 may be implicated in bone destruction in RA, which may provide theoretical evidence and potential therapeutic targets for RA treatment.
30900933 Vaccination against autoimmune diseases moves closer to the clinic. 2020 Biologicals, e.g. TNF inhibitors, have improved dramatically the efficacy of medical interventions in autoimmune diseases, such as in rheumatoid arthritis (RA). However, although progressive inflammation can be halted in this way, no drug-free remissions or lasting cures are reached. For this to become real, therapies based on induction antigen-specific immune tolerance are sought. This review describes mechanisms of tolerance and the current possibilities for induction of therapeutic tolerance through antigen-specific vaccination approaches. And despite the fact that for various diseases the search for appropriate autoantigens is ongoing, pioneering studies are now already developed that use more broadly inflammation associated antigens. Through their capacity to preferentially induce regulatory T cells, heat shock proteins are an attractive source of such broadly inflammation associated antigens.