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ID PMID Title PublicationDate abstract
31309643 A randomized, triple-blind, placebo-controlled clinical trial, evaluating the sesamin supp 2019 Sep Inflammation is one of the main characteristics of rheumatoid arthritis. Based on the antiinflammatory properties of sesame, this study was conducted to evaluate the sesamin supplement effects on serum levels of some proteolytic enzymes, inflammatory biomarkers, and clinical indices in women with rheumatoid arthritis. In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients were randomly divided in intervention and control groups. Patients received 200-mg/day sesamin supplement or placebo in the intervention and control group for 6 weeks. Serum levels of proteolytic enzymes (hyaluronidase, aggrecanase, and matrix metalloproteinases-3) and inflammatory biomarkers (hs-CRP, IL-1β, IL-6, TNF-α, and cyclooxygenase-2) were measured with enzyme-linked immunosorbent assay method at the beginning and end of the study. After intervention, serum levels of hyaluronidase and matrix metalloproteinases-3 decreased significantly in sesamin group. Also, serum levels of hs-CRP, TNF-α, and cyclooxygenase-2 in intervention group were significantly decreased in intervention group compared with placebo group. Sesamin supplementation also caused a significant reduction in the number of tender joints and severity of pain in these patients. According to the results, it seems that the sesamin by reducing inflammatory mediators can relieve clinical symptoms and pathological changes that caused by inflammatory impairment in patients with rheumatoid arthritis.
30536918 Biological links in periodontitis and rheumatoid arthritis: Discovery via text-mining PubM 2019 Aug BACKGROUND AND OBJECTIVE: Primary research concerning molecular pathways that link rheumatoid arthritis with periodontitis is limited. Biomedical literature data mining can offer insights into putative linkage mechanisms toward hypothesis development, based on information discovery. The aim of this study was to explore potential Periodontitis-Rheumatoid Arthritis biological links by analysing "overlapping" genes reported in biomedical abstracts. MATERIAL AND METHODS: PubMed abstracts for terms: (a) "Periodontitis" or "Periodontal Diseases" (PD), (b) "Rheumatoid arthritis" (RA), and (c) their combination with "AND" (RA+PD), were each text-mined to extract genes using "Human Genome Nomenclature Committee" (HGNC) symbols. A gene-set common to RA and PD abstracts was determined (RA∩PD). Gene ontology (GO) profiles of RA∩PD and RA+PD were compared using "GoProfiler." Minimum order protein-protein interaction (PPI) and gene-miRNA networks of "differential genes" between RA∩PD and RA+PD were constructed with "networkAnalyst." RESULTS: Among 1676 genes documented in RA (10 5241 abstracts), and 893 genes in PD (80 982 abstracts), 535 genes were common (RA∩PD), from which 35 genes were also documented in RA+PD (415 abstracts). 41 GO-terms significantly different between RA∩PD and RA+PD GO profiles represented 38 biological processes including; nitric oxide metabolism, immunoglobulin production, hormonal regulation, catabolic process down-regulation, and leukocyte proliferation. The 500 differential genes' PPI and gene-miRNA networks showed REL, TRAF2, AQP1 genes, and miRNAs 335-5p, 17-5p, 93-5p with genes HMOX1 and SP1 as hub nodes. CONCLUSIONS: Text-mining biomedical abstracts revealed potentially shared but un-investigated links between PD and RA, meriting further research.
30718650 High percentages and activity of synovial fluid NK cells present in patients with advanced 2019 Feb 4 Rheumatoid Arthritis (RA) causes chronic inflammation of joints. The cytokines TNFα and IFNγ are central players in RA, however their source has not been fully elucidated. Natural Killer (NK) cells are best known for their role in elimination of viral-infected and transformed cells, and they secrete pro-inflammatory cytokines. NK cells are present in the synovial fluids (SFs) of RA patients and are considered to be important in bone destruction. However, the phenotype and function of NK cells in the SFs of patients with erosive deformative RA (DRA) versus non-deformative RA (NDRA) is poorly characterized. Here we characterize the NK cell populations present in the blood and SFs of DRA and NDRA patients. We demonstrate that a distinct population of activated synovial fluid NK (sfNK) cells constitutes a large proportion of immune cells found in the SFs of DRA patients. We discovered that although sfNK cells in both DRA and NDRA patients have similar phenotypes, they function differently. The DRA sfNK secrete more TNFα and IFNγ upon exposure to IL-2 and IL-15. Consequently, we suggest that sfNK cells may be a marker for more severely destructive RA disease.
30148440 Risk of hospitalisation for serious bacterial infections in patients with rheumatoid arthr 2019 Jan OBJECTIVES: The aims of this study were to define the risk of serious bacterial infections in patients receiving specific biological disease-modifying anti-rheumatic drugs (bDMARDs) and evaluating the effect of concomitant synthetic DMARDs (sDMARDs) in a large population-based sample of rheumatoid arthritis (RA) deriving from an administrative health database. METHODS: Data were extracted from health databases of Lombardy Region, Italy (2004-2013), as a part of the RECord-linkage On Rheumatic Diseases (RECORD) study. Patients with RA treated with approved bDMARDs were included. Hospitalisations for bacterial infections were evaluated by hospital discharge forms. The association between drug exposure and infections was assessed by survival models, with time-dependent covariates. Results are presented as hazard ratios (HR) and 95%CI, crude and adjusted for pre-specified confounders (sex, age, disease duration, Charlson Comorbidity Index, previous biologics, previous infections, use of methotrexate, leflunomide, corticosteroids, non-steroidal anti-inflammatory drugs). RESULTS: 4,656 RA patients with at least one bDMARD prescription were included, for a total of 7,601 biological courses; 3,603 (77.4%) women with a mean (SD) age of 55.8 (12.7) years. Crude incidence rate of hospitalised infection ranged from 0.14 to 2.95 per 1000 person-years. After multivariable adjustment, abatacept users (HR 0.29, 95%CI 0.10-0.82) had significantly lower risk of infections compared to etanercept. Concurrent treatment with methotrexate (0.72, 0.52-0.99) reduced the overall risk of infection while glucocorticoids increased it (1.09 per mg/day, 1.06-1.11). CONCLUSIONS: In RA patients treated with bDMARDs, abatacept was associated with the lowest risk of infections; overall risk was mitigated by concomitant methotrexate and increased by glucocorticoids in a dose-dependent manner.
30374749 Acceptable quality of life and low disease activity achievable among transition phase pati 2019 Mar OBJECTIVES: Across diagnosis groups, transition of adolescents and young adults from children's hospitals to adult care associates with decreased treatment adherence and suboptimal treatment results. Our aim was to compare the health-related quality of life (HRQoL) and disease activity of juvenile idiopathic arthritis (JIA) patients after the transfer of care to the adult clinic and adult patients in the same outpatient clinic. METHODS: All consecutive JIA patients aged 16 to 20 years who visited the transition clinic between September 2016 and August 2017 and all consecutive adult onset arthritis patients between December 2016 and August 2017 in the rheumatology outpatient clinic of Helsinki University Hospital were evaluated. HRQoL was measured by a generic instrument, 15D. RESULTS: A total of 291 patients, 130 JIA, and 161 adults were identified with respective median disease durations of 6.5 and 4.0 years. Adults had lower HRQoL measured by 15D (median 0.90 vs. 0.96, P < 0.001) and higher Disease Activity Score 28 (DAS28) than JIA patients (median 2.4 vs. 1.6, P < 0.001). Adults smoked more frequently than JIA patients (22% vs. 7%, P < 0.001). In multiple regression, female gender, smoking, disease activity, and obesity were associated with poorer HRQoL. Smoking adults had more active disease (DAS28 median 3.1 vs. 2.1, P = 0.031) and lower HRQoL (15D median 0.86 vs. 0.93, P < 0.001) than non-smoking adults. CONCLUSIONS: Transition phase JIA patients had acceptable HRQoL and lower disease activity than patients with adult onset rheumatic diseases with similar disease duration. Smoking was associated with more active disease and lower HRQoL.
30685961 Simplified disease activity changes in real-world practice: a nationwide observational stu 2020 Jan BACKGROUND/AIMS: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice. METHODS: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed. RESULTS: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. CONCLUSION: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.
31901568 Deciphering the chemical profile and pharmacological mechanisms of Baihu-Guizhi decoction 2020 Feb BACKGROUND: Baihu-Guizhi decoction (BHGZD) has been extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic effect. However, the material basis and the underlying mechanisms of BHGZD against RA have not been fully elucidated. PURPOSE: To investigate the chemical profile and the pharmacological mechanisms of BHGZD against RA. METHODS: The chemical constituents containing in BHGZD were identified using UFLC-Q-TOF-MS/MS system, and the corresponding putative targets were predicted. Then, the differentially expressed genes (DEGs) between adjuvant-induced arthritis (AIA) and normal control groups were identified using microarray analysis. After constructing the interaction network of "RA-related gene-BHGZD putative target", BHGZD candidate targets against RA were screened by topological analysis and further experimentally validated based on AIA rat model. RESULTS: A total of 41 chemical constituents were identified in the water extract of BHGZD, which were predicted to hit 1312 putative targets. Additionally, 26 DEGs between the AIA and normal control groups were defined as "RA-related genes", which were functionally involved into the imbalance of "inflammation-immune" system during RA progression. On the basis of the topological importance in the network of "RA-related gene-BHGZD putative target", 177 BHGZD candidate targets against RA were identified. Among them, TLR4, c-Fos/AP-1, IL2 and TNF had direct interactions with each other and also function as crucial components of toll-like receptor and T cell receptor signaling pathways, which may play important roles in maintaining the balance of "inflammation-immune" system. Experimentally, we verified that BHGZD dose-dependently attenuated the severity, pathological changes, as well as mechanical, cold, and heat hypersensitivities during RA progression based on the AIA rat model. Further western blot analysis demonstrated that BHGZD significantly reduced the protein levels of TLR4, c-Fos/AP-1, IL2 and TNF, which were induced by RA modeling, in the inflamed joints of AIA rats (all p<0.05). CONCLUSION: This study combining the chemical and transcriptomic profilings, target prediction, network calculation and experimental validations identifies the chemical constituents containing in BHGZD and offers the convincing evidence that BHGZD may ameliorate RA partially by restoring the balance of "inflammation-immune" system and subsequently reversing the pathological events during RA progression through regulating the TLR4-c-Fos-IL2-TNF axis.
32186105 Total glucosides of paeony improve complete freund's adjuvant-induced rheumatoid arthritis 2019 Aug OBJECTIVE: To investigate the mechanism underlying anti-inflammatory and immunoregulatory effect of total glucosides of paeony (TGP) based on toll-like receptor 2 (TLR2) mediated tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6)/nuclear factor-kappa B (NF-κB) pathway activation in rats with rheumatoid arthritis. METHODS: Adjuvant arthritis (AA) model was developed by complete freund's adjuvant (CFA) immunization. TGP (100, 50, 25 mg/kg) and celecoxib (2.8 mg/kg) were administered by intragastric administration for 21 d. Right hind paw swelling was assessed every 2 d. After 21 d, synovial changes of the ankle were detected by histopathology. CD4+ and CD8+ T cell amounts in peripheral blood were measured by flow-cytometrically. Gene and protein levels of toll-like receptor (TLR)2, TRAF6, tumor necrosis factor ligand superfamily member 6 (FASLG) in the spleen were assessed by RT-qPCR and Western Bolt, respectively. Nuclear expression of NF-κB p65 was detected by NF-κB p65 Assay Kit. RESULTS: Paw swelling and synovium lesions were obviously aggravated in AA rats. These symptoms were significantly relieved by TGP. The ratio of CD4+/CD8+ T cell was increased in AA rats, while TGP reduced this increased ratio. Gene and protein levels of splenic TLR2, TFAR6 and FASLG, and nuclear NF-κB p65 in AA rats were significantly increased, but overtly inhibited by TGP. CONCLUSION: These findings suggest that TGP's anti-inflammatory effect onRA in rats with CFA may be related to the downregulation of TLR2/TRAF6/NF-κB pathway and the regulation of T cell subsets.
33086970 Bow hunter's syndrome after cervical laminoplasty in a patient with rheumatoid arthritis w 2020 Jan Bow hunter's syndrome, or rotational vertebral artery (VA) occlusion, refers to vertebrobasilar insufficiency due to mechanical occlusion of the VA. We present a case of surgical treatment for bow hunter's syndrome that occurred after cervical laminoplasty in a patient with rheumatoid arthritis with bony ankylosis of the facet joints. A 59-year-old female with rheumatoid arthritis experienced sudden incomplete left hemiplegia. Fifteen months earlier, the patient had undergone cervical decompression surgery between C3 and C7. MRI of the head showed cerebral infarction in the right VA area, while vertebral angiography with the head rotated to the right revealed that the right VA was occluded at the level of C3-C4. The patient was successfully treated via posterior cervical fusion from C2 to C7. Patients with rheumatoid arthritis have a potential risk of cervical bony ankyloses. Cervical laminoplasty for patients with cervical bony ankyloses can induce rotational VA occlusion due to spinal rotational instability.
30652645 Reinterpreting Evidence of Rheumatoid Arthritis-Associated Interstitial Lung Disease to Un 2019 Interstitial Lung Disease (ILD) is a well-known complication of rheumatoid arthritis (RA) which often results in significant morbidity and mortality. It is often diagnosed late in the disease process via descriptive criteria. Multiple subtypes of RA-ILD exist as defined by chest CT and histopathology. In the absence of formal natural history studies and definitive diagnostics, a conventional dogma has emerged that there are two major subtypes of RA-ILD (nonspecific interstitial pneumonia (NSIP) and Usual Interstitial Pneumonia (UIP)). These subtypes are based on clinical experience and correlation studies. However, recent animal model data are incongruous with established paradigms of RA-ILD and beg reassessment of the clinical evidence in order to better understand etiology, pathogenesis, prognosis, and response to therapy. To this end, here we: 1) review the literature on epidemiology, radiology, histopathology and clinical outcomes of the various RAILD subtypes, existing animal models, and current theories on RA-ILD pathogenesis; 2) highlight the major gaps in our knowledge; and 3) propose future research to test an emerging theory of RAILD that posits initial rheumatic lung inflammation in the form of NSIP-like pathology transforms mesenchymal cells to derive chimeric disease, and subsequently develops into frank UIP-like fibrosis in some RA patients. Elucidation of the pathogenesis of RA-ILD is critical for the development of effective interventions for RA-ILD.
31337345 An overlap of Alport syndrome and rheumatoid arthritis in a patient and literature review. 2019 Jul 23 BACKGROUND: Alport syndrome is a rare genetic kidney disease, and rheumatoid arthritis as a common autoimmune disease also causes renal lesions in addition to arthritis. The overlap of them has rarely been reported. CASE PRESENTATION: A 44-year-old man had a history of multi-joint swelling and pain for more than half a year. His laboratory data with double positive for rheumatoid factor and anticitrullinated protein antibodies further supported the diagnosis of early rheumatoid arthritis. His previous medical history including progressive hearing loss for several years and microhematuria for one year attracted our attention. Renal biopsy showed thin basement membrane nephropathy and lymphocytes infiltration of interstitium. To make a precise diagnosis, targeted Next Generation Sequencing (NGS) of an inherited renal disease panel including Alport syndrome genes was performed, which revealed the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Further in silico analyses predicted that the p. Cys451Arg mutation is functionally "damaging", so the diagnosis of Alport syndrome was finally proved. The patient has been receiving the treatment of total glucosides of paeony and leflunomide for rheumatoid arthritis, and Cozaar 50 mg for the protection of kidney so far. During the 10-months follow-up, swelling and tenderness of the joints in this patient had been generally relieved, with no obvious improvement in microhematuria and a slight increase in proteinuria. CONCLUSION: we reported an adult man with the coexistence of rheumatoid arthritis and Alport syndrome with the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Whether the overlap of them is occasional or has a common pathophysiological mechanism is still unclear.
30295427 Effect of Physical State on Pain Mediated Through Emotional Health in Rheumatoid Arthritis 2019 Sep OBJECTIVE: Pain is one of the main symptoms of patients with rheumatoid arthritis (RA). Pain in RA is caused by specific physical changes, such as joint destruction, and is therefore used as a disease activity marker. Although pain can also be influenced by emotional factors, neither the effect of emotional health nor the indirect effect of the physical state mediated by emotional health on pain has been quantified. METHODS: A total of 548 patients with RA participated. Emotional health was assessed using the Hospital Anxiety and Depression Scale (HADS). Measures routinely used in practice were used to evaluate the physical state and pain. To quantify the effects of the physical state on emotional health, and the effects of both physical and emotional health on pain, we used structural equation modeling, with emotional health, physical state, and pain as latent variables. RESULTS: The prevalence of anxiety and depression (HADS score ≥8 for each) among patients with RA was 18.7% and 29.4%, respectively. Emotional health was significantly influenced by the physical state (β = 0.21). Pain was affected by physical (β = 0.54) and emotional health (β = 0.29). The effect of the physical state on pain was mediated by emotional health, with this mediation effect (β = 0.06) accounting for 10.2% of the total effect. CONCLUSION: The magnitude of pain in RA is determined by the mediation effect of emotional health as well as the direct physical state. Our findings suggest that emotional factors should be taken into account when assessing RA disease activity.
31523787 Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthrit 2020 Jan OBJECTIVES: CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA. METHODS: All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software. RESULTS: Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604-3.098; SMD = 1.801, 95% CI = 1.145-2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135-4.229; SMD = 0.767, 95% CI 0.503-1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias. CONCLUSIONS: This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA.Key Point• First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors.
31765451 The relationship between epicardial adipose tissue and arterial stiffness in patients with 2019 Nov 24 AIM: To evaluate the relationship between epicardial adipose tissue (EAT) and arterial stiffness (AS) in patients with rheumatoid arthritis (RA), considering cardiovascular risk factors and disease characteristics. MATERIAL AND METHODS: A total of 84 RA patients were included in this cross-sectional study. EAT and carotid intima-media thickness (cIMT) were measured ultrasonographically while aortic pulse wave velocity (aPWV), the main AS parameter, was determined using an oscillometric device. RESULTS: Mean duration of RA was 12±9.5 years and disease activity score was 4.3±1.4, as assessed by Disease Activity Score-28 using C-reactive protein (DAS-28 CRP). The correlation analysis displayed a significant positive correlation between cIMT, aPWV and EAT (r= 0.037, p<0.001; r= 0.338, p=0.002 and r= 0.317, p=0.003). When a cutoff value of aPWV ≥10 m/s was established, patients with increased aPWV had significantly higher body mass index (p=0.04), waist circumference (p=0.01), triglycerides (p=0.04), EAT (p<0.001), hypertension (p=0.03) and marginally C-reactive protein (CRP) (p=0.05). Multivariate regression analysis showed that hypertension (p=0.033), increased CRP (p=0.016) and EAT (p=0.005) are the only independent predictors for increased aPWV. CONCLUSIONS: Our study found that increased AS independently correlated with EAT in patients with RA. Although the evaluation of these two parameters awaits further evidence to be included in the risk algorithms for CVD prevention, their role in patients with inflammatory diseases may be even more significant than in the general population.
31306774 Effects of biological and targeted synthetic DMARDs on bone loss in rheumatoid arthritis. 2019 Sep Bone loss is a typical consequence of Rheumatoid Arthritis (RA). It occurs not only locally, affecting the inflamed joints (erosions), but also systemically, leading to osteopenia and/or overt osteoporosis, with increased risk of fragility fractures. This complication, often underestimated, can worsen the burden of disability in RA patients. Moreover, systemic and local bone loss are closely intertwined as osteoporosis per se can facilitate the development of erosions. A fundamental role in this process is played by the osteoimmunologic dysregulation typical of RA and other chronic inflammatory conditions. The poor response to the DMARDs, in terms of progression of bone erosions, might depend on the concomitant osteoporosis and on other determinants of bone loss. Thus, we need a deeper investigation in RA patients of bone health and effects of DMARDs on it and, eventually, a specific anti-osteoporotic treatment, other than DMARDs, for the prevention of both fragility fractures and bone erosions. The present review summarizes the most relevant evidence on systemic bone loss of biological and targeted synthetic DMARDs.
30159791 Determination of the minimally important difference (MID) in multi-biomarker disease activ 2019 Feb The Multi-Biomarker Disease Activity (MBDA) score is a validated rheumatoid arthritis (RA) disease activity measure based on 12 serum biomarkers. Here, we evaluate short-term biological variability of MBDA scores to determine the magnitude of change that might be considered clinically meaningful. Twenty-eight adult seropositive RA patients with clinically stable disease and no changes in RA medications for 4 weeks prior to study were enrolled. Nine serum samples were obtained over four consecutive days (non-fasting). MBDA score variation was assessed day-to-day (daily) and within 24 h (diurnal). The standard deviation (SD) of MBDA scores was calculated by a linear mixed model including random effects for patient, day, and time of day. The minimally important difference (MID) was calculated as [Formula: see text]. A subgroup analysis was performed for patients with active RA (moderate or high MBDA score). The SD of MBDA score change in the full cohort was 4.7 in a combined daily-diurnal variation analysis, which corresponds with an MID of 11. The SD of MBDA score change in the subset of patients with active RA (moderate/high MBDA scores) was 3.6. This corresponds with an MID of 8 units in patients with active RA for whom clinicians are most likely to need guidance with respect to therapeutic decisions. Changes in MBDA score ≥ 8 represent a change in RA disease activity that clinicians can use as a benchmark for therapeutic drug efficacy and can be incorporated into a treat-to-target strategy.
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.
31293577 Distal Consequences of Oral Inflammation. 2019 Periodontitis is an incredibly prevalent chronic inflammatory disease, which results in the destruction of tooth supporting structures. However, in addition to causing tooth and alveolar bone loss, this oral inflammatory disease has been shown to contribute to disease states and inflammatory pathology at sites distant from the oral cavity. Epidemiological and experimental studies have linked periodontitis to the development and/or exacerbation of a plethora of other chronic diseases ranging from rheumatoid arthritis to Alzheimer's disease. Such studies highlight how the inflammatory status of the oral cavity can have a profound impact on systemic health. In this review we discuss the disease states impacted by periodontitis and explore potential mechanisms whereby oral inflammation could promote loss of homeostasis at distant sites.
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.
30785275 Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflam 2019 Mar 13 Among the various treatments, induction of synoviocyte apoptosis by natural products during a rheumatoid arthritis (RA) pathological condition can be considered to have vast potential. However, it is unclear that liquiritin, a kind of natural flavonoid extracted from the roots of Glycyrrhiza uralensis, induced the apoptosis of the synovial membrane and its molecular mechanism. In this study, interleukin-1β (IL-1β)-RA-FLS cells were incubated with different concentrations of liquiritin. An MTT assay, Hoechst 33342 staining, JC-1 staining, and Western blot were used to check the viability, cell apoptosis, mitochondrial membrane potential changes, and the expression of related proteins, respectively. In vivo, a TUNEL assay and HE staining of tissue were used for histopathological evaluation. Our results showed that liquiritin significantly inhibited the proliferation of IL-1β-induced-RA-FLS, promoted nuclear DNA fragmentation, and changed the mitochondrial membrane potential to accelerate cell apoptosis. Liquiritin downregulated the ratio of Bcl-2/Bax and inhibited the VEGF expression and phosphorylation of JNK and P38. Moreover, liquiritin improved the clinical score of rheumatism, inflammatory infiltration, and angiogenesis and induced apoptosis of the synovial tissue in vivo. Hence, liquiritin ameliorates RA by reducing inflammation, blocking MAPK signaling, and restraining angiogenesis.