Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
31428085 Shared and Unique Patterns of DNA Methylation in Systemic Lupus Erythematosus and Primary 2019 Objectives: To perform a cross-comparative analysis of DNA methylation in patients with systemic lupus erythematosus (SLE), patients with primary Sjögren's syndrome (pSS), and healthy controls addressing the question of epigenetic sharing and aiming to detect disease-specific alterations. Methods: DNA extracted from peripheral blood from 347 cases with SLE, 100 cases with pSS, and 400 healthy controls were analyzed on the Human Methylation 450k array, targeting 485,000 CpG sites across the genome. A linear regression model including age, sex, and blood cell type distribution as covariates was fitted, and association p-values were Bonferroni corrected. A random forest machine learning classifier was designed for prediction of disease status based on DNA methylation data. Results: We established a combined set of 4,945 shared differentially methylated CpG sites (DMCs) in SLE and pSS compared to controls. In pSS, hypomethylation at type I interferon induced genes was mainly driven by patients who were positive for Ro/SSA and/or La/SSB autoantibodies. Analysis of differential methylation between SLE and pSS identified 2,244 DMCs with a majority of sites showing decreased methylation in SLE compared to pSS. The random forest classifier demonstrated good performance in discerning between disease status with an area under the curve (AUC) between 0.83 and 0.96. Conclusions: The majority of differential DNA methylation is shared between SLE and pSS, however, important quantitative differences exist. Our data highlight neutrophil dysregulation as a shared mechanism, emphasizing the role of neutrophils in the pathogenesis of systemic autoimmune diseases. The current study provides evidence for genes and molecular pathways driving common and disease-specific pathogenic mechanisms.
31218368 Hydroxychloroquine was associated with reduced risk of new-onset diabetes mellitus in pati 2019 Oct 1 OBJECTIVES: To determine whether taking hydroxychloroquine (HCQ) could prevent the development of new-onset diabetes mellitus (DM) among patients with Sjögren syndrome (SS). METHODS: This is a nationwide, population-based, retrospective cohort study utilizing the Taiwan National Health Insurance Research Database (NHIRD). Data were collected from 1 January 1999, through 31 December 2013, using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. In total, 7774 patients newly diagnosed with SS by at least three outpatient visits or one inpatient admission were selected from the NHIRD as participants. Patients who had previously been diagnosed with DM and whose follow-up durations shorter than 90 days were excluded. HCQ exposure group includes patients who had been diagnosed with SS no longer than 180 days previously, and had been prescribed HCQ for the first time for at least 90 days. The diagnosis of DM was defined as at least two outpatient visits or one inpatient admission with anti-diabetic medication prescription. RESULTS: Patients with SS treated with HCQ had a significantly lower cumulative incidence of new-onset DM than those not treated with HCQ (adjusted hazard ratio: 0.51, 95% confidence interval: 0.28-0.96, P < 0.05). HCQ use for 3 years or more had favorable protective effects (adjusted hazard ratio: 0.22, CI: 0.05-0.92). CONCLUSIONS: HCQ reduced the incidence of DM in a time and dose-dependent manner. Patients with SS who had taken HCQ for 3 years or more exhibited significant protective effects against developing new-onset DM.
30766890 Clinical Correlations of Novel Autoantibodies in Patients with Dry Eye. 2019 BACKGROUND: Diagnostic criteria for Sjögren's syndrome (SS) are continually being updated in pursuit of more precise and earlier diagnosis to prevent its complications. Owing to the high rate of false negative traditional serological markers, the need for better serological testing remains. OBJECTIVE: To investigate the clinical significance of three recently discovered novel autoantibodies, anti-salivary gland protein 1 (SP1), anti-carbonic anhydrase 6 (CA6), and anti-parotid secretory protein (PSP), in a cohort of dry eye patients with suspected underlying inflammatory/autoimmune disease. METHODS: Medical records of 136 patients with a primary diagnosis of dry eye who underwent laboratory testing between April 2014 and July 2017 were reviewed retrospectively. Data regarding demographic information, ocular and systemic symptoms, previous medical diagnoses, serological test results, and minor salivary gland biopsy results were collected. Dry eye evaluations included tear osmolarity, Schirmer test without anesthesia, conjunctival lissamine green staining, and corneal fluorescein staining in the order listed here. RESULTS: Of the 136 patients, 9 (9/136, 6.6%) presented with a history of SS, and 9 additional patients (9/127, 7%) received a new diagnosis of SS as a result of evaluations. Fifty-six patients (56/136, 41%) tested positive for at least one of the novel autoantibodies. Fifty-four percent (6/11) of patients with primary SS who underwent the novel serological testing had a positive anti-PSP. Of those, 2 (2/11, 18%) had negative traditional serology and had to undergo minor salivary gland biopsy for definitive diagnosis. Anti-CA6 was associated with increased corneal and conjunctival staining after adjusting for age, sex, and other serologic markers (HR = 1.5, 95% CI = 1.20-1.97, and p = 0.009 and HR = 1.4, 95% CI = 1.04-1.76, and p = 0.02, respectively). CONCLUSIONS: This cross-sectional study demonstrated that anti-CA6 is seen in patients with severe aqueous-deficient dry eye. Whether these patients have an early stage of SS or a different type of autoimmune condition may be determined through longitudinal studies.
31322605 [Oral health in patients with systemic sclerosis]. 2019 The aim of this study was to conduct literature review about oral manifestations of scleroderma. Systemic sclerosis is a multisystem autoimmune disorder characterized by widespread fibrosis, vascular alterations and inflammation. Systemic sclerosis mainly affects people in age from 30 to 50 years, but the onset of disease can occur in any age. The disturbance of microcirculation with the activation and proliferation of endothelium and smooth muscle cells plays an important role in pathogenesis of sclerodrma. These changes lead to sclerosis and fibrosis of various part in human body. Orofacial manifestations of scleroderma include: reduced mouth opening, widening of periodontal ligament, teleangiectasia, bone lesions. Systemic scleroderma is often accompanied by Sjogren's syndrome. Oral manifestations of Sjogren's syndrome are recurrent parotitis, angular cheilitis, xerostomia and multiple caries. Sjogren's syndrome leads to negative impact on patients health and mental status. Orofacial manifestations of systemic sclerosis are still poorly known, that is why more researches should be made to improve dental treatment of patients with systemic sclerosis.
31270039 [rhPDCD5 suppresses pro-inflammatory cytokine secretion and proliferation and induces apop 2019 Jun 30 OBJECTIVE: To investigate the effect of recombinant human PDCD5 (rhPDCD5) treatment in a rat model of bovine II collagen (CII)-induced arthritis (CIA) on inflammatory cytokine secretion, proliferation and apoptosis of activated lymphocytes and explore the mechanisms of rhPDCD5-induced immunosuppression on activated lymphocytes. METHODS: Female Wistar rats were randomly divided into normal control group, CIA+ ovalbumin (OVA) group, CIA+ rhTNFR: Fc group, and CIA+rhPDCD5 group. The rats in the latter 3 groups received intraperitoneal injections of OVA (14 mg/kg), rhTNFR: Fc (3.5 mg/kg) or rhPDCD5 (14 mg/kg) from day 2 to day 26 following CII injection. On day 28, the spleens of the rats were harvested for preparing single cell suspensions of splenocytes, which were activated by CII (20μg/mL) or anti-CD3 (1μg/mL)+ anti-CD28 (2μg/mL) for 48 h and 72 h. The production of interferon-γ(IFN-γ) and interleukin-17A (IL-17A) by the activated lymphocytes was determined by ELISA of the culture supernatants. The proliferation and apoptosis of the activated lymphocytes were assessed using [(3)H]-thymidine incorporation assay and flow cytometry, respectively. RESULTS: Compared with those in CIA + OVA group, IFN-γand IL-17A secretions by the activated lymphocytes from rhPDCD5-treated CIA rats significantly decreased. RhPDCD5 treatment of the CIA rats obviously suppressed the proliferation and promoted apoptosis of the lymphocytes activated by CII or by anti-CD3 + anti-CD28. CONCLUSION: rhPDCD5 reduces pro-inflammatory cytokine secretion, inhibits the proliferation and promotes activation-induced cell death of activated CD4 (+) lymphocytes to produce immunosuppression in rat models of CIA.
31209415 [Role of erythroblast-like Ter cells in the pathogenesis of collagen-induced arthritis]. 2019 Jun 18 OBJECTIVE: To explore the role of Ter cells in the development of the collagen-induced arthritis (CIA), we detected their quantity changes in the spleen of different stages of CIA mice and analyzed the correlation between Ter cells and the joint scores, and we also analyzed the correlation between Ter cells and the frequencies of T and B cell subsets, so as to further understand the pathogenesis of rheumatoid arthritis. METHODS: The six to eight weeks DBA/1 mice were used to prepare CIA model. After the second immunization, we began to evaluate the joint score. According to the time of CIA onset and the joint score, the CIA mice were divided into three stages: early, peak and late stages. According to the final joint score, the CIA mice at the peak stage were subdivided into the high score group (score>8) and the low score group (score≤8). The frequencies of Ter cells in the spleen of the naïve mice and the CIA mice at various stages and the frequencies of T and B cell subsets in the spleen of the CIA mice at the peak stage were detected by flow cytometry, then we carried on the correlation analysis. RESULTS: The frequencies of Ter cells in the spleen of the CIA mice was significantly higher than those of the naïve mice (8.522%±2.645% vs. 1.937%±0.725%, P<0.01), the frequencies of Ter cells in the spleen of the high score group mice was significantly lower than those of the low score group (6.217%±0.841% vs. 10.827%±0.917%, P<0.01). The frequencies of Th1 cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.337%±0.110% vs. 0.727%±0.223%, P<0.05). The frequencies of Th17 cells in the spleen of the high score group mice was higher than those of the low score group mice (0.750%±0.171% vs. 0.477%±0.051%, P=0.099). The frequencies of germinal center B cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.243%±0.057% vs. 1.097%±0.015%, P<0.05). Correlation analysis results showed that the frequencies of Ter cells in the spleen of the CIA mice at the peak stage was strongly negatively correlated with the frequencies of CD4+ T, Th1, Th17, and germinal center B cells, and was strongly positively correlated with the frequencies of B10 cells, indicating that these cells might have a protective effect in CIA. Studies on dynamic changes showed that the frequencies of Ter cells in the spleen of the CIA mice at the late stage was significantly lower than those at the peak stage (0.917%±0.588% vs. 8.522%±2.645%, P<0.001), suggesting the protective effect of these cells in arthritis. CONCLUSION: Ter cells were significantly increased in the spleen of the CIA mice at peak stage, and were negatively correlated with joint scores and pathogenic immune cells, and positively correlated with protective immune cells. Ter cells were significantly decreased in the spleen of the CIA mice at the late stage. What we mentioned above suggests that Ter cells might be involved in the progression of rheumatoid arthritis as an immunomodulatory cell,but further in vivo and in vitro experiments are needed to verify its specific effects and mechanism.
31829244 Management of adult-onset Still's disease with interleukin-1 inhibitors: evidence- and con 2019 Dec 11 BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory condition characterized by fever, rash, and arthritis. Because of its rarity, clinical trials are inherently small and often uncontrolled. Our objective was to develop recommendations for the use of interleukin (IL)-1 inhibitors in the management of patients with AOSD, based on the best evidence and expert opinion. METHODS: A panel of 10 experts (9 rheumatologists and 1 pediatrician) was established. The first step was dedicated to a comprehensive literature review and development of statements. Two separate literature searches were performed on the MEDLINE (Pubmed), EMBASE, and BIOSIS databases through April 2018 to identify (1) differences and similarities between AOSD and pediatric Still's disease (systemic juvenile idiopathic arthritis [SJIA]) and (2) the efficacy and safety of IL-1 inhibitors in AOSD treatment. In the second step, the statements were submitted in a Delphi process to a panel of 67 rheumatologists. Consensus threshold was set at 66%: positive, > 66% of voters selected scores 3 to 5; negative, > 66% of voters selected scores 1 or 2. In the third step, the voting results were analyzed, and the statements were finalized. RESULTS: Eleven statements were developed. Forty-six of 67 rheumatologists (72%) participated in the Delphi process. A positive consensus was reached after the first round of voting and was full (> 95%) on the majority of statements. A large consensus was achieved in considering AOSD and SJIA as the same disease. The use of anti-IL-1 therapies in refractory patients was considered quite safe and effective both as the first and as a subsequent line of biologic treatment, especially in systemic patients. Because of the lack of head-to-head comparisons, a different profile of efficacy among IL-1 inhibitors could not be established. There was a large consensus that failure of the first IL-1 inhibitor does not preclude response to another one. The lack of studies comparing early versus late treatment did not allow to draw conclusions; however, data from SJIA suggest a better response in early treatment. CONCLUSIONS: The Delphi method was used to develop recommendations that we hope will help clinicians in the management of patients with AOSD refractory to conventional therapies.
31075042 Preliminary study on the application of deep learning system to diagnosis of Sjögren's sy 2019 Sep OBJECTIVES: This study estimated the diagnostic performance of a deep learning system for detection of Sjögren's syndrome (SjS) on CT, and compared it with the performance of radiologists. METHODS: CT images were assessed from 25 patients confirmed to have SjS based on the both Japanese criteria and American-European Consensus Group criteria and 25 control subjects with no parotid gland abnormalities who were examined for other diseases. 10 CT slices were obtained for each patient. From among the total of 500 CT images, 400 images (200 from 20 SjS patients and 200 from 20 control subjects) were employed as the training data set and 100 images (50 from 5 SjS patients and 50 from 5 control subjects) were used as the test data set. The performance of a deep learning system for diagnosing SjS from the CT images was compared with the diagnoses made by six radiologists (three experienced and three inexperienced radiologists). RESULTS: The accuracy, sensitivity, and specificity of the deep learning system were 96.0%, 100% and 92.0%, respectively. The corresponding values of experienced radiologists were 98.3%, 99.3% and 97.3% being equivalent to the deep learning, while those of inexperienced radiologists were 83.5%, 77.9% and 89.2%. The area under the curve of inexperienced radiologists were significantly different from those of the deep learning system and the experienced radiologists. CONCLUSIONS: The deep learning system showed a high diagnostic performance for SjS, suggesting that it could possibly be used for diagnostic support when interpreting CT images.
31684171 Methotrexate Restores CD73 Expression on Th1.17 in Rheumatoid Arthritis and Psoriatic Arth 2019 Nov 3 OBJECTIVES: Th1.17 are highly polyfunctional, potentially harmful CD4(+) effector T cells (Teff) through IFN-γ and IL-17A coproduction. Th1.17 take part in the pathophysiology of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which their hyper activation results in part from defects in negative regulation mechanisms. We recently demonstrated that the ecto-nucleotidase CD73 delineates a Th1.17-enriched Teff population and acts as an endogenous regulatory mechanism. Because Methotrexate (MTX), used as first line treatment of RA and PsA, increases extracellular concentrations of AMP and immunosuppressive adenosine, we investigated the modulation of CD73 by MTX treatment on Teff in RA/PsA patients. METHODS: In a prospective cohort of 26 RA and 15 PsA patients before or under MTX treatment, we evaluated CD73 expression on blood Teff subsets, their cytokine production and AMPase functions. RESULTS: We showed a decreased CD73 expression on Th1.17 and Th1 in untreated patients compared to healthy donors that was partly restored under MTX. This decrease in untreated patients leads to a halved Ado production by Th1.17 cells. CD73(+) Teff remained functional under MTX treatment, but their CD73 re-expression may contribute to control their activation. CONCLUSION: Our study unveils uncovered mode of action of MTX on Teff subsets modulation and in the adenosine-dependent termination of inflammation in RA and PsA.
32164967 Meloxicam. 2020 Meloxicam, an oxicam derivative: 4-Hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2- benzothiazine-3-carboxamide 1,1-dioxide, is a nonsteroidal anti-inflammatory drug (NSAID). It is a selective inhibitor of cyclooxygenase-2 (COX-2). It is used in the management of rheumatoid arthritis, acute exacerbations of osteoarthritis, ankylosing spondylitis and juvenile idiopathic arthritis. It is given in a single oral dose of 7.5mg, increased if necessary to a maximum of 15mg daily (7.5mg in the elderly). It may also be given by rectal suppository in doses similar to those used orally. The reported side effects of meloxicam are similar to those of nonsteroidal anti-inflammatory drugs (NSAIDs), such as abdominal pain, anemia, and edema. There is also an increased risk of serious gastrointestinal (GI) adverse events, including ulceration and bleeding. This profile is prepared to discuss and explain physical characteristics, Proprietary and nonproprietary names of meloxicam. It also includes methods of preparation, thermal and spectral behavior, methods of analysis, pharmacokinetics, metabolism, excretion and pharmacology.
30793992 Proteomic analysis of synovial fluid: current and potential uses to improve clinical outco 2019 Apr Synovial fluid (SF) is in close proximity to tissues which are primarily altered during articular disease and has significant potential to better understand the underlying disease pathogeneses of articular pathologies and biomarker discovery. Although development of mass spectrometry-based methods has allowed faster and higher sensitivity techniques, interrogation of the SF proteome has been hindered by its large protein concentration dynamic range, impeding quantification of lower abundant proteins. Areas covered: Recent advances have developed methodologies to reduce the large protein concentration dynamic range of SF and subsequently allow deeper exploration of the SF proteome. This review concentrates on methods to overcome biofluid complexity, mass spectrometry proteomics methodologies, extracellular vesicles proteomics and the application of advances within the field in clinical disease, including osteoarthritis, rheumatoid arthritis, spondyloarthritis and juvenile arthritis. A narrative review was conducted with articles searched using PubMed, 1991-2018. Expert opinion: The SF proteomics field faces various challenges, including the requirement for rigorous and standardised methods of sample collection/storage, the sensitivity and specificity of proteomic assays, techniques to combat the large protein concentration dynamic range and comprehensive data analysis to reduce falsely identified markers. Additionally, there are challenges in developing multi 'omic' integration techniques, with computational integration enhancing analysis.
30562713 Caffeic acid and ellagic acid ameliorate adjuvant-induced arthritis in rats via targeting 2019 Feb Rheumatoid arthritis (RA) is a chronic inflammatory arthropathy that principally attacks the joints. The present study aimed to explore the potential anti-arthritic effects of caffeic acid and ellagic acid in adjuvant-induced arthritis, compared to celecoxib. The current study also explored the underlying molecular mechanisms e.g., pro-inflammatory signals including chitinase-3-like protein-1 (CHI3L1); a glycoprotein that correlates with RA joint destruction besides angiogenesis, oxidative stres and apoptosis. Interestingly, caffeic and ellagic acids attenuated the severity of arthritis with comparable efficacy to celecoxib. Both agents effectively mitigated paw edema and inflammatory cell infiltration and protected the joint tissues against pannus formation along with cartilage and bone destruction. Notably, they also lowered the paw expression of NF-κB and the downstream effector CHI3L1 and its synthesis inducer IL-1β. They also lowered the levels of the tissue remodeling factor MMP-9 and the angiogenic signal VEGF in rat paws. Both agents also suppressed serum oxidative stress via diminishing lipid peroxides and nitric oxide together with augmentation of reduced glutathione in arthritic animals. Regarding apoptosis, they attenuated paw caspase-3 levels, favoring cell survival. Together, these favorable findings may advocate the use of caffeic and ellagic acids as adjunct modalities for the management of RA to mitigate joint damage.
30728752 Inhibition of pSTAT1 by tofacitinib accounts for the early improvement of experimental chr 2019 BACKGROUND: In order to gain insight into the early effects drawn by JAK inhibitors on intra-joint JAK/STAT-dependent signaling, we sought synovial activation of STATs and their end-products, along with their modification with tofacitinib (TOFA), at flare-up in antigen induced arthritis (AIA). New Zealand rabbits were randomly assigned to four groups -healthy controls, AIA, TOFA-treated AIA, or TOFA-treated controls-. AIA was induced with 4 weekly intra-articular ovalbumin injections in sensitized animals. TOFA (10 mg·kg(- 1)·day(- 1)) was administered for the last 2 weeks. Animals were euthanized 24 h after the last injection. RESULTS: AIA animals showed high-grade synovitis, which was partially improved by TOFA. No effects of the treatment were found on serum C-reactive protein or on the synovial macrophage infiltration at this stage. Synovial MMP-1,-3 and -13 expression levels in treated AIA rabbits were found to drop to those of controls, while a downregulation of IL6, IFNγ and TNF was evident in treated versus untreated AIA rabbits. Concurrently, a reduction in pSTAT1 and SOCS1, but not in pSTAT3, SOCS3 or active NFκB-p65, was noted with TOFA. CONCLUSIONS: Studying the mechanism of action of immunomodulatory drugs represents a major challenge in vivo, since drug-dependent decreases in inflammation very likely mask direct effects on disease mechanisms. This study design allowed us to prevent any confounding effect resulting from reductions in the overall inflammatory status, hence assessing the true pharmacological actions of TOFA in a very severe synovitis. Our findings point to pSTAT1 and MMPs as early molecular readouts of response to this JAK inhibitor.
30564856 Susceptibility-weighted MR imaging to improve the specificity of erosion detection: a pros 2019 May OBJECTIVE: To evaluate the diagnostic potential of susceptibility-weighted imaging (SWI) for the detection of erosions of the hand, compared to T1-weighted (T1w) magnetic resonance imaging (MRI). Computed tomography (CT) was used as a reference standard. MATERIALS AND METHODS: We prospectively investigated 37 patients with suspected arthritic activity of the hand. All patients underwent T1w, SWI, and CT on the same day. Patients were randomized to MRI or CT first. CT, T1w, SWI, and T1w/SWI were scored for erosions according to OMERACT RAMRIS guidelines. Specificity, sensitivity, and diagnostic accuracy were separately calculated for T1w, SWI, and T1w/SWI on a per-patient and per-bone basis using CT as reference. The one-tailed McNemar test was performed to test the number of erosion-positive patients in T1w, SWI, and T1w/SWI for non-inferiority. Measured erosion sizes were compared using Pearson's test. RESULTS: CT was positive for erosions in 16 patients and 55 bones. SWI and T1w/SWI had superior diagnostic accuracy (91.2 and 93.8%) compared to T1w (87.8%) driven by a higher specificity (93.8 and 96.5%) compared to T1w (88.8%). On the patient level, SWI and T1w/SWI showed non-inferiority (p = 0.11 and p = 0.38) but not T1w alone (p < 0.0001). The lesion size on CT correlated better with SWI (Pearson's r = 0.92) compared to T1w (r = 0.69). CONCLUSIONS: Adding SWI to a standard MRI protocol has the potential to improve erosion detection in hands by increasing specificity. SWI depicts bony erosions more accurately compared to standard MRI techniques.
31832600 Disease activity flares and pain flares in an early rheumatoid arthritis inception cohort; 2019 BACKGROUND: RA flares are common and disabling. They are described in terms of worsening inflammation but pain and inflammation are often discordant. To inform treatment decisions, we investigated whether inflammatory and pain flares are discrete entities. METHODS: People from the Early RA Network (ERAN) cohort were assessed annually up to 11 years after presentation (n = 719, 3703 person-years of follow up). Flare events were defined in 2 different ways that were analysed in parallel; DAS28 or Pain Flares. DAS28 Flares satisfied OMERACT flare criteria of increases in DAS28 since the previous assessment (≥1.2 points if active RA or ≥ 0.6 points if inactive RA). A ≥ 4.8-point worsening of SF36-Bodily Pain score defined Pain Flares. The first documented episode of each of DAS28 and Pain Flare in each person was analysed. Subgroups within DAS28 and Pain Flares were determined using Latent Class Analysis. Clinical course was compared between flare subgroups. RESULTS: DAS28 (45%) and Pain Flares (52%) were each common but usually discordant, with 60% of participants in DAS28 Flare not concurrently in Pain Flare, and 64% of those in Pain Flare not concurrently in DAS28 Flare. Three discrete DAS28 Flare subgroups were identified. One was characterised by increases in tender/swollen joint counts (14.4%), a second by increases in symptoms (13.1%), and a third displayed lower flare severity (72.5%). Two discrete Pain Flare subgroups were identified. One occurred following low disease activity and symptoms (88.6%), and the other occurred on the background of ongoing active disease and pain (11.4%). Despite the observed differences between DAS28 and Pain Flares, each was associated with increased disability which persisted beyond the flare episode. CONCLUSION: Flares are both common and heterogeneous in people with RA. Furthermore our findings indicate that for some patients there is a discordance between inflammation and pain in flare events. This discrete flare subgroups might reflect different underlying inflammation and pain mechanisms. Treatments addressing different mechanisms might be required to reduce persistent disability after DAS28 and Pain Flares.
30409417 Regulatory B cells: New players in inflammatory and autoimmune rheumatic diseases. 2019 Jun OBJECTIVE: Regulatory B cells (Bregs) are a new subset of B cells with immunoregulatory functions, mainly through IL-10 production. Bregs suppress inflammatory Th1 and Th17 differentiation and induce Tregs suppressing autoimmune diseases. The aim of the study was to review the literature related to Bregs in autoimmune rheumatic diseases (ARDs). METHODS: A literature review of publications in PUBMED published in English was performed using the relevant combinations of terms. RESULTS: All relevant publications are discussed. Overall, recent studies in rheumatic diseases found Bregs to be decreased in ANCA-associated vasculitides (AAV) and in systemic sclerosis (SSc), particularly in SSc-associated lung fibrosis. In AAV Bregs levels are negatively correlated with autoantibody levels whereas in SSc this association is less clear but there is an inverse association with Th1 and Th17 cells. In rheumatoid arthritis (RA), Bregs were decreased, particularly in RA-associated lung fibrosis. In psoriatic arthritis IL-10 + Bregs are decreased and inversely associated with Th1 and Th17 cells. In systemic lupus erythematosus (SLE), the role of Bregs is unclear. In experimental diseases, when Bregs were expanded ex-vivo, they ameliorated established disease. CONCLUSION: Bregs appear to be a new player in the pathogenesis of ARDs, and may offer a new strategy for therapeutic intervention.
31354003 Pedunculoside attenuates pathological phenotypes of fibroblast-like synoviocytes and prote 2019 Sep Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA.
30952390 Maximizing Engagement in Mobile Health Studies: Lessons Learned and Future Directions. 2019 May The widespread availability of smartphones, tablets, and smartwatches has led to exponential growth in the number of mobile health (mHealth) studies conducted. Although promising, the key challenge of all apps (both for research and nonresearch) is the high attrition rate of participants and users. Numerous factors have been identified as potentially influencing engagement, and it is important that researchers consider these and how best to overcome them within their studies. This article discusses lessons learned from attempting to maximize engagement in 2 successful UK mHealth studies-Cloudy with a Chance of Pain and Quality of Life, Sleep and Rheumatoid Arthritis.
31926570 Periodontal Diseases and Age-Related Macular Degeneration: Is There a Link? A Review. 2019 BACKGROUND: Age-related macular degeneration (AMD) induces irreversible loss of vision in older people. The exact physiopathology remains unclear, but numerous studies highlight the role of inflammation and multiple risk factors. Recent data show an altered periodontal condition subject to AMD. Periodontal diseases lead to the destruction of tooth-supporting tissues, mainly caused by the periodontal infection inducing a chronic inflammation. Periodontal diseases are known to be associated with several extraoral diseases such as diabetes, polyarthritis (rheumatoid arthritis), cardiovascular disease, and preeclampsia. OBJECTIVES: To assess emerging evidence suggesting an association between periodontitis and AMD. METHODS: To support this review, we performed a literature search using PubMed, Cochrane, and Google Scholar databases, completed by manual searches in periodontology journals. We included only the original studies published before July 2017 reporting data on periodontal diseases and AMD. No restrictions were made on the language. RESULTS: Persons with AMD showed more periodontal diseases, fewer teeth, and more alveolar bone loss than those without AMD. Also, a significant association was observed between periodontal diseases and AMD, but only in the youngest individuals studied. CONCLUSION: According to the studies included in this review, periodontal disease may be a plausible risk factor for AMD and may have a potential role in the earlier stages of this eye disease. Further studies should be encouraged for better understanding of this potential new relationship.
31858279 Correction to: Special issue-before translational medicine: laboratory clinic relations lo 2019 Dec 19 The above-mentioned article has been published online on 7 November 2019 as part of topical collection 'Before Translational Medicine: Laboratory Clinic Relations'.