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ID PMID Title PublicationDate abstract
32163856 Dexmedetomidine inhibits the invasion, migration, and inflammation of rheumatoid arthritis 2020 Mar 9 Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by inflammatory synovitis, but its pathogenesis remains unclear. NLRC5 is a newly discovered member of the NLR family that is effective in regulating autoimmunity, inflammatory responses, and cell death processes. Dexmedetomidine (DEX) has been reported to have a variety of pharmacological effects, including anti-inflammatory and analgesic effects. However, the role of DEX in RA has not been explored. In adjuvant-induced arthritis (AA) rat models, DEX (10 μg/kg and 20 μg/kg) reduced the pathological score, the arthritis score, paw swelling volume, and the serum levels of IL-1β, IL-6, IL-17A, and TNF-α. Moreover, by using Western blot and real-time quantitative PCR (RT-qPCR), it was demonstrated that DEX can inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9 and P-P65 in the synovial tissue of AA rats. In human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), DEX (250 nM and 500 nM) was found to inhibit the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65 following stimulation with TNF-α. Moreover, DEX can inhibit the invasion and migration of RA-FLSs stimulated by TNF-α. Finally, the expression of NLRC5 in RA-FLSs and AA rat models was also reduced by DEX. After silencing NLRC5 in RA-FLSs, the expression of IL-1β, IL-6, MMP-3, MMP-9, and P-P65, as well as the invasion and migration of cells, were significantly reduced. These results indicate that DEX inhibits the invasion, migration, and inflammation of RA-FLSs by reducing the expression of NLRC5 and inhibiting the NF-κB activation.
32921827 Work instability and associated factors among patients with rheumatoid arthritis in Greate 2020 OBJECTIVES: Rheumatoid arthritis (RA) affects patients' capacity to work. The Rheumatoid Arthritis Work Instability Scale (RA-WIS) is a reliable method to measure work instability (WI) (1-3). We lack data on the relationship between RA and work instability among Polish patients. Our study aimed to assess WI and associated factors among patients with RA. MATERIAL AND METHODS: The authors conducted a multi-centre cross-sectional observational study. 315 patients from three rheumatology centres were enrolled and filled in questionnaires, including demographic and self-reported clinical data, RA-WIS, and the Health Assessment Questionnaire (HAQ). Swollen and tender joint counts (SJC, TJC) were assessed by the attending physician, and current erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. We excluded 41 patients due to an incorrectly filled in form and analysed questionnaires of 274 patients. DAS28 (Disease Activity Score in 28 joints) and DAS28-CRP were calculated. We performed statistical analysis with Statistica v. 13.3 using the Mann-Whitney U test, χ(2) test, and Spearman's correlation. RESULTS: 140 (51%) patients were currently employed and their characteristics were analysed. In univariable analysis we identified the following risk factors for high risk WI: moderate-to-high disease activity (DAS28 ≥ 3.2 - OR 2.29, 95% CI 1.06-4.96, p = 0.033; DAS28-CRP ≥ 3.2 - OR 2.34, 95% CI 1.04-5.27, p = 0.038), ESR ≥ 30 mm/h in women and ≥ 20 mm/h in men (OR 2.65, 95% CI 1.20-5.89, p = 0.010), CRP ≥ 1 mg/dl (OR 4.02, 95% CI 1.78-9.10, p < 0.001), HAQ-DI > 1.0 (OR 2.23, 95% CI 1.04-4.81, p = 0.037) and at least moderate pain on the visual analogue scale (VAS p ≥ 4.5 cm - OR 5.31, 95% CI 2.36-11.96, p < 0.001).Correlations were moderate between RA-WIS and VASp (RS = 0.59, p < 0.001) and HAQ-DI (RS = 0.52, p < 0.001) but weak with disease activity indices (DAS28 [RS = 0.31, p < 0.001]; DAS28-CRP [RS = 0.28, p < 0.001]). CONCLUSIONS: Pain and disability are the main factors strongly associated with work instability among patients with RA.
33044165 Leptomeningitis in rheumatoid arthritis. 2021 Jan In this case report, we describe the case of a patient given the presumptive diagnosis of rheumatoid leptomeningitis on the basis of clinical findings and clinical response to antirheumatic medications after other causes of meningitis were excluded. Numerous case reports describe rheumatoid meningitis; however, rheumatoid leptomeningitis, in the absence of pachymeningitis, is a rare phenomenon. As such, the literature about it is scant. This unique case provides an opportunity to further characterize the symptoms and radiological findings of leptomeningitis in a patient with rheumatoid arthritis.
33263165 Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of th 2021 Mar Although treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) has significantly improved clinical outcomes in patients with rheumatoid arthritis (RA), many patients do not have access to these treatments. As cost-effective alternatives to their reference products (RPs), biosimilars provide an opportunity to increase access to bDMARDs. The European Medicines Agency and the US Food and Drug Administration have detailed pathways for the approval of biosimilars based on establishing the similarity of the biosimilar to the RP in terms of structure and function, pharmacokinetics (PK), efficacy, safety, and immunogenicity. A number of biosimilars of adalimumab, infliximab, etanercept, and rituximab RPs have been approved in the United States and/or European Union. This article is focused on the seven adalimumab biosimilars. A review of the data for the biosimilars FKB327, ABP 501, BI 695501, GP2017, MSB11022, PF-06410293, and SB5 confirm that these products are highly similar to the adalimumab RP with regard to structure, physicochemical and biological properties, PK, safety, immunogenicity, and efficacy in the treatment of RA and other chronic immune-mediated, inflammatory conditions. Data from several switching studies showed no changes in efficacy, safety, trough serum drug concentration, or immunogenicity between the biosimilars and their RP.Trial registration: ClinicalTrials.gov identifiers: NCT02260791, NCT02405780, NCT01970475, NCT02137226, NCT02045979, NCT02744755, NCT02144714, NCT02167139, NCT03014947, NCT02114931, NCT02640612, NCT02167139, NCT03052322, NCT02480153. EudraCT numbers: 2012-005140-23, 2012-000785-37, 2013-003722-84, 2015-000579-28, 2014-002879-29, 2014-000662-21, 2013-004654-13, 2015-002634-41, 2014-005229-11, 2016-002852-26, 2014-000352-29.
33363467 Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis 2020 The activated Gα protein subunit (Gαs) and the inhibitory Gα protein subunit (Gαi) are involved in the signal transduction of G protein coupled receptors (GPCRs). Moreover, the conversion of Gαi/Gαs can couple with sphingosine-1-phosphate receptors (S1PRs) and have a critical role in rheumatoid arthritis (RA). Through binding to S1PRs, sphingosine-1-phosphate (S1P) leads to activation of the pro-inflammatory signaling in rheumatoid arthritis synovial fibroblasts (RASFs). Geniposide (GE) can alleviate RASFs dysfunctions to against RA. However, its underlying mechanism of action in RA has not been elucidated so far. This study aimed to investigate whether GE could regulate the biological functions of MH7A cells by inhibiting S1PR1/3 coupling Gαi/Gαs conversion. We use RASFs cell line, namely MH7A cells, which were obtained from the patient with RA and considered to be the main effector cells in RA. The cells were stimulated with S1P (5 μmol/L) and then were treated with or without different inhibitors: Gαi inhibitor pertussis toxin (0.1 μg/mL), S1PR1/3 inhibitor VPC 23019 (5 μmol/L), Gαs activator cholera toxin (1 μg/mL) and GE (25, 50, and 100 μmol/L) for 24 h. The results showed that GE may inhibit the abnormal proliferation, migration and invasion by inhibiting the S1P-S1PR1/3 signaling pathway and activating Gαs or inhibiting Gαi protein in MH7A cells. Additionally, GE could inhibit the release of inflammatory factors and suppress the expression of cAMP, which is the key factor of the conversion of Gαi and Gαs. GE could also restore the dynamic balance of Gαi and Gαs by suppressing S1PR1/3 and inhibiting Gαi/Gαs conversion, in a manner, we demonstrated that GE inhibited the activation of Gα downstream ERK protein as well. Taken together, our results indicated that down-regulation of S1PR1/3-Gαi/Gαs conversion may play a critical role in the effects of GE on RA and GE could be an effective therapeutic agent for RA.
32821181 Rheumatoid Arthritis Saudi Database (RASD): Disease Characteristics and Remission Rates in 2020 BACKGROUND: National Registries are essential to direct current practice. Rheumatoid arthritis (RA) registries in the middle east and North Africa remain scarcely represented. OBJECTIVE: To describe a population of Saudi RA patients and to compare the findings to internationally reported data. METHODS: This is an observational study that was conducted at Doctor Soliman Fakeeh Hospital (DSFH) in Saudi Arabia. The study ran from 2014 to 2018 using a pool of 433 patients. Inclusion criteria included adults older than 18 years of age who fulfilled the 2010 American College of Rheumatology criteria for the diagnosis of RA and who were also regular visitors in our rheumatology clinics. Data were collected directly from patients and entered in a specially designed program. RESULTS: At initial presentation, 45.5% had demonstrated active disease (moderate or high disease activity) based on DAS-28-CRP scores, while 54.5% were in low disease activity or remission. The remission rates after 1 year had increased to 79.6% (345 patients), while 9.7% (42 patients) and 10.6% (46 patients) had low disease activity and moderate disease activity, respectively. It was also found that the female gender, higher Health Assessment Questionnaire-Disability Index (HAQ-DI) and longer lag1/lag2 periods were associated with higher disease activity in our population. CONCLUSION: We detected higher remission rates at 1 year of follow-up. This could be attributed to many factors, including good referral systems with easier access to biologics. We aim to expand this registry to the national level.
33133404 Efficacy of Periarticular Cocktail Injection in Rheumatoid Patients Undergoing Total Knee 2020 Nov BACKGROUND: Pain control after total knee replacement (TKR) is of primary importance to joint replacement surgeons to achieve good functional outcome post-surgery. This becomes even more challenging when these major procedures are done in immunocompromised patients like rheumatoid arthritis. Good peri-operative analgesia facilitates early rehabilitation, improves patient satisfaction, and reduces the hospital stay. The adverse effects caused by epidural analgesia or parenteral opioids can be avoided by replacing it with an analgesic cocktail locally. Our prospective study was to evaluate the benefits of a periarticular cocktail injection which was given in rheumatoid patients undergoing bilateral TKR in single sitting with respect to pain and knee motion recovery. METHODS: Sixty-four rheumatoid arthritis patients undergoing simultaneous primary total knee replacement were included in the study. A total of 128 knees were randomized either to receive a periarticular intra-operative injection containing ropivacaine, fentanyl, clonidine, cefuroxime and epinephrine (Group A) on one knee and to receive plain ropivacaine (Group B) on the opposite knee. The perioperative and post-operative analgesic regimens were standardized. All patients received the same standard analgesia protocol. Visual analog scores for pain, knee range of motion and quadriceps function were recorded on the day of surgery, first post-operative day, second post-operative day, day of discharge, and 2 weeks and 6 weeks during follow-up. The need for rescue analgesic requirement and adverse effects to the cocktail injection were also noted during the study period. RESULTS: The patients who received the periarticular cocktail fared better in terms of pain scores and functional recovery. Additional rescue agents used were significantly less at 6 h, at 12 h, and over the first 24 h after the surgery in group A when compared with group B. No cardiac or central nervous system toxicity was observed. CONCLUSIONS: Periarticular cocktail injection significantly reduces the requirements for post-operative analgesia and also improves patient satisfaction, with no apparent risks, following total knee arthroplasty in rheumatoid arthritis.
32921825 Subjective sleep disturbances at the time of diagnosis in patients with polymyalgia rheuma 2020 OBJECTIVES: To investigate subjective sleep disturbances in patients with recent-onset polymyalgia rheumatica (PMR) and in patients with recent-onset seronegative elderly-onset rheumatoid arthritis (SEORA). MATERIAL AND METHODS: The study involved patients consecutively referred to two outpatient clinics from January to June 2018, with a diagnosis of PMR according to 2012 European League Against Rheumatism and American College of Rheumatology provisional criteria, and patients with a diagnosis of SEORA according to 1987 American Rheumatism Association criteria + age + absence of rheumatoid factor and anti-citrullinated peptide antibodies. All patients were naive to glucocorticoid (GC) therapy. After informed consent, we asked the patients to fill out a questionnaire including the Medical Outcomes Study - Sleep Scale (MOS-SS), pain Visual Analogic Scale (VAS), Cumulative Illness Rating Scale (CIRS), Neuropsychiatric Inventory (NPI), and how many minutes their morning stiffness (MS) lasted, at baseline and after 1 (T1) and 12 (T2) months. Differences between groups were calculated with the t-test; all p-values were two-sided and p < 0.05 was used to determine statistical significance. The study was approved by the local ethics committee and carried out in accordance with the Helsinki Declaration. RESULTS: The MOS-SS scores and MS duration were the only variables to show at T0 a significant difference between the two groups. In particular, MOS-SS scores were 47.6 ±8.4 (PMR) and 28.26 ±12.4 (SEORA), with p-values = 0.000. The MS duration was 90 ±9.9 minutes and 45 ±5.5 minutes, with p-value = 0.000. At T1 and T2, MOS-SS scores and MS duration decreased in the two groups, and no significant differences were found. CONCLUSIONS: The study suggests that the assessment of subjective sleep disturbances can be useful in the differential diagnosis between recent-onset PMR and SEORA.
32478145 Osteoclasts and their circulating precursors in rheumatoid arthritis: Relationships with d 2020 Jun Patients with rheumatoid arthritis (RA) have very different outcomes, particularly with regard to bone erosions. Since osteoclasts are responsible for bone destruction adjacent to rheumatoid synovium, profiling osteoclasts from circulating precursors in RA could help identify patients at risk for bone destruction. In this study, we sought to determine whether the functional characteristics of osteoclasts generated from their blood precursors were modified by RA activity or were intrinsic to osteoclasts and associated with the RA phenotype (erosive or not). Osteoclasts were generated in vitro from peripheral blood mononuclear cells (PBMCs) of subjects with RA (n = 140), as well as sex- and age-matched healthy controls (n = 101). Osteoclastic parameters were analyzed at baseline and during the follow-up for up to 4 years, with regular assessment of RA activity, bone erosions, and bone mineral density (BMD). As a validation cohort, we examined RA patients from the Early Undifferentiated PolyArthritis (EUPA) study (n = 163). The proportion of CD14(+) PBMC was higher in RA than in control subjects, but inversely correlated with the 28-joint disease activity score (DAS28). Also surprisingly, in osteoclast cultures from PBMCs, active RA was associated with lower osteoclastogenic capacity, while in vitro bone resorption per osteoclast and resistance to apoptosis were similar in both active and quiescent RA. In a small subgroup analysis, osteoclasts from subjects with recent RA that had progressed at four years to an erosive RA exhibited at baseline greater resistance to apoptosis than those from patients remaining non-erosive. Our findings establish that when RA is active, circulating monocytes have a reduced potential to generate osteoclasts from PBMCs in vitro. In addition, osteoclasts associated with erosive disease had resistance to apoptosis from the start of RA.
32765707 Possible association of idiopathic pulmonary hemosiderosis with rheumatoid arthritis: A ca 2020 Sep Idiopathic pulmonary hemosiderosis (IPH) is a rare interstitial lung disease, usually occurring in children or young adults. Although several studies reported on the coexistence of IPH and immune system diseases, the association between these conditions has not been well described. The present study reports on the case of a 21-year-old female patient who presented with bilateral lung abnormalities. The patient was admitted due to a 2-year history of progressive exertional dyspnea, as well as arthralgia and joint swelling in the recent 2 months. During the past 15 years, the patient had been diagnosed with anemia and received repeated blood transfusions. Serial chest CT scans indicated an interstitial pattern. On physical examination, the patient had pale skin with a hemoglobin level of 65 g/l and exhibited finger-clubbing. Arterial blood gas analysis revealed hypoxia. Anticyclic-citrullinated protein antibody and rheumatoid factor were highly positive. Pulmonary function tests revealed restrictive ventilation dysfunction and decreased diffusion capacity. Bronchoscopy and biopsy confirmed diffuse alveolar hemorrhage. Following assessment of the etiology, the diagnosis of IPH was made by exclusion. The patient's symptoms and laboratory findings combined also confirmed the diagnosis of rheumatoid arthritis (RA). After receiving corticosteroid treatment, the patient's condition improved, and she was discharged and followed up. Based on this patient and a review of the literature, the present study demonstrated for the first time that IPH may mediate the development of an RA pathology. Therefore, early diagnosis is important for the timely management of IPH, which may also delay or even prevent the development of immune system diseases, e.g. RA, in patients with IPH. Further attention should be paid to determine the association between IPH and immune system diseases in the clinical setting.
32470883 Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory c 2020 Aug Rheumatoid arthritis (RA) is an autoimmune disorder, in which imbalance in synthesis and production of inflammatory cytokines promotes cartilage and bone destruction. Out of the numerous factors contributing to RA prognosis, the transcription factor NF-kBp65 and p38 mitogen-activated protein kinase (p38MAPK) signaling module has been well implicated as a key regulator of inflammation and downstream signaling events in RA. Stigmasterol (STG) is a natural plant based product exhibiting anti-inflammatory activity, however, the mechanism through which it exhibits anti-inflammatory activity has not been completely understood. The current study aimed to understand the mechanisms underlying the anti-inflammatory effect of STG in the treatment of RA in collagen-induced arthritic (CIA) model of arthritis. Our results showed that STG improved the clinical severity in CIA rats compared to control. The therapeutic effects were related with reduced joint destruction and improved histological alterations. Furthermore, treatment of STG also significantly suppresses the expression of proinflammatory mediators (TNF-α, IL-6, IL-1β, iNOS and COX-2) and increases the expression of anti-inflammatory cytokine (IL-10) through down-regulating the expression of NF-kBp65 (inhibiting p-IKB-α activation) and p38MAPK in joints. In agreement with our results, we can suggest that high therapeutic efficacy of STG against CIA induced inflammation in rats are attributed through the suppressing proinflammatory cytokines.
32782501 Expression levels of CXCR4 and CXCL12 in patients with rheumatoid arthritis and its correl 2020 Sep The present study aimed to investigate the expression levels of C-X-C motif chemokine receptor 4 (CXCR4) and CXC ligand 12 (CXCL12) in patients with rheumatoid arthritis (RA) and the correlation with disease activity. In total, 60 patients with RA were selected as the study group, comprising of 28 patients in active-stage and 32 patients in remission-stage. In addition, 60 patients with osteoarthritis were selected as the control group. Western blotting and ELISA were used to detect the expression of CXCR4 and CXCL12, respectively. The Spearman's correlation test was used to analyze correlations between CXCR4 and CXCL12, and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score 28 (DAS28) scores and rheumatoid factor (RF). The present results suggested that CXCR4 and CXCL12 expression levels in the serum and joint synovial fluid of the study group were significantly higher compared with the control group (P<0.05). Moreover, CXCR4 and CXCL12 expression levels in the RA-active group were higher compared with the remission (P<0.05) and control groups (P<0.01). The Pearson test results suggested that the expression levels of CXCR4 and CXCL12 in the serum and joint synovial fluid of patients with RA had a positive correlation with the ESR, CRP, RF and DAS28 scores (P<0.05). CXCL12 and CXCR4 were highly expressed in the serum and joint synovial fluid of patients with RA, and these expression levels were positively correlated with ESR, CRP, RF and DAS28 scores. Therefore, these clinical parameters may be used as indicators to evaluate the disease activity of patients with RA.
32903777 Recent Advances in the Use of Exosomes in Sjögren's Syndrome. 2020 Sjögren's syndrome (SS) is a chronic autoimmune disorder of the exocrine glands mediated by lymphocytic infiltrates damaging the body tissues and affecting the life quality of patients. Although traditional methods of diagnosis and treatment for SS are effective, in the time of personalized medicine, new biomarkers, and novel approaches are required for the detection and treatment of SS. Exosomes represent an emerging field in the discovery of biomarkers and the management of SS. Exosomes, a subtype of extracellular vesicles, are secreted by various cell types and can be found in most bodily fluids. Exosomes are packed with cytokines and other proteins, bioactive lipids, and nucleic acids (mRNA, circular RNA, non-coding RNA, tRNA, microRNA, genomic DNA, and ssDNA), and transport such cargo between cells. Evidence has indicated that exosomes may play roles in processes such as the modulation of the immune response and activation of inflammation. Moreover, due to features such as stability, low immunogenicity and toxicity, long half-life, and the capacity to penetrate the blood-brain barrier, exosomes have also emerged as therapeutic tools for SS. In this review, we summarize existing literature regarding the biogenesis, isolation, and function of exosomes, specifically focusing on exosomes as novel biomarkers and their potential therapeutic uses in SS.
31628567 Skeletal phenotype/genotype in progressive pseudorheumatoid chondrodysplasia. 2020 Feb BACKGROUND: Axial and extra-axial deceleration in function and progressive joint pain with subsequent development of antalgic gait associated with swellings, and stiffness of the joints with loss of the physiological spine biomechanics were the natural history in this group of patients. Clinical and radiological phenotypes have been analysed carefully to further understand the aetiology behind. METHODS: Seven patients (three children around the age of 9-11 and one child of 17 years old). Three adults aging 25, 30, 33 and 40 years old were seen and examined. The paediatric group of patients were initially diagnosed with myopathy followed later by juvenile rheumatoid arthritis in other institutions. Clinical and imaging documentation were collected in our departments, followed by mutation screening, was carried out by bidirectional sequencing of the WISP3 gene. RESULTS: Clinical and radiological phenotypic studies confirmed the diagnosis of progressive pseudorheumatoid chondrodysplasia. A constellation of abnormalities such as early senile hyperostosis of the spine (Forestier disease), osteoarthritis of the hips showed progressive diminution and irregularities of the hip joint spaces associated with progressive capital femoral epiphyseal dysplasia and coxa vara have been encountered. Loss-of-function homozygous mutations (c.667T>G, p.Cys223Gly) and (c.170C>A, p.Ser57*) in the WISP3 gene were identified in our patients. CONCLUSION: The definite diagnosis was not defined via vigorous myopathic and rheumatologic investigations. Detailed clinical examination and skeletal survey, followed by genotypic confirmation, were our fundamental pointers to rule out the false diagnosis of juvenile rheumatoid arthritis and rheumatoid polyarthritis in the adult group of patients. We wish to stress that the clinical/radiological phenotype is the baseline tool to establish a definite diagnosis and to guide the geneticist toward proper genotype.Key Points•Joint pain and difficulties in walking/climbing the stairs are characteristic features encountered in early childhood. False diagnosis of juvenile rheumatoid arthritis can be made at this point.•False positive-like muscular wasting resembling myopathy results in ensuing vigorous troublesome investigations.•Flattened vertebral bodies associated with defective ossification of the anterior end plates are characteristic features of progressive pseudorheumatoid chondrodysplasia.•Joint expansions, which are usually accompanied by narrowing of the articular ends of the appendicular skeletal system, show a clear radiological phenotype of pseudorheumatoid chondrodysplasia.
32627210 New developments in esophageal function testing and esophageal manifestations of connectiv 2020 Dec This work summarizes new and emerging metrics and tools in esophageal function testing and their potential clinical impact. Because the diagnostic sensitivity and reliability of conventional impedance-pH variables are suboptimal, several novel impedance parameters, such as the postreflux swallow-induced peristaltic wave index and the mean nocturnal baseline impedance, as well as mucosal impedance, are entering a validation stage prior to general clinical use. The accurate diagnosis of behavioral disorders in patients with rumination syndrome and supragastric belching using ambulatory multiple intraluminal impedance-pH can lead directly to behavioral interventions in patients with refractory gastroesophageal reflux disease (GERD). New provocative measures, such as multiple rapid swallows and the rapid drink challenge, have been developed to overcome the limitations of standard high-resolution esophageal manometry, aiming at further clarifying esophageal dysmotility. Furthermore, the current diagnostic and therapeutic challenges in patients with esophageal involvement in Sjogren's syndrome and scleroderma, who tend to have severe forms of GERD, are entering a new investigative and clinical phase.
33025900 Digestive involvement in primary Sjögren's syndrome: analysis from the Sjögrenser regist 2020 Jul OBJECTIVES: Digestive involvement (DI) has been reported in 10-30% of primary Sjögren's syndrome (pSS) patients, and few studies have systematically analysed the prevalence of DI in pSS patients. The aim of this study was to describe DI prevalence in pSS patients from the Sjögrenser Study, and to analyse its clinical associations. METHODS: All patients included in the Sjögrenser study, a Spanish multicentre randomised cohort, containing demographic, clinical and histologic data, have been analysed retrospectively. Patients were classified according to the presence of DI (oesophageal, gastric, intestinal, hepatic and pancreatic), and we have performed DI clinical associations, descriptive statistics, Student t or χ2 test, and uni and multivariate logistic regression. RESULTS: From 437 included patients, 95% were women, with a median age of 58 years, 71 (16.2%) presented DI: 21 (29.5%) chronic atrophic gastritis, 12 (16.9%) oesophageal motility dysfunction, 3 (4.2%) lymphocytic colitis, 18 (25.3%) primary biliary cholangitis, 15 (21.1%) autoimmune hepatitis, 7 (9.8%) pancreatic involvement and 5 (7%) coeliac disease. Half of them developed DI at the same time or after pSS diagnosis. Patients with DI were significantly older at pSS diagnosis (p=0.032), more frequently women (p=0.009), presented more autoimmune hypothyroidism and C3 hypocomplementaemia (p=0.040), and were treated more frequently with glucocorticoids, immunosuppressant and biologic therapies. Patients with pancreatic involvement presented more central nervous system and renal involvement, Raynaud's phenomenon, lymphoma and C3/C4 hypocomplementaemia. CONCLUSIONS: DI is frequent in Sjögrenser patients, mainly in the form of autoimmune disorders, and seem to be associated with a more severe phenotype. Our results suggest that DI should be evaluated in pSS patients, especially those with more severe disease.
32108012 Scenario of the Treatment of Arthritis with Natural Products. 2020 BACKGROUND: Conventional treatments of arthritis use toxic and poorly tolerated drugs. Therefore, natural products are an alternative because they are important sources of bioactive substances with therapeutic potential. OBJECTIVE: To perform synthesis of patent applications associated with the use of natural products in the technological development of the invention for use in treating arthritis. METHODS: The search for patents was conducted using the following databases of World Intellectual Property Organization (WIPO), European Patent Office (EPO, Espacenet), United States Patents and Trademark Office (USPTO) and National Institute of Intellectual Property (INPI) using as keywords - arthritis, treatment and the International Patent Classification (IPC) A61K36 / 00. RESULTS: A total of 617 patents related to the subject were registered in the period available in patents databases during the study period from the years 2005 to 2017, of which 44 were analyzed based on the established inclusion criteria. The most important countries for protecting these inventions were China, followed by the United States of America, the Republic of Korea and Japan. As for the typology of depositors, that were identified by Educational Institutions and Public Institutes of Research (IEIPP) and Companies and Private Research Institutes (EIPP). CONCLUSION: The analysis of patents made it possible to characterize the natural products used in the treatment of arthritis, with emphasis on botanical extracts (71%), as a single component, as well as in association with other botanical extracts, isolated compounds and minerals.
33195348 The Role of Ultrasound Across the Inflammatory Arthritis Continuum: Focus on "At-Risk" Ind 2020 In individuals at-risk of developing inflammatory arthritis, the value of an ultrasound (US) scan assessment to predict progression has been demonstrated repeatedly. However, depending on recruitment criteria, these individuals may be at different stages in the arthritis development continuum, therefore representing a heterogeneous population. As a consequence, the predictive value of ultrasound results may differ between cohorts. As other reviews have focused on the challenges in population recruitment or have combined biomarkers predicting value according to one recruitment pathway, we wanted to focus on the sole use of ultrasound assessment and its variation according to population recruitment criteria. In this review, we discuss the use of ultrasound in the different at-risk populations across the inflammatory arthritis disease continuum. This review demonstrates that although some sub-population data is scarce, ultrasound is best predictive in three at-risk populations: those with a positive ACPA test in the context of non-specific MSK symptoms, those with clinically suspect arthralgia and those with palindromic rheumatism. We consider that ultrasound assessment will be a cornerstone in prediction risk modeling and prevention studies of the preclinical phases of IA in the future.
32522598 Appropriateness of laboratory tests in the diagnosis of inflammatory rheumatic diseases am 2020 Dec INTRODUCTION: Autoantibody tests are commonly ordered when screening for rheumatic diseases. Rheumatoid factor (RF) and antinuclear antibody (ANA) have low positive predictive values in general practice. Overuse of diagnostic tests can result in an increase in unnecessary referrals, patient anxiety, and further costs. OBJECTIVE: The objective was to evaluate the utilization patterns, appropriateness, and associated costs of tests including ANA, extractable nuclear antibodies (ENA), anti-double stranded DNA (anti-dsDNA), RF, and HLA-B27 in patients referred to rheumatologists. METHODS: A review was conducted of consecutive referrals (accepted and rejected) using university rheumatologists' practices over one year. Inappropriate investigations, and associated costs were analyzed. Tests were considered appropriate if at least one criterion for a specific disease was provided. RESULTS: Of 638 referrals the most common reported reasons for referral were: spondyloarthropathies (SpA), rheumatoid arthritis (RA), and lupus (SLE). Prior to referral: 61% had undergone ANA testing at least once, ANA was repeated in one third; 19% had ENA and 21% had anti-dsDNA. 20% had ANA testing with no clinical indication. Half of ENA and anti-dsDNA testing was in the context of a negative ANA. RF was requested in 65% and in close to one third, there was no clinical suspicion of inflammatory arthritis. CONCLUSION: Despite the recommendations by CRA Choosing Wisely Campaign, at least 50% of laboratory investigations, including RF, ANA, ENA, and anti-dsDNA, are inappropriately ordered. More selective ordering of the above tests would lead to marked cost reduction.
33343379 Histone Deacetylase 3-Mediated Inhibition of microRNA-19a-3p Facilitates the Development o 2020 Histone deacetylase (HDAC) has been implicated in rheumatoid arthritis (RA) progression. We investigated the roles of histone deacetylase 3 (HDAC3) involved in RA-associated interstitial lung disease (ILD) fibrosis. Firstly, we measured the expression of HDAC3 and interleukin 17 receptor A (IL17RA) in lung tissue samples from normal controls, idiopathic pulmonary fibrosis (IPF) patients, and RA-ILD patients. Next, chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay were employed to detect the interaction between HDAC3 and microRNA-19a-3p (miR-19a-3p) and between miR-19a-3p and IL17RA. Further, immunohistochemistry was used to localize HDAC3 and IL17RA expression in lung tissues. Additionally, functional assays were conducted followed by expression determination of HDAC3, miR-19a-3p, and IL17RA with reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis. The effect of HDAC3 on RA-ILD in the constructed RA-ILD mouse model was also studied based on arthritis assessment. We found overexpressed HDAC3 and IL17RA as well as silenced miR-19a-3p in RA-ILD mouse model and RA-ILD patients. In the mouse model, HDAC3 downregulated miR-19a-3p in lung fibroblasts to promote the progression of RA-ILD fibrosis. In lung fibroblasts of RA-ILD mice, IL17RA was a target gene of miR-19a-3p. miR-19a-3p negatively regulated IL17RA, thereby increasing the expression of fibrosis markers, COL1A1, COL3A1, and FN, in lung fibroblasts of mice. Taken together, HDAC3 upregulated IL17RA expression by targeting miR-19a-3p to facilitate the RA-ILD fibrosis development, which sheds light on a new HDAC3/miR-19a-3p/IL17RA axis functioning in RA-ILD fibrosis.