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

ID PMID Title PublicationDate abstract
31783137 Zishen Tongluo formula ameliorates collagen-induced arthritis in mice by modulation of Th1 2020 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Zishen Tongluo formula (ZTF) is simplified from the Qingluo Tongbi formula, which has been applied to treat rheumatoid arthritis (RA) in clinical practices for several decades. Our previous studies have verified the effects of ZTF on arthritis animal models. However, its mechanism of treating RA is not clear. AIM OF THE STUDY: The present study was designed to investigate the effects of ZTF on the Th17/Treg balance in RA mice and the role of the different herb groups with the effect of Zishen yangyin (YY), Huatan quyu (HT), or Qufeng chushi (QF) in ZTF. MATERIALS AND METHODS: A mouse model of collagen-induced arthritis (CIA) was established. The animals were randomly divided into the normal, model, positive drug, YY, QF, HT, and the whole compound (ZTF) groups. After oral administration for one-month, cytokine levels in the plasma and histopathological changes of the joint were measured by ELISA and hematoxylin-eosin staining, respectively. Meanwhile, the balance of Th17/Treg cells in blood, spleen or lymph nodes was detected using flow cytometry and qPCR. RESULTS: ZTF or the different functional groups could improve the joint inflammation, decrease the levels of proinflammatory cytokines, restore the balance of Th17 and Treg cells in CIA mice. However, there were some differences in each functional group: YY mainly promoted the responses of Treg cells while QF inhibited the functions of Th17 cells. Besides, HT regulated both Th17 and Treg cells to keep the immune balance. CONCLUSIONS: ZTF could notably ameliorate CIA mice by restoring the balance of Th17/Treg cells. Each functional group could target Th17 and/or Treg cells to produce synergistic/enhancement effects, and ZTF had a better holistic effect in RA treatment.
29862859 ABBV-105, a selective and irreversible inhibitor of Bruton's tyrosine kinase, is efficacio 2019 May OBJECTIVES: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase required for intracellular signaling downstream of multiple immunoreceptors. We evaluated ABBV-105, a covalent BTK inhibitor, using in vitro and in vivo assays to determine potency, selectivity, and efficacy to validate the therapeutic potential of ABBV-105 in inflammatory disease. METHODS: ABBV-105 potency and selectivity were evaluated in enzymatic and cellular assays. The impact of ABBV-105 on B cell function in vivo was assessed using mechanistic models of antibody production. Efficacy of ABBV-105 in chronic inflammatory disease was evaluated in animal models of arthritis and lupus. Measurement of BTK occupancy was employed as a target engagement biomarker. RESULTS: ABBV-105 irreversibly inhibits BTK, demonstrating superior kinome selectivity and is potent in B cell receptor, Fc receptor, and TLR-9-dependent cellular assays. Oral administration resulted in rapid clearance in plasma, but maintenance of BTK splenic occupancy. ABBV-105 inhibited antibody responses to thymus-independent and thymus-dependent antigens, paw swelling and bone destruction in rat collagen induced arthritis, and reduced disease in an IFNα-accelerated lupus nephritis model. BTK occupancy in disease models correlated with in vivo efficacy. CONCLUSION: ABBV-105, a selective BTK inhibitor, demonstrates compelling efficacy in pre-clinical mechanistic models of antibody production and in models of rheumatoid arthritis and lupus.
31154267 A selective CB(2) agonist protects against the inflammatory response and joint destruction 2019 Aug Rheumatoid arthritis (RA) is a chronic, inflammatory, synovitis-dominated systemic disease with unknown etiology. RA is characterized by the involvement of multiple affected joints, symmetry, and invasive arthritis of the limbs, which can lead to joint deformity, cartilage destruction, and loss of function. Cannabinoid receptor 2 (CB(2)) has potent immunomodulatory and anti-inflammatory effects and is predominantly expressed in non-neuronal tissues. In the current study, the role of CB(2) in the process of inflammatory bone erosion in RA was examined. The selective agonist or high-affinity ligand of CB(2) (4-quinolone-3-carboxamides CB2 agonist, 4Q3C CB(2) agonist, 4Q3C) significantly reduced the severity of arthritis, decreased histopathological findings, and markedly reduced bone erosion in collagen-induced arthritis (CIA) mice. In addition, 4Q3C prevented an increase in the nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and inhibited the formation of osteoclasts in CIA mice. Furthermore, the expression of tumor necrosis factor-alpha, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase was lower in 4Q3C-treated CIA mice than in control CIA mice. Micro-computed tomography corroborated the finding that 4Q3C reduced joint destruction. These data clearly indicate that the CB(2)-selective agonist, 4Q3C, may have anti-inflammatory and anti-osteoclastogenesis effects in RA and may be considered to be a novel treatment for RA.
31328022 Why Don't We Have a Vaccine Against Autoimmune Diseases? - A Review. 2019 This review examines some of the reasons why we don't have a vaccine against autoimmune diseases and highlights the progress that has been made. Many autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS) and type 1 diabetes (T1D), are driven by autoimmune T cell responses. Unlike vaccines for most infectious diseases, which elicit antibody responses, are intended for immuno-naive individuals and considered preventative, a vaccine for an autoimmune disease must be therapeutic and resolve or control the on-going autoimmune response and condition in the diseased host. Despite these differences, many of the same considerations for infectious disease vaccines must also be addressed to develop a therapeutic vaccine for autoimmune diseases. The disease initiator/triggers, antigens and autoantigens, nature of the immunopathogenic and protective/therapeutic immune response will be compared for infectious and autoimmune diseases as will approaches for developing vaccines including formulations, animal models and indicators of success. The rationale for a therapeutic vaccine for RA will be discussed in greater detail with a relatively limited discussion of T1D, MS and other autoimmune diseases.
32373270 Rheumatoid Meningitis: Clinical Characteristics, Diagnostic Evaluation, and Treatment. 2020 Apr BACKGROUND AND PURPOSE: Due to the potential for high mortality and neurologic complications of rheumatoid meningitis (RM), awaiting biopsy confirmation may delay vital treatment intervention. Our aim was to describe the clinical presentations of RM in our population and determine whether meningeal biopsy impacted diagnosis, treatment, and outcomes. METHODS: A retrospective chart review was completed for patients at Mayo Clinic with a diagnosis of RM within the last 28 years. Those with identified alternative inflammatory, infectious, or neoplastic causes of pachymeningitis or leptomeningitis were excluded. RESULTS: Fourteen patients meeting inclusion/exclusion criteria were identified. All patients were positive for rheumatoid factor or cyclic citrullinated peptide. All patients had magnetic resonance imaging abnormalities characterized by pachymeningeal and/or leptomeningeal enhancement. Of the 10 patients who underwent biopsy, nonspecific findings were seen in 74%. All patients except one were treated with corticosteroids with subsequent symptomatic improvement. Radiographic improvement or resolution was seen in 10 (83%) of 12. Patients improved with corticosteroid treatment, including those who were diagnosed with RM on clinical basis without undergoing a biopsy as well. CONCLUSIONS: This retrospective review displays the myriad of clinical presentations of RM. It also suggests that with appropriate exclusion of infectious, neoplastic, and other autoimmune etiologies, biopsy may not be necessary to initiate treatment.
31399351 Role of rheumatoid factor isotypes and anti-citrullinated peptide antibodies in the differ 2021 Jan BACKGROUND/OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by swelling, tenderness and destruction of synovial joints, leading to severe disability and premature mortality. The aim of the study was to determine the diagnostic accuracy of the 3 isotypes of rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA) and the combination of both, for the diagnosis of rheumatoid arthritis (RA) in non-selected patients with inflammatory arthralgia. METHODS: We include 129 patients with inflammatory Arthalgia from a third level reference Center of rheumatic diseases in Monterrey, México. Their samples were analyzed for RF isotypes (IgA, IgG, and IgM) by ELISA (EUROINMUN), using a cut-off of 20IU/ml, and for ACPA's 5IU/ml; a medical examination was performed to obtain the definitive diagnoses of the patients. Data analysis was carried out using ROC curves for the measurement of sensitivity, specificity, for diagnostic accuracy to verify if the use of 3 RF isotypes and ACPA had a better prediction for the diagnosis of RA than use only one isotype and the ACPA alone. RESULTS: The ROC showed a sensitivity and specificity of the different antibodies with different cut-off points, being the best for the IgM with 0.802 followed by ACPA, IgA and IgG with 0.771, 0.63, and 0.728 respectively without statistical difference, the sensitivity and specificity of the combination of the 4 antibodies were 81.4 and 73.66%. CONCLUSION: In non-selected patients with inflammatory arthralgia, the combination of ACPA and isotypes of RF did not demonstrate more sensibility and specificity than IgM isoform of rheumatoid factor measurement only. We recommend that in the clinical scenario of arthralgia, where the diagnoses are Lupus, Sjogren syndrome and Osteoarthritis, RF IgM isoform is used followed by ACPA.
32524079 SB4 in the Era of Biosimilars: Clinical Data and Real-World Experience. 2019 Jun A biosimilar is a biological medicinal product that is highly similar to an already authorized original biological medicinal product. The introduction of biosimilars may allow for a reduction in health care costs, due to discount pricing. Current clinical studies and real-world data suggest that the biosimilar SB4 is equivalent to etanercept with respect to efficacy and safety. Additional real-world safety data for SB4 via pharmacovigilance studies are needed to draw conclusions regarding the risks of rare adverse events such as serious infections and malignancy. Clinical trial design of biosimilars should be standardised to improve consistency, increase confidence and facilitate interpretation of data. Where there are health economic advantages of switching from originator to biosimilar, patients should be appropriately informed, and, ideally, in order to minimise nocebo responses and maximise benefit, switching should be undertaken by shared decision-making between the physician and patient on a case-by-case basis.
31683983 Prevotella Copri and Microbiota in Rheumatoid Arthritis: Fully Convincing Evidence? 2019 Nov 1 : Gut microbiota regulates the host's immune system. Microorganisms and their compounds can co-exist peacefully with the immune system and coordinate its function and regulation. Some microbial clusters may be harmful and others helpful in the respective negative or positive balance of the immune network. These insights have revealed important mechanisms for understanding and treating autoimmune and inflammatory diseases. This Editorial aims to clarify the role of specific genus of gut microbiota, such as Prevotella, in influencing the pathogenesis of Rheumatoid Arthritis (RA).
31742964 2019 Sep The objective of the current review is to perform a systematic review of the beneficial and harmful effects of baricitinib 2 mg orally once daily in combination with methotrexate(MTX) (or as monotherapy in cases of intolerance to MTX) for the treatment of adult patients with moderate-to-severe rheumatoid arthritis who have responded inadequately to one or more disease-modifying antirheumatic drugs.
31564291 Treat to Target in Rheumatology: A Historical Account on Occasion of the 10th Anniversary. 2019 Nov Chronic immune-mediated rheumatic diseases are characterized by inflammatory signs and symptoms, damage to joints, or spine and physical disability. In all these diseases the adverse outcomes are related to the degree of the inflammatory response and the duration of the high inflammatory situation. A state in which inflammation is minimized or eliminated is the therapeutic goal, but the time to reach such a state is also essential. Repeated treatment adaptations in the course of regular clinical assessments of disease activity are essential until the desired, predefined state is achieved. This approach constitutes the treat-to-target concept.
31529278 Comparative Disease Burden in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, or 2019 Dec INTRODUCTION: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are three common inflammatory rheumatic diseases that can lead to deformities and joint destruction. Few studies have compared disease burden across patients with these diseases. The objective of this study was to compare disease burden in patients with RA, PsA, or axSpA in routine US clinical practice. METHODS: This study included adults with RA, PsA, or axSpA enrolled in the Corrona RA and PsA/SpA registries between March 2013 and March 2018. Patient and clinical characteristics at enrollment were compared between patients with RA vs. PsA and RA vs. axSpA using t tests or Wilcoxon rank-sum tests for continuous variables and χ(2) or Fisher's exact tests for categorical variables. RESULTS: A total of 11,350 patients with RA, 2003 with PsA, and 495 with axSpA were included. Patients with RA had shorter mean symptom and disease duration (9.4 and 7.6 years, respectively) than those with PsA (11.2 and 8.4 years) or axSpA (16.7 and 9.8 years). Patients with PsA had lower mean physician global assessment (18.6 vs. 27.3), higher patient global assessment (43.2 vs. 36.9), comparable pain (38.9 vs. 39.5), and lower fatigue (41.1 vs. 43.4) scores than those with RA. Patients with axSpA had comparable mean physician global assessment (25.5 vs. 27.3) and higher patient global assessment (50.2 vs. 36.9), pain (46.1 vs. 39.5), and fatigue (48.3 vs. 43.4) scores than those with RA. CONCLUSIONS: Disease burden in patients with PsA or axSpA was comparable to or greater than that in patients with RA on the basis of common patient-reported outcome measures but appeared lower when assessed using RA disease activity measures, suggesting that disease-specific approaches to care are needed to optimize disease management. FUNDING: This study was sponsored by Corrona, LLC, and financial support was provided by Novartis. The Rapid Service Fee was funded by Novartis. Plain language summary available for this article.
30915626 Decreased Injection Site Pain Associated with Phosphate-Free Etanercept Formulation in Rhe 2019 Jun INTRODUCTION: Etanercept, a tumor necrosis factor inhibitor, is used to treat rheumatoid arthritis (RA) and psoriatic arthritis (PsA), and is administered via subcutaneous injection. Injection site pain (ISP) associated with subcutaneous administration may affect compliance or hinder initiation of prescribed medications. To improve the patient experience, a new phosphate-free formulation of etanercept was evaluated for reduced ISP associated with administration. METHODS: This phase 3b, multicenter, randomized, double-blind, cross-over study compared the prior formulation of etanercept to a phosphate-free formulation. Etanercept-naïve adults with RA or PsA indicated for treatment with etanercept were eligible. Patients were randomized (1:1) to receive both etanercept formulations (50 mg) in one of two crossover sequences: prior formulation followed by phosphate-free formulation (sequence AB) or phosphate-free formulation followed by prior formulation (sequence BA) at visits 1 week apart. Patients self-reported ISP using a fit-for-purpose 100-mm visual analog scale within 30 s after injection. Safety outcomes included incidence of treatment-emergent adverse events. Mixed-effects analysis of variance model was used to assess ISP, with treatment, study period, sequence, and disease indication as fixed-effect covariates and patient-within-sequence as random effect. RESULTS: A total of 111 patients enrolled (56 sequence AB; 55 sequence BA). Mean ISP score for prior formulation was 23.1 mm and for phosphate-free formulation was 19.1 mm (mean difference - 4 mm; 95% confidence interval: - 8.0, 0.0; P = 0.048). Patients with the highest ISP scores from the prior formulation (by quartile cut points) had the largest reduction in pain with phosphate-free formulation. Injection site reactions were few in number and similar between formulations; no new safety signals were observed. CONCLUSIONS: The new phosphate-free formulation of etanercept had statistically significantly lower mean pain scores than the prior formulation, with largest pain reductions observed among patients who reported highest pain with the prior formulation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02986139. FUNDING: Amgen Inc, Thousand Oaks, CA USA.
31746064 Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine lev 2020 May Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.
32116681 Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthriti 2019 Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered via gastric gavage started prior to or at the time of CIA induction. Gut microbiota were evaluated with 16S rRNA gene sequencing from fecal pellets collected prior to arthritis induction, during onset of arthritis, and after treatment. Immune response was evaluated by measuring changes in T helper-17 (Th17) and T regulatory (Treg) cells in the spleen and intestine, as well as serum cytokine levels. Before induction of CIA, acarbose significantly reduced the incidence of arthritis and attenuated clinical severity of arthritis. The frequency of Th17 cells was significantly decreased in the intestinal lamina propria in acarbose treated mice. Mice that were treated with acarbose showed significantly increased CD4(+)CD25(+)Foxp3(+) Treg cells with elevation of Helios and CCR6. A remarkable alteration in microbial community was observed in acarbose treated mice. Bacterial diversity and richness in mice with arthritis were significantly lower than those in acarbose treated groups. The frequency of Firmicutes was significantly reduced after arthritis onset but was restored after treatment with acarbose. The frequency of Lactobacillus, Anaeroplasma, Adlercreutzia, RF39 and Corynebacterium was significantly higher in control groups than in acarbose treated, while Oscillospira, Desulfovibrio and Ruminococcus enriched in acarbose treated group. Miglitol, another α-glucosidase inhibitor showed a similar but less potent anti-arthritic effect to that of acarbose. These data demonstrate that acarbose alleviated CIA through regulation of Th17/Treg cells in the intestinal mucosal immunity, which may have resulted from the impact of acarbose on gut microbial community. Inexpensive antidiabetic drugs with an excellent safety profile are potentially useful for managing rheumatoid arthritis.
31475016 Corrigendum: Rheumatoid Synovial Fluids Regulate the Immunomodulatory Potential of Adipose 2019 [This corrects the article DOI: 10.3389/fimmu.2019.01482.].
31104879 Frequency of ANA/DFS70 in Relatives of Patients with Rheumatoid Arthritis Compared to Pati 2021 Feb INTRODUCTION: DFS70 ANAs have attracted interest due to their frequency in individuals with no clinical evidence of systemic autoimmune rheumatic disease, groups with genetic risk for rheumatoid arthritis (RA) were not assessed. OBJECTIVE: To determine the frequency of ANA and DFS70 ANA in blood relatives (BR) of people with RA compared to patients with early RA (ERA), and control individuals, and its association with health status. METHODOLOGY: A cross-sectional study with an analytical component. Sixty ERA patients, 60 BR and 120 control individuals paired by age and sex were studied. Hep2-ANA and DFS70 ANA were studied. The absolute and relative frequencies and associations were established using logistic regression models, with a significance level of 95%. RESULTS: 43% ANA in ERA, 30% in BR, and 25.8% in control individuals 1:80. The fine dense granular pattern based on conventional Hep2 was found in 12.9% of the positive samples, and 1.66% of the total samples. There was no detection of DFS70 ANAs in patients with ERA. In ERA there was an association between the presence of ANA and inflamed joints (p=.02), CRP (p=.01), DAS28CRP (p=.03) and HAQ (p=.04). There was an association between ANA and elevated CRP (p=.05) in the BR. In the control individuals, there was an association between ANA and painful joints (p=02). In DFS70 ANA individuals we observed an association between a normal ESR p=.032, BR (-), p=.044 and absence of painful joints, p=.039. CONCLUSIONS: The frequency of DFS70 ANA in the groups studied was low, none of the patients with ERA was positive. The presence of DFS70 ANA was only confirmed in systemically healthy individuals.
31385264 Patient Perceptions of Unmet Medical Need in Rheumatoid Arthritis: A Cross-Sectional Surve 2019 Sep INTRODUCTION: Many rheumatoid arthritis (RA) patients do not achieve their treatment goals and experience symptoms that affect psychosocial outcomes and daily activities. This study aimed to identify and quantify the unmet needs perceived by US patients with RA currently taking a disease-modifying antirheumatic drug (DMARD). METHODS: A cross-sectional, web-based survey was conducted with RA patients recruited through CreakyJoints, an online patient support community, and ArthritisPower(®), an online patient research registry, from December 2017 to January 2018. Participant patients were aged ≥ 21 years, failed ≥ 1 DMARDs, and were receiving their current DMARD(s) for ≥ 6 months; they answered 50 questions about treatment history, RA symptoms, and flares and completed the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire and the Treatment Satisfaction Questionnaire for Medication (TSQM). Treatment satisfaction was defined by a TSQM global satisfaction score ≥ 80. RESULTS: Of 415 patients screened, 258 (62%) were eligible and completed the survey; 87% were women, and 87% white, with mean (SD) age of 54.5 (11.4) years. A total of 232 patients (90%) had current or past biologic DMARD (bDMARD) use, with 67% currently on a bDMARD, 65% on ≥ 1 conventional synthetic DMARD, and 40% on methotrexate. Forty-three percent of patients reported daily/almost daily use of prescription pain medications, and 44% reported a current flare. Mean (SD) TSQM scores were 59 [20] for effectiveness, 59 [26] for side effects, 72 [18] for convenience, and 65 [21] for global satisfaction. The mean (SD) RAID overall score was 5.1 (2.0) on a 0-10 scale. Only 26% (67 patients) were satisfied with their RA treatment. Patients not satisfied with treatment reported higher RAID scores overall and by domain, and approximately half reported a current flare. CONCLUSIONS: Results from this real-world survey suggest that three-fourths of RA patients are not satisfied with treatments, which include bDMARDs. Patients continued to experience bothersome symptoms that impacted their daily activities and life. There remains a need for improved disease management among currently treated RA patients. FUNDING: Eli Lilly and Company (Indianapolis, IN, USA).
31456861 The Correlation Between Tenosynovitis Pattern on Two-Phase Bone Scintigraphy and Clinical 2019 Aug PURPOSE: To investigate the correlation between the tenosynovitis pattern on two-phase bone scintigraphy (2P-BS) and clinical manifestation in patients with suspected rheumatoid arthritis (RA). METHOD: 2P-BS including technetium-99m-methylene diphosphonate blood pool and bone phase imaging in 402 consecutive patients with clinically suspected RA were retrospectively reviewed. According to 2010 RA Classification Criteria, patients were grouped as RA and non-RA. Visual assessment of all fingers, toes, wrists, and ankles on 2P-BS was performed. Clinical suspected tenosynovitis was evaluated on physical examination. Rheumatoid factor, anti-cyclic citrullinated protein antibody, C-reactive protein, and estimated sedimentation rate were obtained. Radiographic findings were also used to define early and established arthritis. RESULTS: Tenosynovitis pattern was detected in 12.7% (51/402 patients) on 2P-BS. A total of 94.1% (48/51) were diagnosed as RA vs. 5.9% (3/51) as non-RA. Of the 48 RA patients with positive 2P-BS finding, 85.4% (41/48) had early arthritis and 14.6% (7/48) had established arthritis. On physical examination, tenosynovitis was suspected in 21.9% (88/402). A total of 56.8% (50/88) belonged to the RA group and 43.2% (38/88) to the non-RA group. The tenosynovitis pattern of 2P-BS and physical examination showed statistical difference and moderate agreement. The positive tenosynovitis pattern on 2P-BS represented up to 26.408 of odds ratio which was highest among the RA-associated factors. CONCLUSION: Tenosynovitis pattern on 2P-BS was more commonly detected in the RA group and was more frequently associated with early arthritis pattern. Therefore, 2P-BS could give additional information for the detection of subclinical tenosynovitis in early or preclinical RA patients.
30988781 Investigation of gene expression profiles in a rat adjuvant arthritis model suggests an ef 2019 May Rheumatoid arthritis (RA) is a common systemic autoimmune disease mainly involving the formation of a synovial pannus, for which no effective treatment is available. In order to study the molecular biological mechanisms underlying the inhibition of RA synovial pannus by triptolide, differentially expressed genes in synovial tissues from an adjuvant arthritis (AA) rat model with and without triptolide treatment were detected in an mRNA microarray profile produced by Agilent Technologies and verified by reverse transcription-quantitative polymerase chain reaction analysis (RT-qPCR). An AA model was established by subcutaneously injecting 0.1 ml Freund's complete adjuvant daily for 18 days and scored by arthritis index assessment. Subsequently, triptolide (0.4 mg/kg) or an equivalent amount of saline was administered daily for 14 days. At the end of the experiment, synovial tissues were obtained from the ankle joints of the rats' hind legs. Total RNA was extracted and purified, and microarray hybridization was used to obtain the gene expression profile for RA with and without triptolide treatment. A total of 48 genes were identified to be differentially expressed between the treatment and model groups, including 32 upregulated and 16 downregulated genes. The possible signaling pathways associated with the effect of triptolide were investigated by Gene Ontology and pathway analysis, revealing that the phosphoinositide-3 kinase (PI3K)/AKT signaling pathway has a key role in the proliferation and apoptosis of synovial cells in RA joints. Reverse transcription-quantitative polymerase chain reaction analysis was applied to confirm the aberrant expression of key mRNAs and revealed that vascular endothelial growth factor (VEGF) A and C1q and tumor necrosis factor related protein 3 (C1QTNF3) were downregulated in the treatment group compared with the model group (P<0.05). In conclusion, triptolide may exert its effects against RA via the PI3K/AKT pathway and has an inhibitory effect on the expression of VEGFA and C1QTNF3, thus are potentially associated with the occurrence and development of RA.
31364981 Comprehensive review of current diagnostic and treatment approaches to interstitial lung d 2019 Jul Interstitial lung disease (ILD) is one of the extra-articular involvement forms of rheumatoid arthritis (RA), and it is associated with increased mortality. The presence of genetic susceptibility, smoking, rheumatoid factor positivity, and the presence of anticitrulline peptide antibodies are factors contributing to the development of ILD in patients with RA. Early diagnosis and treatment of ILD contribute to the reduction of morbidity and mortality. We herein evaluated the current literature for the diagnosis and treatment of RA-associated ILD.