Browse

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

ID PMID Title PublicationDate abstract
31956018 Synovial fibroblasts and articular tissue remodelling: Role and mechanisms. 2020 May Synovial joints are unique functional elements of the body and provide the ability for locomotion and for physical interaction with the environment. They are composed of different connective tissue structures, of which the synovial membrane is one central component. It shows a number of peculiarities that makes it different from other membranes in our body, while several lines of evidence suggest that synovial fibroblasts, also termed fibroblast-like synoviocytes (FLS) critically contribute to these peculiarities. This becomes evident particularly under disease conditions such as in rheumatoid arthritis and osteoarthritis, where the synovium is a key pathophysiological component. Therefore, an in-depth knowledge of FLS biology is not only important for understanding key features of articular function but also provides explanations for important characteristics of both degenerative and inflammatory joint diseases. This article reviews the structure, biochemical composition and functions of the synovial membrane and by focusing on the role of synovial fibroblasts explains key features of articular tissue remodelling particularly under disease conditions.
32297483 Update on disease pathogenesis, diagnosis, and management of primary Sjögren's syndrome. 2020 Jun Primary Sjögren's syndrome (pSS) is a typical multisystem disease, characterized by lymphocytic infiltration of the exocrine glands leading to glandular dysfunction. Multiple systemic manifestations occur in those of serious conditions, with different courses and outcomes. Its pathogenesis is complex, and its diagnosis and management are being constantly updated and improved. We have failed to have much progress in targeted immunotherapy for pSS, and as yet this is still based on empirical treatment. Many studies have tried to define pSS more accurately, to study its pathogenesis, to find effective treatment strategies, opening up new avenues for early diagnosis and precise management of pSS.
33235841 Association of Psoriasis with Autoimmune Disorders: Results of a Pilot Study. 2020 Sep BACKGROUND: Association of psoriasis with other autoimmune diseases remains an ongoing research subject. OBJECTIVES: To investigate the association of psoriasis with other autoimmune disorders. MATERIALS AND METHODS: We studied 80 (M: F 57:23) psoriasis patients aged 13-75 years for concurrent autoimmune disorders. After clinical examination, hemogram, fasting blood sugar, HbA1c, thyroid function tests, anti-TPO antibody, rheumatoid factor, anti-tTG antibody, anti-CCP antibody, ANA, anti-dsDNA antibody, anti-Ro antibody, and fecal calprotectin were estimated. RESULTS: Mild-to-moderate and severe psoriasis was present in 86.3% and 13.8% patients, respectively. Psoriatic arthritis was present in 3.8% patients, all of whom also had severe psoriasis. Only 37 (46.3%) patients had clinical and/or sero-abnormality suggestive of autoimmune disorders; vitiligo in 3.8%, type-1 diabetes mellitus (DM) in 1.3%, and type-2 DM in 6.3% patients. Sero-positivity reflecting subclinical autoimmunity was noted for anti-CCP antibodies (in 2.5%), rheumatoid factor (in 2.5%), hypo- or hyper-thyroidism (in 8.8%), anti-TPO antibodies (in 5.0%), anti-tTG antibody (in 1.3%), ANA (in 5.0%), anti-dsDNA antibody (in 2.5%), and anti-Ro antibody in 11.3% patients. Elevated fecal calprotectin levels suggestive of inflammatory bowel disease (IBD) occurred in 11.2% of 27 patients. Multiple abnormalities happened in 2.5% patients. CONCLUSION: Apparently psoriasis patients seem to have a predilection for other autoimmune disorders particularly for vitiligo, diabetes mellitus, autoimmune thyroiditis, rheumatoid arthritis, and IBD. However, association between psoriasis and other autoimmune disorders at best remains tenuous for want of strong evidence. Nevertheless, screening for them will improve overall management of these patients. Cross-sectional study design and small number of study subjects remain important limitations.
32848746 Corrigendum: Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthr 2020 [This corrects the article .].
31738154 Controlled Release Gel Encompassing Curcumin Microspheres and Diclofenac Diethylamine for 2020 BACKGROUND: Diclofenac and curcumin is anticipated to have synergistic action. Hence, topical route of administration can be used in minimizing the issues with oral administration of both drugs. OBJECTIVE: This research aims at formulation of controlled release dosage form containing curcumin microspheres and diclofenac diethylamine and then incorporating it into gel formulation for treatment of inflammation associated with rheumatoid arthritis. METHODS: Curcumin microspheres were prepared, optimized and assayed. Gel containing microspheres was formulated and evaluated for physicochemical parameters like spreadability and viscosity. In vitro and ex vivo diffusion studies were carried out followed by evaluation of efficacy. Efficacy of the developed formulation was evaluated for anti-inflammatory activity. RESULTS: Particle size, Zeta potential, pH, spreadability and viscosity of optimized Batch F1 was found to be in range 0.5 µm - 5 µm,-27.9 mV, 6.2, 105 g cm/s and 7500 cps respectively. In vitro diffusion of developed gel of diclofenac diethylamine and curcumin was found to be 92.16 ± 0.0040 % in 3 h and 92.54 ± 0.0036 % in 12 h as compared to 79.57 ± 0.004 % diffusion in 2 h for marketed gel, thus showing controlled delivery of curcumin. CONCLUSION: Decreased inflammation in formulation treated group by 72.53% and 50.75% in marketed treated group was seen. Thus the formulation developed showed prolonged activity as well as better anti-inflammatory activity.
32126552 Activin A Expressed in Rheumatoid Synovial Cells Downregulates TNFα-Induced CXCL10 Expres 2020 OBJECTIVE: Activin A is known to be highly expressed in rheumatoid synovium. In the present study, we investigated the effect of inflammatory cytokines on activin A production and its role in rheumatoid inflammation using freshly prepared rheumatoid synovial cells (fresh-RSC). METHODS: Fresh-RSC from patients with rheumatoid arthritis were obtained and stimulated with multiple cytokines for activin A production. Gene expression levels of activin A and inflammatory cytokines were determined by quantitative PCR (qPCR) analysis. An enzyme-linked immunosorbent assay (ELISA) was used to measure activin A and CXCL10 in culture supernatants. The osteoclasts generated from human peripheral monocytes by RANKL stimulation were identified by tartrate-resistant acid phosphatase staining and bone resorption assay using Osteo plate. The expression levels of NFATc1 and cathepsin K, critical intracellular proteins for osteoclastogenesis, were determined by Western blotting. RESULTS: Activin A production in fresh-RSC was markedly enhanced by the synergistic effect of TGF-β1 with inflammatory cytokines, including TNFα, IL-1β, and IL-6. Activin A inhibited TNFα-induced CXCL10, an important chemoattractant for pathogen-activated T cells and monocytes of osteoclast precursors, but it did not affect the expression of inflammatory cytokines and chemokines. In addition, activin A directly inhibited the expression of NFATc1 and cathepsin K, as well as osteoclast formation in human samples. CONCLUSION: Our data indicated that TGF-β1 is involved in the expression of activin A at inflamed joints. Activin A mainly exerts an anti-inflammatory action, which prevents joint damage via the regulation of CXCL10 and osteoclastogenesis.
33163872 Acute Coronary Syndrome in a Male with Elevated Anti-Cyclic Citrullinated Peptide and no E 2020 Sep A 55-year-old male, previously known to be healthy, presented to the emergency department with a 30-minute history of chest pain radiating to the upper extremities. Vital signs were within normal limits. Four days prior to this presentation, the patient presented for acute onset of polyarthritis and morning stiffness. Significantly elevated titres of anti-cyclic citrullinated peptides (anti-CCP) were found. In the emergency department, electrocardiography showed ST segment elevations in leads V1 to V5 and aVL. Cardiac enzymes were elevated. The patient underwent cardiac catheterization. A coronary angiography revealed an ectatic proximal left anterior descending (LAD) coronary artery with critical (90-99%) stenosis at the mid segment. A drug-eluting stent was successfully inserted in the LAD without any residual stenosis. Although it is known that anti-CCP positivity is a key element in the pathogenesis of atherosclerosis in RA patients, this case report adds to the existing body of literature which demonstrates that anti-CCP positivity is an independent risk factor for development of cardiovascular events.
32895186 [Strong inflammation is essential for expression of articular cartilage-specific citrullin 2020 Aug 30 OBJECTIVE: To investigate the expression of citrullinated epitopes in articular cartilage protein and whether its expression is sufficient to induce anti-citrullinated protein antibody (ACPA) response in mice. METHODS: The experimental group was treated with different concentrations of lipopolysaccharide (LPS), heat-inactivated bacteria (Escherichia coli and Staphylococcus aureus) or specific monoclonal antibody against type â…¡ collagen to induce citrullination of articular cartilage protein, with PBS as the control. Immunohistochemistry with the monoclonal antibody ACC4 (IgG1) that specifically binds to the citrullinated epitope of cartilage protein was performed for detecting the expression of citrullinated protein, with ACC1 (IgG2a) as a positive control antibody and L243 (IgG2a) and Hy2.15 (IgG1) as the negative isotype control. In the in vivo experiment, SD rats were subjected to injection of different doses of LPS in the right knee (with PBS as the controls in the left knee), and 3 days later frozen sections were prepared for immunohistochemical detection of the expression of citrullinated protein. Models of collagen-induced arthritis (CIA) established in different mouse strains were observed for incidence and severity of CIA. Serum samples collected from these models and the sera from rheumatoid arthritis patients were examined for anti-citrullinated protein antibody, and immunohistochemistry was performed to detect the expression of citrullinated protein in the cartilage of the mouse. RESULTS: The citrullinated CII epitope-specific antibody ACC4 did not bind to articular cartilage tissues with different treatments as compared with the positive control antibody ACC1. The ACC4 antibody and the antibodies from patients with rheumatoid arthritis with high titers of anti-citrullinated protein antibody were capable of binding to the synovial tissue around the articular cartilage of the CIA. Luminex analysis showed that the anti-citrullinated protein antibody was lowly expressed in mouse serum, but the anti-type â…¡ collagen triple helix structure peptide antibody exhibited strong reactivity. CONCLUSIONS: Mild acute inflammatory response is not enough to cause citrullination of articular cartilage protein, and the expression of specific epitope requires a high-intensity inflammatory response. Inflammatory articular cartilage protein can express citrullinated epitopes in type â…¡ collagen-induced arthritis in mice, but the expression of citrullinated epitopes is not sufficient to induce an immune response to anti-citrullinated antibodies. Stronger stimulation signals are required to induce an immune response for producing anti-citrullinated protein antibodies.
32866681 Human dendritic cell-derived osteoclasts with high bone resorption capacity and T cell sti 2021 Jan Osteoclasts are typically differentiated from monocytes (Mo-OC). A subset of osteoclasts (DC-OC) that are differentiated from dendritic cells (DC) has been reported in the arthritic mice model. However, little information is available on DC-OC in humans. The present study applied both in vitro and in vivo experiments to determine the function and pathological significance of DC-OC. DC-OC were differentiated from human monocyte-derived DC and their bone resorption and antigen-presenting functions were investigated. Synovial tissue samples from patients with rheumatoid arthritis were examined for the presence and characteristics of DC-OC. DC-OC differentiated from DC in the presence of M-CSF and RANKL in vitro were demonstrated to be cathepsin K-positive and TRAP-positive multinucleated giant cells. The DC-OC showed stronger bone resorption ability than monocyte-derived osteoclast (Mo-OC) as observed with the pit formation assay. The DC-OC retained CD11c positivity and expressed costimulatory molecules, unlike Mo-OC. T-cells proliferated when co-cultured with DC-OC, but not with Mo-OC. The addition of abatacept to the cocultures reduced T-cell stimulating activity of DC-OC. Abatacept inhibited the differentiation of monocytes into Mo-OC but did not suppress the differentiation of DC into DC-OC. TRAP-positive and CD86-positive DC-OC were detected in the synovial membranes of rheumatoid arthritis patients but not in patients with osteoarthritis. Human DC-OC demonstrated T-cell stimulating activity in addition to osteolytic activity. We further observed this subset of osteoclasts in the inflammatory synovial membrane of patients with rheumatoid arthritis. Such deviations from normal bone metabolism contribute to the inflammation and bone destruction in chronic inflammatory diseases such as rheumatoid arthritis.
33424772 Mini-Review: The Contribution of Adipokines to Joint Inflammation in Inflammatory Rheumati 2020 Inflammatory rheumatic diseases (IRD) are complex disorders characterized by chronic inflammation of the joints and related skeletal structures. The most common forms of IRD are rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (axSpA) and psoriatic arthritis (PsA). Obesity is a frequent comorbidity in RA and PsA, and to a lesser extend in axial SpA. The association between obesity and IRD may be explained by the release from fat tissue of several bioactive proteins, namely adipokines. Adipokines are involved in the regulation of various processes such as lipid or glucose metabolism, but also inflammation. Adipokines are interrelated with the immune system, with both innate and adaptive immune cell connections. Several adipokines with pro-inflammatory effects have been identified such as leptin, visfatin or resistin. Conversely, adiponectin and more specifically its low molecular weight isoform, is considered to have antiinflammatory properties. In this review, we discuss the contribution of adipokines to the joint inflammation of IRD, the relation they have with immune pathways of these diseases, their links with the structural impact on peripheral joints and/or axial skeleton, and also the influence they may have on the cardiometabolic risk of IRD.
32072134 Use of antidepressants and benzodiazepine-related hypnotics before and after initiation of 2020 BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are autoimmune disorders associated with an increased risk for depression, anxiety and sleeping problems. The objective of this study was to analyze use of antidepressants and benzodiazepine-related hypnotics (BRH) in Sweden before and after first time treatment with anti-TNF and non-biological systemic (NBS) treatments among patients with the above diagnoses, and to correlate such use with that of randomly selected population controls. METHODS: Patients and dispensed drugs were identified in nationwide Swedish healthcare registers. Proportions of subjects filling prescriptions of antidepressants and BRH from 2 years before start of treatment (index-date), and 2 years after index date were assessed. Using the period -6 months to index-date as reference, prevalence rate ratios were computed for 6 months' intervals before and after index. For up to ten randomly selected population controls per patient, the same measures were calculated. RESULTS: A total of 6256 patients started anti-TNF treatment, and 13,241 NBS treatment. The mean age at index was 52.0 for the anti-TNF group and 56.1 for NBS. Use of antidepressants and BRH was similar in both treatment groups (10.4-12.8%), significantly more common than in the controls (6.6 to 7.6%). For all patients, proportions filling prescriptions for antidepressants and BRH decreased directly or soon after the index; no such changes were seen in the controls, who all showed a slow but steady increase in use over time. Starters of anti-TNF treatment did not show clearer decreases in use of psychotropics than those initiating NBS. CONCLUSIONS: Decreased rates of dispensed psychotropic drugs after the time of anti-TNF and NBS treatment initiation were seen among patients with autoimmune disorders but not population controls. This may correspond to treatment effects of anti-TNF and NBS also on psychiatric symptoms among these patients.
32660056 Rheumatoid Arthritis and CLOVES Syndrome: A Tricky Diagnosis. 2020 Jul 9 The PI3K/AKT/mTOR signaling pathway is significantly activated in rheumatoid arthritis. In addition, somatic activating mutations of the PI3K/AKT/mTOR pathway may result in PIK3CA-related overgrowth spectrum diseases, including CLOVES (Congenital Lipomatous Overgrowth, Vascular malformation, Epidermal nevi, Skeletal abnormalities/Scoliosis) syndrome. We describe the case of a young female patient, with anti-citrullinated peptide antibodies-positive rheumatoid arthritis, referred for persistent finger pain and stiffness. Examination revealed discrete macrodactyly involving two fingers, scoliosis, asymmetrical calves, venectasias, a shoulder nevus and triangular feet with a "sandal gap" between two toes. These mild dysmorphic features with early-onset and the history of surgeries for thoracic lipoma and venous malformation were strongly suggestive of CLOVES syndrome. Confirmatory mutation analysis was not performed, as blood or saliva testing is not contributive for tissue-specific localized effects in the PIK3CA-related overgrowth spectrum. Nevertheless, lack of detection of a PIK3CA mutation does not exclude the diagnosis in patients fulfilling clinical criteria. Due to the patient's wish to plan a pregnancy, therapy consisted in sulfasalazine and hydroxychloroquine, along with orthotic correction of leg length discrepancy. Overgrowth syndromes and arthritis may share common pathways. Mild macrodactyly should be differentiated from dactylitis. Diagnosing patients with minimal dysmorphic features within the PI3K-related overgrowth spectrum may help design better care strategies, in the quest for personalized medicine.
32477138 Etanercept Inhibits B Cell Differentiation by Regulating TNFRII/TRAF2/NF-κB Signaling Pat 2020 OBJECTIVE: To explore the role of B cells in rheumatoid arthritis (RA) and the potential effects and mechanisms of etanercept on B cells. METHODS: In RA patients, the levels of tumor necrosis factor-α (TNF-α) and B cell activating factor (BAFF) were detected by ELISA. The percentage of B cell subsets was measured by flow cytometry. Laboratory indicators (rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate) and clinical indicators (disease activity score in 28 joints, health assessment questionnaire score, swollen joint counts, tender joint counts) were measured. The correlation between B cell subsets and laboratory indicators or clinical indicators was analyzed. In mice, B cells proliferation was detected by CCK-8 kit. The expression of TNFRII and the percentage of B cell subsets in spleen were detected by flow cytometry. The expressions of TRAF2, p38, P-p38, p65, P-p65 in B cells were detected by WB. RESULTS: The percentage of CD19(-)CD27(+)CD138(+) plasma B cells was positively correlated with ESR or RF. Etanercept could decrease the percentage of CD19(+) total B cells, CD19(+)CD27(+) memory B cells and CD19(-)CD27(+)CD138(+) plasma B cells, reduce the levels of TNF-α, BAFF, relieve clinical and laboratory indicators in RA patients. In addition, etanercept could inhibit the proliferation of B cells, bate the differentiation of transitional B cells to mature B cells, down-regulate the expression of TNFRII, TRAF2, P-p38, P-p65 in B cells. CONCLUSION: B cells act a key role in the pathogenesis of RA. Etanercept inhibits B cells differentiation by down-regulating TNFRII/TRAF2/NF-κB signaling pathway.
32576537 Musculoskeletal Disorders due to Chikungunya Virus: A Real Experience in a Rheumatology De 2020 Jun 20 BACKGROUND: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread starts explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, the symptomatic and serological behavior, and to describe comorbidities associated to the chronic phase of the disease. METHODS: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. RESULTS: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. CONCLUSIONS: The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study.
32984127 A cross-sectional study of association of serostatus and extra-articular manifestations in 2020 Jun BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease, which mistakenly attacks the joints and induces the inflammatory changes that thicken the joints (the synovium) resulting in swelling and pain in and around the joints. It causes pain, joint deformity, and also affects the quality of life. The joint is affected symmetrically. It also can affect body systems, such as the cardiovascular, respiratory systems, or other systems, which manifest as extra-articular manifestations. Extra-articular manifestations of RA are documented less in India hence this study was undertaken to correlate RA with extra-articular manifestations as well as its relationship with serostatus in patients with extra-articular manifestations. MATERIALS AND METHODS: Sixty patients (age between 18-60 years) attending Medicine/Rheumatology outpatient department were included in the study (12 months) who fulfilled the 2010 RA classification criteria laid down by American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) for RA. All the subjects underwent a thorough history, clinical examination, and laboratory investigations. The relevant data were analyzed with appropriate statistical methods after 12 months' duration. RESULTS: Nearly 68.33% of the subjects were found to have extra-articular manifestations mostly in the age group of 31-40 years with prevalence higher in the female. In the seropositive patients, early morning stiffness (EMS) constitutes 63.82% of the total extra-articular manifestations in the patients followed by anemia (38.29%) and peripheral neuropathy (34.04%). On the other hand, in the seronegative cases, EMS (61.53%) followed by anemia (23.07), peripheral neuropathy (15.38%), and keratoconjunctivitis sicca (15.38%). Extra-articular manifestations in seropositive patients have a statistically significant relationship with the increase in the duration of the disease. CONCLUSION: Extra-articular manifestations need to be looked carefully as it is associated with more severe disease. Seropositivity and extra-articular manifestations both usually indicate that the RA is more severe and may affect the quality of life.
32089102 Dry eye in rheumatoid arthritis: relation to disease activity. 2020 Jun The aim of this study was to find the correlation between severity of dry eye and rheumatoid arthritis (RA) disease activity. Forty- two RA patients with dry eye were recruited from Rheumatology Outpatient Clinic in Minia University Hospital. Assessment of RA disease activity was performed using disease activity score (DAS-28). Ocular tests include Schirmer test I, tear film break up time (TBUT) and ocular staining score (OSS) was performed by ophthalmologist to find evidence of ocular dryness. Erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), anti SSA/Ro and anti SSB/La was also tested. Patients with severe dry (OSS ≥ 3) underwent minor salivary gland biopsy (MSGB) as suspected to have secondary Sjögren's syndrome (SS). Of 42 RA patients, 30 had definite dry eye. DAS-28 did not show significant correlation with any of ocular tests for dryness while the duration of RA was significantly positively correlated with Schirmer test and OSS. The biopsy results of RA patients with severe dry eye show no evidence of SS. The severity of dry eye is not correlated with activity of RA but with its duration.
32256787 TlR2 and TlR4 are involved in the treatment of rheumatoid arthritis synovial fibroblasts w 2020 Apr Asarinin is one of the main active chemical components isolated from Xixin, a Chinese medicine. To investigate the role of asarinin in rheumatoid arthritis (RA), the present study investigated the effect of an asarinin-medicated serum on human fibroblast-like synoviocytes in vitro. An asarinin-medicated serum was generated and analyzed by high-performance liquid chromatography. Fibroblast-like synoviocytes were isolated from patients with osteoarthritis and RA. The third generation of the rheumatoid synoviocytes was used in the experimental research and the third generation of osteoarthritic synoviocytes was used as control cells. Trypan blue staining was performed to detect the viability of RA synovial fibroblasts (RASFs). ELISA, reverse transcription-quantitative (RT-q) PCR and western blotting were also performed to detect the expression of various cytokines. Additionally, RT-qPCR was employed to detect Toll-like receptor (TLR) 2 and TLR4. The results revealed that medicated asarinin serum inhibited the viability of RASFs in a dose- and time-dependent manner. The serum also suppressed the expression of interleukin (IL)-17A, tumor necrosis factor-α, interferon-γ, IL-6, TLR2 and TLR4. The inhibitory effect of asarinin drug serum on RASFs may be achieved by inhibition of T helper cell (T(h))1/T(h)17 cytokines through suppression of TLR2 and TLR4.
32560528 A Systematic Review Comparing Experimental Design of Animal and Human Methotrexate Efficac 2020 Jun 17 Increased awareness and understanding of current practices in translational research is required for informed decision making in drug development. This paper describes a systematic review of methotrexate for rheumatoid arthritis, comparing trial design between 147 animal and 512 human studies. Animal studies generally included fewer subjects than human studies, and less frequently reported randomisation and blinding. In relation to life span, study duration was comparable for animals and humans, but included animals were younger than included humans. Animal studies often comprised males only (61%), human studies always included females (98% included both sexes). Power calculations were poorly reported in both samples. Analyses of human studies more frequently comprised Chi-square tests, those of animal studies more frequently reported analyses of variance. Administration route was more variable, and more frequently reported in animal than human studies. Erythrocyte sedimentation rate and c-reactive protein were analysed more frequently in human than in animal studies. To conclude, experimental designs for animal and human studies are not optimally aligned. However, methotrexate is effective in treating rheumatoid arthritis in animal models and humans. Further evaluation of the available evidence in other research fields is needed to increase the understanding of translational success before we can optimise translational strategies.
32533534 Intestinal microbiota and juvenile idiopathic arthritis: current understanding and future 2021 Feb BACKGROUND: Juvenile idiopathic arthritis (JIA) characterized by arthritis of unknown origin is the most common childhood chronic rheumatic disease, caused by both host genetic factors and environmental triggers. Recent evidence has mounted to focus on the intestinal microbiota, a potentially recognized set of environmental triggers affecting JIA development. Here we offer an overview of recently published animal and human studies that support the impact of intestinal microbiota in JIA. DATA SOURCES: We searched PubMed for animal and human studies publications with the search terms "intestinal microbiota or gut microbiota" and "juvenile idiopathic arthritis or juvenile chronic arthritis or juvenile rheumatoid arthritis or childhood rheumatoid arthritis or pediatric rheumatoid arthritis". RESULTS: Several comparative studies have demonstrated that intestinal microbial alterations might be triggers in disease pathogenesis. Alternatively, a slice of studies has suggested environmental triggers in early life might disrupt intestinal microbial colonization, including cesarean section, formula feeding, and antibiotic exposure. Aberrant intestinal microbiota may influence the development of JIA by mediating host immune programming and by altering mucosal permeability. CONCLUSIONS: Specific microbial factors may contribute to the pathogenesis of JIA. Intensive studies, however, are warranted to investigate the causality between intestinal dysbiosis and JIA and the mechanisms behind these epidemiologic relationships. Studies are also needed to design the best interventional administrations to restore balanced intestinal microbial communities.
33245555 Update on the Safety Profile of Tofacitinib in Rheumatoid Arthritis from Clinical Trials t 2021 Mar Tofacitinib is approved for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who do not respond adequately or are intolerant to one or more disease-modifying anti-rheumatic drugs. The tofacitinib RA clinical development program included randomized controlled trials of 6-24-month duration and long-term extension studies with > 7061 patients and 22,875 patient-years of exposure. To date, there are no data from other randomized studies in patients with cardiovascular risk factors comparing the long-term safety of a JAK inhibitor versus an anti-TNF. Real-world studies are necessary to complete the body of evidence supporting the effectiveness and safety of a therapeutic agent. In the case of tofacitinib, real-world data derive from health insurance claims databases, registries (US Corrona Registry, Swiss Registry, and others), national pharmacovigilance programs, and hospital databases (case series). The present article provides complete and up-to-date information on the safety profile of tofacitinib in RA, from clinical trials to real-world studies. Tofacitinib has demonstrated a consistent safety profile during up to 9.5 years of experience in randomized controlled trials and long-term extension studies. Real-world evidence has not added new safety issues with respect to those found in the clinical program. In general, the safety profile of tofacitinib is consistent with that of biologic disease-modifying anti-rheumatic drugs, with an increased risk of herpes zoster that seems to be a class effect of Janus kinase inhibitors. The continuous follow-up of therapeutic agents to treat rheumatoid arthritis is needed to adequately establish the safety profile for new mechanisms of action and potential risks associated with their longer term use.