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ID PMID Title PublicationDate abstract
34838694 Elucidation of the anti-inflammatory mechanism of Er Miao San by integrative approach of n 2022 Jan Traditional Chinese medicine (TCM) has been long time used in China and gains ever-increasing worldwide acceptance. Er Miao San (EMS), a TCM formula, has been extensively used to treat inflammatory diseases, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the underlying mechanisms of EMS in treating human rheumatoid arthritis (RA) and other inflammatory conditions. Quercetin, wogonin and rutaecarpine were probably the main active compounds of EMS in RA treatment as they affected the most RA-related targets, and TNF-α, IL-6 and IL-1β were considered to be the core target proteins. The main compounds in EMS bound to these core proteins, which was further confirmed by molecular docking and bio-layer interferometry (BLI) analysis. Moreover, the potential molecular mechanisms of EMS predicted from network pharmacology analysis, were validated in vivo and in vitro experiments. EMS was found to inhibit the production of NO, TNF-α and IL-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells; reduce xylene-induced mouse ear edema; and decrease the incidence of carrageenan-induced rat paw edema. The carrageenan-induced up-regulation of TNF-α, IL-6 and IL-1β mRNA expression in rat paws was down-regulated by EMS, consistent with the network pharmacology results. This study provides evidence that EMS plays a critical role in anti-inflammation via suppressing inflammatory cytokines, indicating that EMS is a candidate herbal drug for further investigation in treating inflammatory and arthritic conditions.
34463054 Association of Bone Erosions and Osteophytes With Systemic Bone Involvement on High-Resolu 2022 Mar OBJECTIVE: To evaluate premenopausal women with longstanding rheumatoid arthritis (RA) for potential associations between parameters of localized bone involvement and parameters of systemic bone involvement in the affected joints. METHODS: Eighty consecutively evaluated premenopausal women with RA were included in the study, along with 160 healthy female control subjects who were matched to the patients by age and body mass index. Volumetric bone mineral density (vBMD), bone microarchitecture, and finite elements of biomechanical bone strength (bone stiffness and estimated failure load) at the distal radius and distal tibia were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with RA compared to healthy controls. In addition, in patients with RA, localized bone involvement in the metacarpophalangeal and proximal interphalangeal joints was analyzed by HR-pQCT, to identify bone erosions and osteophytes. RESULTS: Among the 80 premenopausal women with longstanding RA, the mean ± SD age was 39.4 ± 6.7 years and mean ± SD disease duration was 9.8 ± 5.3 years. Trabecular and cortical bone parameters and bone strength at the distal radius and distal tibia were all impaired in patients with RA compared to healthy controls (each P < 0.05). In total, 75% of RA patients had evidence of bone erosions, and 41.3% of RA patients had detectable osteophytes on HR-pQCT. RA patients with bone erosions, as compared to RA patients without bone erosions, had lower cortical vBMD (at the distal radius, mean ± SD 980 ± 72 mg HA/cm(3) versus 1,021 ± 47 mg HA/cm(3) [P = 0.03]; at the distal tibia, 979 ± 47 mg HA/cm(3) versus 1,003 ± 34 mg HA/cm(3) [P = 0.04]) and higher cortical bone porosity (at the distal radius, mean ± SD 2.8 ± 2.5% versus 1.8 ± 1.6% [P = 0.04]; at the distal tibia, 3.7 ± 1.6% versus 2.7 ± 1.6% [P = 0.01]). In patients with RA, osteophyte volume at the distal radius was positively correlated with trabecular vBMD (r = 0.392, P = 0.02), trabecular number (r = 0.381, P = 0.03), and trabecular stiffness (r = 0.411, P = 0.02), and negatively correlated with trabecular separation (r = -0.364, P = 0.04), as determined by Pearson's or Spearman's correlation test. CONCLUSION: The findings show that premenopausal women with longstanding RA have systemic bone fragility at peripheral joint sites. Moreover, the presence of bone erosions is mainly associated with cortical bone fragility at the distal radius and tibia, and presence of osteophytes is associated with repair of trabecular bone at the distal radius.
34622969 Switching between reference adalimumab and biosimilars in chronic immune-mediated inflamma 2022 Feb AIMS: Adalimumab is a biological therapy used to treat different chronic inflammatory diseases. At present, there is an increasing number of adalimumab biosimilars. To assume the acceptability of interchangeability between reference adalimumab and biosimilars, there should be evidence about efficacy and safety of this switching. Regulation of this practice falls under the authority of individual European Union Member States. The aim of this study is to systematically review the evidence on the efficacy, safety and immunogenicity of switching between reference adalimumab and biosimilars in different chronic immune-mediated inflammatory diseases. METHODS: Studies presenting data about switching between reference adalimumab and biosimilars were identified by sensitive search strategies in Medline and EMBASE from 1 January 2004 to 30 June 2021. RESULTS: A total of 471 references were obtained and 21 finally included in the analysis (total number of patients switching: 2802). Eight different adalimumab biosimilars were tested after receiving reference adalimumab. Eight articles included rheumatoid arthritis (RA), one miscellaneous rheumatic disease, six psoriasis (PSO) and six inflammatory bowel disease (IBD) patients. Overall, the efficacy results in the switching groups were comparable to those obtained in the arms of continuous biosimilar and continuous reference adalimumab. There were no significant differences in treatment emergent adverse events, anti-drug or neutralising antibodies among the three groups. CONCLUSIONS: Switching between reference adalimumab and biosimilars has no impact on efficacy, safety and immunogenicity in patients with RA, PSO and IBD. This finding was consistent for the different adalimumab biosimilars analysed. These conclusions could probably be extended to other rheumatic diseases such as psoriatic arthritis and ankylosing spondylitis.
34819392 CD8(+) T Cells Expressing an HLA-DR1 Chimeric Antigen Receptor Target Autoimmune CD4(+) T 2022 Jan 1 Ag-specific immunotherapy is a long-term goal for the treatment of autoimmune diseases; however developing a means of therapeutically targeting autoimmune T cells in an Ag-specific manner has been difficult. Through the engineering of an HLA-DR1 chimeric Ag receptor (CAR), we have produced CD8(+) CAR T cells that target CD4(+) T cells in an Ag-specific manner and tested their ability to inhibit the development of autoimmune arthritis in a mouse model. The DR1 CAR molecule was engineered to contain CD3ζ activation and CD28 signaling domains and a covalently linked autoantigenic peptide from type II collagen (CII; DR1-CII) to provide specificity for targeting the autoimmune T cells. Stimulation of the DR1-CII CAR T cells by an anti-DR Ab induced cytokine production, indicating that the DR1-CAR functions as a chimeric molecule. In vitro CTL assays using cloned CD4(+) T cells as target cells demonstrated that the DR1-CII CAR T cells efficiently recognize and kill CD4(+) T cells that are specific for the CII autoantigen. The CTL function was highly specific, as no killing was observed using DR1-restricted CD4(+) T cells that recognize other Ags. When B6.DR1 mice, in which autoimmune arthritis had been induced, were treated with the DR1-CII CAR T cells, the CII-specific autoimmune CD4(+) T cell response was significantly decreased, autoantibody production was suppressed, and the incidence and severity of the autoimmune arthritis was diminished. These data demonstrate that HLA-DR CAR T cells have the potential to provide a highly specific therapeutic approach for the treatment of autoimmune disease.
34128794 Adherence to and patient's knowledge of self-management of subcutaneous biologic therapy i 2022 May OBJECTIVES: Non-adherence to biologic therapy is an issue in chronic inflammatory rheumatic diseases (CIRDs) and might be related to poor patient knowledge of the risk of these therapies. Our aim here was to evaluate the level of patient adherence to and knowledge of self-care safety skills for biologic therapy. METHODS: This was a multicentre, cross-sectional study in which out-patients visited an office- or hospital-based rheumatologist. All the patients received subcutaneous biologic therapy for CIRDs. We collected data on: 1. the level of CIRD patient adherence to current subcutaneous biologic therapy using both the self-administered Compliance Questionnaire Rheumatology 5 items (CQR5) and a simple adherence question; 2. patients' knowledge of self-management of biologic therapy by the self-administered BIOSECURE questionnaire; 3. sources of information related to biologic therapy. RESULTS: In all, 285 patients (rheumatoid arthritis, n=103; spondyloarthritis, n=153; psoriatic arthritis, n=25) were enrolled by 19 rheumatologists. The mean (SD) biologic therapy duration was 5.9 (4.9) years. Adherence to the current biologic therapy was high (79.3% and 57.5% according to the CQR5 questionnaire and the adherence question, respectively). Level of knowledge of self-care safety skills (median BIOSECURE score 71) was in the acceptable range. Level of adherence and level of knowledge of self-care safety skills for biologic therapy were not associated. Patients declared that the main sources of information were their rheumatologist (92.6%) and the rheumatology team (30.5%). CONCLUSIONS: According to the patients' estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).
35083342 Peptidylarginine Deiminase 2 in Murine Antiviral and Autoimmune Antibody Responses. 2022 The peptidylarginine deiminases (PADs) and the citrullinated proteins that they generate have key roles in innate immunity and rheumatoid arthritis, an inflammatory arthritis with antibodies that target citrullinated proteins. However, the importance of PADs, particularly PAD2, in the adaptive immune response, both normal and pathogenic, is newly emerging. In this study, we evaluated a requirement for PAD2 in the antibody response in collagen-induced arthritis (CIA), a T and B cell-driven murine model of rheumatoid arthritis, and in the protective antibody response to murine influenza infection. Using PAD2(-/-) and PAD2(+/+) mice on the DBA/1J background, we found that PAD2 is required for maximal anti-collagen antibody levels, but not collagen-specific plasma cell numbers, T cell activation or polarization, or arthritis severity in CIA. Also, we found that PAD2 is required not just for normal levels of persistent hemagglutination inhibiting antibodies but also for full protection from lethal influenza rechallenge. Together, these data provide evidence for a novel modest requirement for PAD2 in a normal antiviral antibody response and in an abnormal autoantibody response in inflammatory arthritis.
34750103 Perceptions and experiences of individuals at-risk of rheumatoid arthritis (RA) knowing ab 2022 Feb OBJECTIVES: There is increasing interest in identifying individuals at-risk of rheumatoid arthritis (RA) and initiating early treatment to prevent or delay the onset of arthritis. We aimed to describe the perceptions and experiences of at-risk individuals and to inform the conduct of clinical trials and studies, and clinical practice. METHODS: A systematic review and thematic synthesis of qualitative studies was conducted. Two review authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist and assessed confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in Evidence from Reviews of Qualitative Research approach. RESULTS: Seven studies involving 115 individuals at-risk of developing RA were included. Three major themes (seven subthemes) were identified: understanding the risk of developing RA (knowledge of RA and identification of potential risk factors); preventive interventions to reduce the risk of developing RA (understanding the value and role of preventive interventions, and engagement with preventive interventions); and perceptions of predictive testing for RA (benefits of predictive testing, decision to undertake predictive testing and concerns about predictive testing). Moderate confidence in most review findings was evident. CONCLUSION: While there are clear benefits in informing individuals at-risk of RA about their risk following predictive testing and offering preventive treatment, there are potential barriers to engagement, intensified by the burden of uncertainty. Identification of the optimum approaches for presenting risk information, including the risks and benefits of engaging with preventive interventions, is urgently needed to support individuals at-risk of RA in their decision making. PROSPERO REGISTRATION NUMBER: CRD42021236034.
35548080 Immunogenicity of Inactivated SARS-CoV-2 Vaccines in Patients With Rheumatoid Arthritis: A 2022 OBJECTIVES: Attenuated humoral response to mRNA SARS-CoV-2 vaccines has been reported in some patients with autoimmune disease, e.g., rheumatoid arthritis (RA). However, data of immune responses to inactivated SARS-CoV-2 vaccine in the RA population are still unknown. Herein, the safety and immunogenicity of inactivated SARS-CoV-2 vaccines in RA patients were analyzed. METHODS: Seventy five RA patients and 26 healthy controls (HC) were respectively recruited from Yunnan Provincial Hospital of Traditional Chinese Medicine and the community in Kunming city. Neutralizing Antibody (NAb) Test ELISA kit was used to measure the percentage of inhibition. AKA (anti-keratin antibody) positivity was detected using indirect immunofluorescence. Rheumatoid factor (RF)-IgA was detected by ELISA. RF-IgG, RF-IgM, and anti-cyclic citrullinated peptide (CCP) antibodies were measured by chemiluminescence. ESR (erythrocyte sedimentation rate) was detected by ESR analyzer. C-RP (c-reactive protein) was detected by immunoturbidimetry. NEUT% (percentage of neutrophils) and LYMPH% (percentage of percentage) were calculated by a calculation method. RESULTS: Compared with the HC group, the percentage of inhibition was significantly lower in RA patients receiving two doses of vaccines. Vaccines-induced percentage of inhibition was the lowest in RA patients who had not been vaccinated. In total 80.77% of the HC group had a percentage of inhibition ≧20%, compared with 45.24% of vaccinated RA patients and 6.06% of unvaccinated RA patients. Spearman correlation analysis revealed that antibody responses to SARS-CoV-2 did not differ between RA patients according to their age and disease duration. Furthermore, the results showed that no correlation was found between the percentage of inhibition and indices for RA, including RF-IgA, IgG, IgM; anti-CCP antibody; ESR; C-RP; NEUT% and LYMPH%. CONCLUSION: Our study showed inactivated vaccine-induced SARS-COV-2 antibody responses differ in RA patients and healthy subjects, emphasizing the importance of a third or fourth vaccination in RA patients.
34599798 Time in remission as an alternative outcome measure for rheumatoid arthritis: a 10-year pr 2022 May 30 OBJECTIVE: Achieving targeted disease activity (DA) is the primary therapeutic strategy in RA. Point measurements of DA are done at out-patient visits, however true DA between visits remains unobserved. This study sought to describe and validate a new outcome measure, i.e. time in remission (TIR). METHODS: Patients were enrolled in the Czech ATTRA-RA registry. TIR was calculated using linear interpolation of the DAS28-ESR determined at outpatient visits. Correlation coefficients were computed between TIR and DAS28-CRP, HAQ, Simple Disease Activity Index (SDAI), patient global assessment (PGA) and physician global assessment (PhGA). Using logistic regression, TIR was used as a predictor of remission (SDAI ≤3.3) and non-disability (HAQ <0.5). The predictive value of TIR was compared with point and sustained remission using the cross-validated area under receiver-operating curves. RESULTS: Since 2010, 2618 RA patients started anti-TNF therapy and were followed until 2020 or until treatment discontinuation. During the first 6 months of therapy, 56% of patients had no remission (TIR = 0), and 22% of patients reached sustained remission (TIR = 1), while 22% of patients had point remissions with 0 < TIR < 1. EULAR good responders and moderate/non-responders spent 64 ± 42% and 6 ± 18% of time in remission, respectively. The mean TIR grew during the follow-up and was correlated with DAS28-CRP, SDAI, HAQ, PGA, and PhGA (P < 0.0001). TIR at 3 and 6 months predicted remission (SDAI ≤3.3) and non-disability (HAQ <0.5) at 13 and 19 months better than point or sustained remission. CONCLUSIONS: TIR is an intuitive way of estimating unobserved DA between scheduled visits; its calculation only requires two consecutive DA values (https://www.medevio.cz/tir-calculator/). TIR is a valid predictor of RA outcomes.
35148199 SLAMF7 engagement superactivates macrophages in acute and chronic inflammation. 2022 Feb 11 Macrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a superactivated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression and engaging SLAMF7 drove a strong wave of inflammatory cytokine expression. Induction of TNF-α after SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients but also in gut macrophages from patients with active Crohn's disease and in lung macrophages from patients with severe COVID-19. This suggests a central role for SLAMF7 in macrophage superactivation with broad implications in human disease pathology.
34382085 The response to TNF blockers depending on their comparator in rheumatoid arthritis clinica 2022 Feb 2 OBJECTIVE: To compare the effect of the biological reference agents (infliximab, etanercept, adalimumab) in RA in pivotal superiority placebo-controlled trials (reference agent vs placebo) vs their effect in equivalence active comparator-controlled trials (reference agent vs biosimilar). METHODS: The PubMed, EMBASE and Cochrane databases were searched for randomized, double-blind, controlled trials up to March 2020 comparing a biological reference agent vs placebo or biosimilar. The study assessed the ACR 20/50/70 responses of the reference agent in these groups (Reference-pbo and Reference-bs, respectively). The effect of the reference agent in both groups was estimated with 95% CI, pooled using random-effects models and then compared using a meta-regression model. RESULTS: We included 31 trials. The main characteristics of the population (disease duration and activity, % seropositivity and methotrexate dose) of the population in both groups were similar. The meta-analysis found a better ACR20 response to the biological originator in the Reference-bs group with a global rate of 70% (95% CI, 66, 74) compared with 59% (95% CI, 55, 62) in the reference-pbo group (P =0.001). A significant difference was also found for ACR 50 [44% (95% CI, 39, 50) vs 35% (95% CI, 31, 39), respectively, P <0.01]. CONCLUSION: The effect of the reference biologic agent was better when compared with an active drug to a placebo. This could be linked to an increased placebo effect in active comparator-controlled studies or a nocebo effect in placebo-controlled studies. This effect can be called the lessebo effect.
35325438 A Developer's Perspective on Clinical Evidence and Benefits for Rituximab Biosimilar Uptak 2022 Apr To date, four rituximab biosimilars have received regulatory approval from the European Medicines Agency and/or US Food and Drug Administration. CT-P10 was the first rituximab biosimilar to be approved by each agency, in 2017 and 2018, respectively. Regulatory approval of CT-P10 followed demonstration of pharmacokinetic equivalence to the reference product in a phase I study in patients with rheumatoid arthritis. Phase III pivotal studies of CT-P10 subsequently demonstrated equivalence or non-inferiority of pharmacokinetics and efficacy between CT-P10 and reference rituximab in patients with rheumatoid arthritis, advanced-stage follicular lymphoma, and low-tumour-burden follicular lymphoma. Almost 5 years after its initial regulatory approval, significant real-world experience has accumulated with CT-P10 use, particularly in diffuse large B-cell lymphoma, one of the indications approved by extrapolation. This article summarises the pivotal data underlying regulatory approval for the four licensed rituximab biosimilars, before focusing on real-world data gathered with CT-P10. These data provide further support for the safety and effectiveness of CT-P10 and should boost healthcare professional and patient confidence in its use. Pharmacoeconomic analyses support the potential healthcare system cost savings offered by rituximab biosimilar uptake, which could lead to improved patient access to biologic treatments. Opportunities arising from biosimilar uptake extend further, potentially enabling innovative investigator-led research and therapeutic advances.
34941617 Assessment of the Sources of Information by Patients With Rheumatic Diseases. 2022 Jan 1 OBJECTIVE: The aim of this study was to ascertain the frequency of use, search intent (SI), level of accessibility, and degree of reliability of sources of information (SOIs) in rheumatology. METHODS: A survey among adult outpatients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and spondyloarthritis was conducted. They were asked if they had procured information from 12 selected SOIs during the past year. Search intent was defined as the source they would like to consult. Accessibility and reliability were assessed through 0-to-10 scales (minimum and maximum, respectively). RESULTS: Four hundred two patients were surveyed. They had consulted a median of 3 SOIs (interquartile range, 2-6) but described a higher SI: median of 5 SOIs (interquartile range 3-8); p = 0.001.The most consulted SOIs were the physician (83%), other patients (45%), and Facebook (36%). The main differences between SI and the searches actually performed were observed in community lectures by health care professionals (49%), scientific societies (48%), and associations of patients (27%); p < 0.001. These 3 sources showed low level of accessibility. Facebook, press, radio, and YouTube were the least reliable sources. CONCLUSIONS: Patients consulted a median of 3 SOIs but reported a significantly higher SI. Although patients demand more information, the request is leveled at SOIs with difficult accessibility but high reliability.
34839415 Comparing longitudinal patient-reported outcome measures between Swedish patients with rec 2022 May The onset of rheumatic disease affects each patient differently and may impact quality of life with progression. We investigated the relationship between patient-reported outcome measure (PROM) scores and organ damage in patients with recent-onset systemic lupus erythematosus (SLE) and those with early rheumatoid arthritis (RA). Patients with recent-onset SLE without prior organ damage from the Clinical Lupus Register in Northeastern Gothia and patients with early RA from the observational 2nd Timely Interventions in Early RA study, Sweden, were included. Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI) was used to assess organ damage. PROM (visual analog scale [VAS]: pain, fatigue, well-being, Health Assessment Questionnaire, and EQ-5D-3L) scores were captured at months 0, 6, 12, 24, 36, 48, and 60 after diagnosis. Statistical tests included Pearson correlation coefficients and t-tests. Forty-one patients with recent-onset SLE and 522 with early RA were included. Numerical differences were seen in age and sex. PROMs were worse for patients with RA versus SLE but improved by month 6 following diagnosis, while SLE PROMs remained stable. The incidence of organ damage in SLE was 13.6 per 100 patient-years. SDI significantly correlated with EQ-5D-3L (- 0.48, P = 0.003), VAS fatigue (0.44, P = 0.009), and well-being (0.41, P = 0.01) at month 24. As illustrated, the complexity of disease burden in patients with SLE is clear and may result from disease-related multiorgan system effects and slower symptom resolution compared with RA. This underscores the need for improved multiprofessional interventions to manage all aspects of SLE. Key Points • We observed an evident discrepancy in patient-reported outcome measures (PROMs) between patients with recent-onset SLE and early RA. • Despite differences in PROMs between patients with recent-onset SLE and early RA, both groups had prominent self-reported disability during the study period. • PROM scores for patients with RA were generally worse than those with SLE but improved by month 6, whereas PROM scores for patients with SLE remained stable over time. • Our findings underline the need of new therapeutic options and interventions for SLE disease management, including pharmacologic and multiprofessional aspects.
35020867 miR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from p 2022 Apr 4 MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.
35034771 Applying Early Intervention Strategies to Autoimmune Skin Diseases. Is the Window of Oppor 2022 Mar Many inflammatory skin diseases exhibit a chronic course with unsatisfactory long-term outcomes. Insights into early intervention approaches in other autoimmune contexts could improve the trajectory of lifelong diseases in terms of sustained remission or minimal disease activity, reduced requirement for therapy and medical resource use, and improved QoL. In both rheumatoid arthritis (RA) and psoriatic arthritis (PsA), we have learned that the timing and intensity of early interventions can influence later outcomes. Investigation into early RA, PsA, and systemic lupus erythematosus has shown that the optimal window of opportunity may even extend into asymptomatic preclinical phases of diseases. Notably, early and preclinical diseases may have pathogenic mechanisms and therapeutic targets that differ from those of the established disease. In this paper, we review the literature on these insights and discuss how similar research and therapeutic strategies may be investigated in cutaneous autoimmunity. We highlight the contribution of skin-resident cells to diseases that were previously thought to be initiated in the primary and secondary lymphoid organs of the immune system. We focus on two dermato‒rheumatology conditions-lupus and psoriasis-which share the commonality that effective early cutaneous disease therapy may have far-reaching implications on abrogating potentially severe systemic disease.
34581890 Perceptions and behaviours related to COVID-19 in patients with rheumatoid arthritis: a cr 2022 Jan OBJECTIVES: To study the perceptions and behavioural changes related to the coronavirus disease 2019 (COVID-19) in patients with rheumatoid arthritis (RA) and determine their associations with patient characteristics, such as health literacy. METHODS: This cross-sectional study was conducted from September to November of 2020 and included 400 outpatients with RA aged 18 and above. We measured self-reported perceptions as outcomes, such as awareness, knowledge and behaviours related to COVID-19. Health literacy and other characteristics as exposures were investigated using self-report questionnaires and electronic health records. To analyse the association between patient factors and the outcomes, multivariable linear and logistic regression models were performed. RESULTS: In total, 365 patients completed the survey. More than half (51%) of patients reported that they were 'very worried' about possible infection with COVID-19, whereas over 80% believed the possibility of getting COVID-19 was low. In the multivariable analyses, patients with low health literacy had limited knowledge about COVID-19 and did not change daily routines and perform preventive measures. CONCLUSIONS: In this pandemic, healthcare providers may need to be aware of more vulnerable individuals and share COVID-19 related information promptly and effectively with their patients. Key Points • This cross-sectional study aimed to investigate the perceptions and behavioural changes related to COVID-19 in patients with RA. • All patients were aware of COVID-19 and most of them worried about getting infected. • Health literacy, age, sex, disease activity and rheumatic drugs were associated with perceptions and behaviours related to COVID-19.
35234168 miR-205-5p in exosomes divided from chondrogenic mesenchymal stem cells alleviated rheumat 2022 Mar 1 OBJECTIVE: To explore the role and mechanism of chondrogenic bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on Rheumatoid arthritis (RA). METHODS: The chondrogenesis of BMSCs was induced by chondrogenic medium. Exosomes from BMSCs and chondrogenic BMSCs were isolated and characterized by transmission electron microscope (TEM), laser particle size analyzer and western blot. ELISA was used to analyze the expression levels of pro-inflammatory cytokines and matrix metalloproteinases (MMPs). Western bolt was performed to assess MAPK and NF-κB pathways expression. The inflammation score and the pathological damage of RA mice were evaluated. Luciferase reporter assay and RIP were carried out to examine the relationship between microRNA-205-5p (miR-205-5p) and mouse double minute 2 (MDM2). RESULTS: Chondrogenic BMSCs-derived exosomes suppressed pro-inflammatory cytokines, MMPs and MAPK and NF-κB pathways in RA-FLSs. miR-205-5p had a high expression in chondrogenic BMSCs-derived exosomes. Functionally, exosomal miR-205-5p also played the anti-inflammation effects. Besides, MDM2 was a direct target of miR-205-5p. Additionally, chondrogenic BMSCs-secreted exosomal miR-205-5p suppressed the inflammation score, joint destruction, and inflammatory response in collagen-induced arthritis (CIA) mice through MDM2. CONCLUSION: Chondrogenic BMSCs-derived exosomal miR-205-5p suppressed inflammatory response, MAPK and NF-κB pathways through MDM2 in RA, indicating exosomal miR-205-5p might be a potential target for RA treatment.
35410356 Adenosine inhibits TNFα-induced MMP-3 production in MH7A rheumatoid arthritis synoviocyte 2022 Apr 11 Adenosine causes the anti-inflammatory effect of MTX; however, the contributions of synoviocyte adenosine receptors (AdoRs) are unknown, and matrix metalloproteinase 3 (MMP-3) is released by fibroblast-like synoviocytes in response to inflammatory signaling. To understand the mechanism of the clinical observation that the matrix proteinase-3 concentration of patients with rheumatoid arthritis treated successfully with methotrexate does not usually normalize, we investigated the effects of A(2A) AdoR activation and inhibition on tumor necrosis factor-alpha (TNFα)-induced MMP-3 release by MH7A human rheumatoid synovial cells. MH7A cells constitutively expressed membrane-associated A(2A) AdoRs, and HENECA enhanced intracellular cAMP. Stimulation with TNFα markedly enhanced release of MMP-3 from MH7A cells, whereas HENECA partially and dose-dependently inhibited TNFα-evoked MMP-3 release. Similarly, dbcAMP partially inhibited TNFα-induced MMP-3 release. Pretreatment with ZM241385 reversed the inhibitory effects of HENECA. Further, TNFα induced p38 MAPK and ATF-2 phosphorylation, whereas HENECA suppressed p38 MAPK and ATF-2 phosphorylation. We concluded that adenosine signaling via A(2A) AdoRs, adenylyl cyclase, and cAMP reduces TNFα-induced MMP-3 production by interfering with p38 MAPK/ATF-2 activity. Activation of A(2A) AdoR signaling alone using HENECA did not reduce TNFα-induced MMP-3 production to the basal levels, which may explain why MTX usually decreases but does not eliminate serum MMP-3.
35259710 NK cells - Dr. Jekyll and Mr. Hyde in autoimmune rheumatic diseases. 2022 Jun Natural killer (NK) cells belong to innate immune system that are large granular lymphocytes differentiating from the common lymphoid progenitors. These cells were first identified by their functional response against tumor cells and virus-infected cells. That notwithstanding, NK cells are able to affect both adaptive and innate immune arms and modulate a wide range of immune cells. As a consequence, NK cells are capable of bridging between the innate and adaptive immune responses. The effector cytokines as well as direct cell-cell cytotoxicity by NK cells have been shown to be involved in the regulation of the immune responses and might participate in the etiopathogenesis of several disorders, particularly autoimmune rheumatic diseases (AIRDs), such as Ankylosing spondylitis (AS), Rheumatoid arthritis (RA), Systemic lupus erythematosus (SLE), Behcet's disease (BD), Systemic sclerosis (SSc), and psoriasis. Nonetheless, NK cells demonstrate both harmful and protective functions during autoimmune diseases pathogenesis based on the subset of NK cell as well as disease microenvironment and disease phase or genetic/environmental stimuli. Here in this review, we intend to go through the recent findings in the etiology and pathogenesis of AIRDs and discuss about their clinical potential to be utilized as targets for the sake of therapy in the context of such disorders.