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ID PMID Title PublicationDate abstract
31903822 Response to tocilizumab and work productivity in patients with rheumatoid arthritis: 2-yea 2021 Jan OBJECTIVES: We evaluated long-term control of rheumatoid arthritis (RA) in Japanese paid workers (PWs) and house workers (HWs) treated with subcutaneous tocilizumab (TCZ-SC) and explored factors affecting response to TCZ-SC regarding work productivity. METHODS: This study collected data from patients with RA in the TCZ-SC +/- conventional synthetic disease-modifying antirheumatic drugs group. Factors affecting the response to tocilizumab regarding work productivity were explored using logistic regression. Differences in quality-adjusted life years (QALYs) between with/without response were analysed by a linear regression. RESULTS: Data were analysed for 357/360 patients. Patients with a ≥ 75% improvement in activity impairment (AI) were considered responders. EuroQol-5 Dimension (EQ-5D), six-item Kessler psychological distress scale score (K6), Health Assessment Questionnaire Disability Index (HAQ-DI), and the patient's disease global health by visual analogue scale were significant contributors to TCZ-SC response based on improvements in AI. Work Functioning Impairment Scale, presenteeism, EQ-5D, K6, and HAQ-DI significantly contributed to the improvement of overall work impairment in PWs. Shorter disease duration also was related to TCZ-SC response based on AI improvements. Responders had significantly larger mean QALYs than non-responders (difference = 0.2614; p < .001). CONCLUSIONS: These real-world clinical data support long-term work productivity control with TCZ-SC for biologic-naïve HWs and PWs with RA.
34344436 Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients? 2021 Aug 3 OBJECTIVES: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment. METHODS: We assessed the aortic wall inflammation of RA patients using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR). RESULTS: A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUV(max)) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUV(max) and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032). CONCLUSION: The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.
32221774 Cancer in adult patients with inflammatory arthritis is associated with high ascending aor 2021 Jan Inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are associated with both cancer and cardiovascular (CV) adverse events. Cancer and CV abnormalities have coincident etiologic and pathophysiologic pathways in RA/PsA/AS patients. However, a comprehensive evaluation of CV system has never been performed in these patients in relation to the presence of cancer. This study was designed to assess the possible relationships between CV abnormalities and cancer among RA/PsA/AS patients. Between March 2014 and March 2015, 414 patients (214 RA, 125 PsA, and 75 SA) in sinus rhythm without known cardiac disease underwent clinical and color Doppler echocardiographic evaluation and were prospectively followed up. Patients had a mean age of 58 ± 12 years, 64% women. Forty-two patients (10.1%) had a diagnosis of cancer (made before enrollment in 24 cases and in 18 cases during the 36 months of follow-up). Skin cancer was the most frequent malignancy found, followed by thyroid, colon, pancreas, and breast cancer. Patients who had cancer were older with higher systolic blood pressure, more frequent hypertension and moderate/high disease activity, left ventricular (LV) hypertrophy, diastolic dysfunction, and higher ascending aortic stiffness index (AOSI) than those who had not. At multivariate logistic regression analysis, LV diastolic dysfunction and abnormally high AOSI emerged as conditions associated with cancer together with older age and hypertension. Cancer in RA/PsA/AS adults without history of CV disease is closely associated with specific asymptomatic CV abnormalities, such as LV diastolic dysfunction and reduced vascular elasticity, which are independent of age and hypertension.
34691317 The Efficacy of Moxibustion on the Serum Levels of CXCL1 and β-EP in Patients with Rheuma 2021 OBJECTIVE: This study aims to evaluate the efficacy of moxibustion on joint swelling and pain and the levels of C-X-C motif chemokine ligand 1 (CXCL1), β-endorphin (β-EP) in serum of rheumatoid arthritis (RA) patients and to investigate the anti-inflammatory and analgesic mechanism of moxibustion on improving RA. METHODS: Sixty-eight patients with RA were randomly and equally classified into the control and treatment groups. The control group was treated with routine drug therapy, while the treatment group received routine drug therapy and moxibustion. Both groups were treated for eight weeks. The symptoms and laboratory indicators of RA patients were compared in the two groups before and after intervention. RESULTS: Sixty-one patients completed the study: four patients dropped out from the treatment group and three from the control group. Trial endpoints were change (∆) in symptoms, measured by Ritchie's articular index (RAI), swollen joint count (SJC), and laboratory indicators, measured by the level of CXCL1, β-EP, tumor necrosis factor-a (TNF-α), and interleukin-1β (IL-1β). ∆RAI, ∆SJC, ∆CXCL1, ∆β-EP, ∆TNF-α, and ∆IL-1β in the treatment group were superior to the control group (13.50 [14.50] versus 6.00 [13.00] in ∆RAI, 4.00 [3.00] versus 2.00 [4.00] in ∆SJC, 0.04 ± 0.79 ng/mL versus -0.01 ± 0.86 ng/mL in ∆CXCL1, -2.43 [5.52] pg/mg versus -0.04 [4.09] pg/mg in ∆β-EP, 3.45 [5.90] pg/mL versus 1.55 [8.29] pg/mL in ∆TNF-α, and 6.15 ± 8.65 pg/mL versus 1.28 ± 8.51 pg/mL in ∆IL-1β; all P < 0.05). CONCLUSION: Moxibustion can improve the joint swelling and pain symptoms in patients with RA, which may be related to the fact that moxibustion can reduce the release of inflammatory factors in patients with RA and downregulate the level of CXCL1 and increase the level of β-EP at the same time. This trial is registered with ChiCTR-IOR-17012282.
33729387 Predictors of functional capacity as measured by the Glittre activities of daily living te 2021 Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.
33430905 A 9 mRNAs-based diagnostic signature for rheumatoid arthritis by integrating bioinformatic 2021 Jan 11 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune rheumatic disease that carries a substantial burden for both patients and society. Early diagnosis of RA is essential to prevent disease progression and select an optimal therapeutic strategy. However, RA diagnosis is challenging, partly due to a lack of reliable biomarkers. Here, we aimed to explore the diagnostic signature and establish a predictive model of RA. METHODS: The mRNA expression profiling data of GSE17755, containing blood samples of 112 RA patients and 53 healthy control patients, were obtained from the Gene Expression Omnibus (GEO) database, followed by differential expression, GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. A PPI network was constructed to select candidate hub genes, then logistic regression and random forest models were established based on the identified genes. RESULTS: Significantly, we identified 52 differentially expressed genes (DEGs), including 16 upregulated genes and 36 downregulated genes in RA samples compared with control samples. GO and KEGG analysis showed that several immune-related cellular processes were particularly enriched. We identified nine hub genes in the PPI network, including CFL1, COTL1, ACTG1, PFN1, LCP1, LCK, HLA-E, FYN, and HLA-DRA. The logistic regression and random forest models based on the nine identified genes reliably distinguished the RA samples from the healthy samples with substantially high AUC. CONCLUSION: The diagnostic logistic regression and random forest models based on nine hub genes reliably predicted the occurrence of RA. Our findings could provide new insights into RA diagnostics.
33427619 NKG2D ligands in inflammatory joint diseases: analysis in human samples and mouse models. 2021 Sep OBJECTIVES: NKG2D ligands (NKG2DLs) are stress-inducible molecules involved in multiple inflammatory settings. In this work, we quantified MICA, an NKG2DL, in the synovial fluid of patients suffering various arthritides and measured Nkg2dLs gene expression in murine models of acute joint inflammation. METHODS: Soluble MICA (sMICA) was quantified by ELISA is synovial fluids harvested from patients suffering osteoarthritis, rheumatoid arthritis, psoriatic arthritis, calcium pyrophosphate crystal arthritis, urate crystal arthritis and reactive arthritis. Transcripts encoding murine NKG2DLs were quantified by RT-qPCR in the joints of mouse models of rheumatoid arthritis, urate crystal arthritis and osteoarthritis. RESULTS: Marked overproduction of sMICA was observed in the synovial fluid of RA patients. Mouse studies highlighted the complex transcriptional regulation of Nkg2d ligands encoding genes depending on the inflammatory setting and microenvironment CONCLUSIONS: sMICA quantification could be an interesting biomarker to identify acute inflammation in RA patients in whom classical markers (i.e. anti-citrullinated protein antibodies, ACPA) are undetectable.
33640469 Risk of infection associated with Janus Kinase (JAK) inhibitors and biological therapies i 2021 Oct Patients with certain immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), have an increased risk of severe infectious diseases than the general population, which are mainly associated with the immunosuppressive treatments that they receive. These treatments act on the immune system through different mechanisms, causing different degrees of immunosuppression and a variable risk depending on whether the pathogen is a virus, bacteria or fungus. This article reviews the most relevant literature on the subject, which was selected and discussed by a panel of experts. The aim of this article is to review the risk of infections in patients with IBD and RA, and the potential preventive measures.
33180165 Multimodal photoacoustic/ultrasonic imaging system: a promising imaging method for the eva 2021 May OBJECTIVES: We aimed to assess the clinical value of multimodal photoacoustic/ultrasound (PA/US) articular imaging scores, a novel imaging method which can reflect the micro-vessels and oxygenation level of inflamed joints of rheumatoid arthritis (RA). METHODS: Seven small joints were examined by the PA/US imaging system. A 0-3 scoring system was used to semi-quantify the PA and power-Doppler (PD) signals, and the sums of PA and PD scores (PA-sum and PD-sum scores) of the seven joints were calculated. The relative oxygen saturation (SO(2)) values of the inflamed joints were measured and classified into 3 PA+SO(2) patterns. The correlations between the PA/US imaging scores and the disease activity scores were assessed. RESULTS: Thirty-one patients of RA and a total of 217 joints were examined using the PA/US system. The PA-sum had high positive correlations with the standard clinical scores of RA (DAS28 [ESR] ρ = 0.754, DAS28 [CRP] ρ = 0.796, SDAI ρ = 0.836, CDAI ρ = 0.837, p < 0.001), which were superior to the PD-sum (DAS28 [ESR] ρ = 0.651, DAS28 [CRP] ρ = 0.676, SDAI ρ = 0.716, CDAI ρ = 0.709, p < 0.001). For the patients with high PA-sum scores, significant differences between hypoxia and hyperoxia were identified in pain visual analog score (p = 0.020) and patient's global assessment (p = 0.026). The PA+SO(2) patterns presented moderate and high correlation with PGA (ρ = 0.477, p = 0.0077) and VAS pain score (ρ = 0.717, p < 0.001). CONCLUSION: The PA scores have significant correlations with standard clinical scores for RA, and the PA+SO(2) patterns are also related with clinical scores that reflect pain severity. PA may have clinical potential in evaluating RA. KEY POINTS: • Multimodal photoacoustic/ultrasound imaging is a novel method to assess micro-vessels and oxygenation of local lesions. • Significant correlations between multimodal imaging parameters and clinical scores of RA patients were verified. • The multimodal PA/US system can provide objective imaging parameters, including PA scores of micro-vessels and relative SO(2) value, as a supplementary to disease activity evaluation.
33314800 The Pretreatment Gut Microbiome Is Associated With Lack of Response to Methotrexate in Ne 2021 Jun OBJECTIVE: Although oral methotrexate (MTX) remains the anchor drug for rheumatoid arthritis (RA), up to 50% of patients do not achieve a clinically adequate outcome. In addition, there is a lack of prognostic tools for treatment response prior to drug initiation. This study was undertaken to investigate whether interindividual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new-onset RA. METHODS: We performed 16S ribosomal RNA gene and shotgun metagenomic sequencing on the baseline gut microbiomes of drug-naive patients with new-onset RA (n = 26). Results were validated in an additional independent cohort (n = 21). To gain insight into potential microbial mechanisms, we conducted ex vivo experiments coupled with metabolomics analysis to evaluate the association between microbiome-driven MTX depletion and clinical response. RESULTS: Our analysis revealed significant associations of the abundance of gut bacterial taxa and their genes with future clinical response (q < 0.05), including orthologs related to purine and MTX metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome-based model that predicted lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pretreatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes. CONCLUSION: Taken together, these findings are the first step toward predicting lack of response to oral MTX in patients with new-onset RA and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.
33717160 Mini-Review: The Administration of Apoptotic Cells for Treating Rheumatoid Arthritis: Curr 2021 Rheumatoid arthritis (RA) is a chronic immune-mediated disease managed by conventional synthetic drugs, such as methotrexate (MTX), and targeted drugs including biological agents. Cell-based therapeutic approaches are currently developed in RA, mainly mesenchymal stroma cell-based approaches. Early-stage apoptotic cells possess direct and indirect anti-inflammatory properties. During the elimination of dying cells (a process called efferocytosis), specific mechanisms operate to control immune responses. There are compelling evidences in experimental models of arthritis indicating that apoptotic cell administration may benefit joint inflammation, and may even have therapeutic effects on arthritis. Additionally, it has been demonstrated that apoptotic cells could be administered with standard treatments of RA, such as MTX or TNF inhibitors (TNFi), given even a synergistic response with TNFi. Interestingly, apoptotic cell infusion has been successfully experienced to prevent acute graft-vs.-host disease after hematopoietic cell transplantation in patients with hematologic malignancies, with a good safety profile. In this mini-review, the apoptotic cell-based therapy development in arthritis is discussed, as well as its transfer in the short-term to an innovative treatment for patients with RA. The use of apoptotic cell-derived factors, including secretome or phosphatidylserine-containing liposomes, in RA are also discussed.
34538513 Patient perspective on remission in rheumatoid arthritis: Validation of patient reported o 2021 Dec OBJECTIVE: Patients have identified pain, fatigue and independence as the most important domains that need to be improved to define remission in rheumatoid arthritis (RA). This study identified and validated instruments for these domains and evaluated their added value to the ACR/EULAR Boolean remission definition. METHODS: Patients with a 28-joint Disease Activity Score (DAS28) ≤3.2 or in self-perceived remission (declaring their disease activity 'as good as gone') from the Netherlands, Portugal, Australia, and Canada, were assessed at 0, 3 and 6 months for patient-reported outcomes and the WHO-ILAR RA core set. Instrument validity was evaluated cross-sectionally, longitudinally and for the ability to predict future good outcome in terms of physical functioning. Logistic regression quantified the added value to Boolean remission. RESULTS: Of 246 patients, 152 were also assessed at 3, and 142 at 6 months. Most instruments demonstrated construct validity and discriminative capacity. Pain and fatigue were best captured by a simple numerical rating scale (NRS). Measurement of independence proved more complex, but a newly developed independence NRS was preferred. NRS for pain, fatigue and independence, in addition to or instead of patient global assessment did not add enough information to justify modification of the current Boolean definition of remission in RA. CONCLUSION: Key elements of the patient perspective on remission in RA can be captured by NRS pain, fatigue, and independence. Although this study did not find conclusive evidence to improve the current definition of remission in RA, the information from these instruments adds value to the physician's assessment of remission and further bridges the gap between physician and patient.
33084461 Fluorescence optical imaging in patients with active rheumatoid arthritis: a comparison wi 2021 Mar Objectives: This study compared indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) and musculoskeletal ultrasound (MSUS), and explored the significance of the FOI findings based on the association between the FOI and MSUS findings and serum biomarkers in patients with rheumatoid arthritis (RA). The study also explored the association between the FOI findings and patients' joint destruction at the joint-area level.Method: We enrolled 50 consecutive patients with active RA from among the patients hospitalized from May 2014 to March 2016 at Nagasaki University Hospital, Japan. FOI images were acquired with the Xiralite(®) fluorescence imaging system and compared with the patients' clinical examination results and MSUS findings. On the same day, the patients' clinical disease activity and levels of serum biomarkers (including vascular endothelial growth factor) were obtained.Results: Although the FOI detected synovitis with high sensitivity, the frequency of positive findings and the diagnostic performance with MSUS as the reference standard for FOI differed considerably among the phases of FOI as well as among the affected joint regions. The FOI scores were positively correlated with clinical disease activity, MSUS scores, and serum biomarkers. The severity of FOI-proven synovitis was associated with the presence of MSUS-proven bone erosion.Conclusion: FOI is effective for detecting joint inflammation in RA patients, with high accuracy. The severity of the FOI score was closely associated with the joint destruction at the joint-area level. However, the significance of positive FOI findings differed depending on not only the phase of FOI but also the affected joint regions.
34497849 Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Est 2021 BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.
34034706 Therapeutic effect of various ginsenosides on rheumatoid arthritis. 2021 May 25 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. METHODS: The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. RESULTS: All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. CONCLUSION: Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.
34706228 Arthritis flares mediated by tissue-resident memory T cells in the joint. 2021 Oct 26 Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only a subset of joints, distributed in a distinctive pattern for each patient. Pursuing this intriguing pattern, we show that arthritis recurrence is mediated by long-lived synovial resident memory T cells (T(RM)). In three murine models, CD8+ cells bearing T(RM) markers remain in previously inflamed joints during remission. These cells are bona fide T(RM), exhibiting a failure to migrate between joints, preferential uptake of fatty acids, and long-term residency. Disease flares result from T(RM) activation by antigen, leading to CCL5-mediated recruitment of circulating effector cells. Correspondingly, T(RM) depletion ameliorates recurrence in a site-specific manner. Human rheumatoid arthritis joint tissues contain a comparable CD8+-predominant T(RM) population, which is most evident in late-stage leukocyte-poor synovium, exhibiting limited T cell receptor diversity and a pro-inflammatory transcriptomic signature. Together, these findings establish synovial T(RM) as a targetable mediator of disease chronicity in autoimmune arthritis.
33923766 Alcohol Consumption in Rheumatoid Arthritis: A Path through the Immune System. 2021 Apr 16 Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing T(FH) cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol's negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate's effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.
32980481 Anti-rheumatoid arthritis effects of iridoid glucosides from Lamiophlomis rotata (Benth.) 2021 Feb 10 ETHNOPHARMACOLOGICAL RELEVANCE: Lamiophlomisrotata (Benth.) Kudo. has been used to treat trauma bleeding, rheumatism, yellow water disease in traditional Chinese medicine. AIM: The aim of this work was to evaluate the anti-rheumatoid arthritis (RA) activities and underlying mechanisms of the total iridoid glucosides (TIG) from Lamiophlomisrotata (Benth.) Kudo. METHODS: The chemical constituents of TIG was analyzed by high-performance liquid chromatography (HPLC) with seven reference compounds (penstemonoside, chlorotuberside, shanzhiside methyl ester, phloyoside, 7-epliamalbide, phlorigidoside C and lamalbide). The anti-rheumatoid arthritis effects of TIG were investigated by arthritis indexes and paw swelling degrees, as well as histopathological and Micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The impacts of TIG on the level of inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ, IL-17 and IL-10), and the regulation of OPG/RANKL/NF-κB pathways were determined by the ELISA and western blot, respectively. RESULTS: TIG significantly reduced the arthritis indexes and paws swelling in AIA rats, attenuated the inflammation and bone destruction in joint tissues, reduced the generation of pro-inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ and IL-17, as well as increased the generation of anti-inflammatory cytokine IL-10 in serum. Moreover, TIG markedly inhibited the expression of p-IKK-α, p-IκB and p-p65, and decreased the ratio of OPG/RANKL in the synovial tissues. CONCLUSION: TIG possessed significant anti-RA activities on adjuvant-induced arthritis, which might be ascribed to the regulation of inflammatory cytokines IL-1β, TNF-α, IL-6, IFN-γ IL-17 and IL-10, as well as inhibition of OPG/RANKL/NF-κB signaling pathways.
34319448 Decrease in handgrip strength in rheumatoid arthritis (RA): is there a sex-related differe 2021 Oct Rheumatoid arthritis occurs two to three times more often in women than in men and it has been less studied in men. The results of gender influence on clinical course of the disease are contradictory. The aim of this study is to determine the difference in handgrip strength between female and male RA patients in comparison to healthy individuals. The study included 100 RA patients and 100 healthy individuals (50% were male in both groups). Handgrip strength was measured in both hands using a dynamometer. A two-way ANCOVA was used to analyse the data and age was included in the study as covariate. The results show that both male and female RA patients have lower handgrip strength compared to healthy individuals. The analysis of gender and disease interaction has shown that male RA patients have lower handgrip strength than female RA patients in comparison with the healthy group, age adjusted. This interaction is evident and statistically significant in both right hand (F 1, 195) = 14.62; p < 0.01) and left hand (F 1, 195) = 20.54; p < 0.01). The common-language effect size has shown that there is 92% (right hand) and 93% (left hand) chance that male individual will have stronger handgrip than his female counterpart. In RA patients, there is 77% chance for both hands that male will have stronger handgrip. Men and women with RA have significantly lower handgrip strength compared to healthy individuals and the difference is more pronounced in men which was not previously observed in the literature.
34224949 The pathogenic, therapeutic and diagnostic role of exosomal microRNA in the autoimmune dis 2021 Sep 15 Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases.