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ID PMID Title PublicationDate abstract
35302258 Immunomodulatory effects of curcumin in systemic autoimmune diseases. 2022 Apr Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto-antigen outbreak, inflammation, and multi-organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.
35320820 Detection of salivary citrullinated cytokeratin 13 in healthy individuals and patients wit 2022 The immune response to citrullinated peptides in the mucosa has been suggested to play an important role in the transition from pre-onset rheumatoid arthritis (RA) to clinically evident RA. Although there are reports indicating the presence of anti-citrullinated peptide antibodies in the saliva, few studies have reported citrullinated peptide detection in human saliva. This study aimed to identify citrullinated peptides in human saliva and discuss their clinical significance. Saliva samples were collected from 11 patients with RA and from 20 healthy individuals. Citrullinated peptides were detected using an anti-modified citrulline (AMC) antibody. Saliva from the healthy individuals was subjected to two-dimensional protein electrophoresis to isolate citrullinated peptides, which were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and mass spectrometry by peptide mass fingerprinting. The results were corroborated by immunoprecipitation (IP)-western blotting. The signal intensities of the bands precipitated with anti-cytokeratin 13 (CK13) and AMC antibodies were quantified. The signal intensity ratio of the band produced by the AMC antibody was divided by that of the band produced by the anti-CK13 antibody to calculate the citrullinated CK13 (Cit-CK13) ratio. A citrullinated peptide band corresponding to a molecular weight of approximately 50 kDa was detected in the saliva of healthy individuals, and identified as CK13 via mass spectrometry and IP-western blotting. No significant difference was observed between the salivary Cit-CK13 ratios of patients with RA and healthy participants (p = 0.605). This is the first study to show that Cit-CK13 is present in human saliva, and that there is no significant difference between the Cit-CK13 ratios of patients with RA and healthy individuals, suggesting that salivary Cit-CK13 content and RA development may not be associated. The physiological and pathological roles of Cit-CK13 in the oral cavity, and its responsiveness to mucosal immunity, remain unknown and will be the subject of further investigation.
35263670 An updated review of the effects of eicosapentaenoic acid- and docosahexaenoic acid-derive 2022 Jun Resolvins are biosynthesized from omega-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in vivo by means of enzymatic activities, and these factors can attenuate inflammation and promote tissue regeneration. Inflammatory bone disorders can lead to bone loss and thereby be harmful to human health. The link between bone preservation and resolvins has been discussed in some experimental studies. Significant evidence has shown that resolvins benefit bone health and bone preservation by promoting the resolution of inflammation and directly regulating osteoclasts and osteoblasts. Therefore, this review highlights the role and beneficial impact of resolvins derived from EPA and DHA on inflammatory bone disorders, such as rheumatoid arthritis and periodontitis. In addition, the mechanisms by which resolvins exert their beneficial effects on bone preservation have also been summarized based on the available literature.
35633584 Progression from palindromic rheumatism to rheumatoid arthritis after COVID-19 vaccination 2022 Jan Infections including COVID-19 infection are associated with immune overactivation and hyperinflammation, and cases of incident inflammatory arthritis after COVID-19 and other respiratory viral infections have been reported. Theoretical concerns of autoimmunity due to molecular mimicry exist with vaccines including vaccines for COVID-19, and rare cases of flares of underlying chronic inflammatory disorders such as systemic lupus erythematosus have been reported after COVID-19 vaccination. Here we present the case of a patient with a 7-year history of well-controlled palindromic rheumatism who developed rheumatoid arthritis 2 weeks after vaccination for COVID-19. This is the first such case to our knowledge, and further studies can elaborate on the risk of autoimmunity due to COVID-19 vaccines if one exists. Given the overall safety and efficacy of COVID-19 vaccines, the proven benefits of vaccinating vulnerable patients with autoimmune disorders outweigh this potential theoretical risk of autoimmune disease flare, and vaccinations in this at-risk population shall be strongly encouraged.
35042119 miR-223 in exosomes from bone marrow mesenchymal stem cells ameliorates rheumatoid arthrit 2022 Mar BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease with major clinical manifestations of human limb joint invasion, joint synovitis, and symmetrical lesions. In recent years, bone marrow mesenchymal stem cells (BMSCs) have been found to have low immunogenicity and immunomodulatory effects, which can regulate other types of cells through exosomes. However, the effect of BMSCs on immune response in the progression of RA has not been fully elucidated. AIMS: The current research aimed to investigate the therapeutic effect of microRNA (miR)-223 in exosomes secreted by BMSCs on immune response in the progression of RA. METHODS: Firstly, BMSCs were isolated and extracted, and then the influence of BMSCs on the level of inflammatory cytokines was detected by enzyme linked immunosorbent assay (ELISA). Exosomes from BMSCs were extracted and characterized. Some key autoimmune response genes and their protein products were detected in vivo and in vitro by real-time quantitative PCR, western blot and ELISA. Finally, the targeting relationship between miR-223 and NLR family pyrin domain-containing 3 (NLRP3) was predicted by bioanalytical software and verified by luciferase reporter assay and rescue experiments in vitro. RESULTS: Exosomes from BMSCs could inhibit the release of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-18 (IL-18), and NLRP3 activation in macrophages and RA rats. In addition, we predicted online that miR-223 could target NLRP3 and provided a possible regulation pathway for the anti-inflammatory effects of BMSCs-secreted exosomes. Furthermore, we further confirmed that miR-223 could target and inhibit the expression of NLRP3. CONCLUSION: Taken together, these findings suggest that miR-223 carried by BMSCs-derived exosomes targets NLRP3 to regulate the activation of inflammasomes, which therefore can be served as a possible therapy for RA.
35571560 Breast Implant-Associated Immunological Disorders. 2022 BACKGROUND: Breast implants are commonly placed postbreast cancer reconstruction, cosmetic augmentation, and gender-affirming surgery. Breast implant illness (BII) is a systemic complication associated with breast implants. Patients with BII may experience autoimmune symptoms including fatigue, difficulty concentrating, hair loss, weight change, and depression. BII is poorly understood, and the etiology is unknown. The purpose of this literature review is to characterize BII autoimmune disorders and determine possible causes for its etiology. METHODS: The PubMed, Google Scholar, Embase, Web of Science, and OVID databases were interrogated from 2010 to 2020 using a query strategy including search term combinations of "implants," "breast implant illness," "autoimmune," and "systemic illness." RESULTS: BII includes a spectrum of autoimmune symptoms such as fatigue, myalgias/arthralgias, dry eyes/mouth, and rash. A review of epidemiological studies in the past ten years exhibited evidence affirming an association between breast implants and autoimmune diseases. The most commonly recognized were Sjogren's syndrome, rheumatoid arthritis, systemic sclerosis, chronic fatigue syndrome, and Raynaud's syndrome. Explantation resulted in alleviation of symptoms in over 50% of patients, strengthening the hypothesis linking breast implants to BII. Studies have shown that silicone is a biologically inert material and unlikely to be the cause of these symptoms. This is supported by the fact that increased risk of autoimmune disease was also reported in patients with other implantable biomaterials such as orthopedic implants. Recent studies shed light on a possible role of bacterial biofilm and subsequent host-pathogen interactions as a confounding factor to this problem. CONCLUSION: BII could be dependent on biofilm infection and the microenvironment around the implants. The true pathophysiology behind these complaints must be further investigated so that alternative treatment regimens other than explantation can be developed. Translational significance of these studies is not limited to breast implants but extends to other implants as well.
35219333 Plasma interleukin-23 and circulating IL-17A(+)IFNγ(+) ex-Th17 cells predict opposing out 2022 Feb 26 OBJECTIVES: TNF-α inhibitors are widely used in rheumatoid arthritis (RA) with varying success. Response to TNF-α inhibition may reflect the evolution of rheumatoid inflammation through fluctuating stages of TNF-α dependence. Our aim was to assess plasma concentrations of Th-17-related cytokines and the presence of circulating effector T-cells to identify predictors of response to TNF-α inhibitors. METHODS: Ninety-three people with RA were seen prior to and 4-6 months after commencing etanercept or adalimumab. Plasma concentrations of Th17-related cytokines, circulating effector T-cells, their production of relevant transcription factors and intracellular cytokines were measured at baseline. EULAR response criteria were used to define poor (ΔDAS28 ≤ 1.2 and/or DAS28 > 3.2) and good (ΔDAS28 > 1.2 and DAS28 ≤ 3.2) responders. Multivariate logistic regression was used to identify predictors of response. RESULTS: Participants with plasma IL-23 present at baseline were more likely to be poor responders [15/20 (75%) of IL-23(+) versus 36/73 (49.3%) of IL-23(-); p = 0.041]. While frequencies of Th1, Th17, ex-Th17 and T(reg) cell populations were similar between good and poor responders to anti-TNF therapy, IL-17A(+)IFNγ(+) ex-Th17 cells were more prevalent in good responders (0.83% of ex-T(H)17 cells) compared to poor responders (0.24% of ex-Th17 cells), p = 0.023. Both plasma IL-23 cytokine status (OR = 0.17 (95% CI 0.04-0.73)) and IL-17A(+)IFNγ(+) ex-Th17 cell frequency (OR = 1.64 (95% CI 1.06 to 2.54)) were independently associated with a good response to anti-TNF therapy. Receiver operator characteristic (ROC) analysis, including both parameters, demonstrated an area under the ROC curve (AUC) of 0.70 (95% CI 0.60-0.82; p = 0.001). CONCLUSIONS: Plasma IL-23 and circulating IL-17A(+)IFNγ(+) ex-Th17 cells are independently associated with response to anti-TNF therapy. In combination, plasma IL-23 and circulating IL-17A(+)IFNγ(+) ex-Th17 cells provide additive value to the prediction of response to anti-TNF therapy in RA.
35358930 Geniposide alleviates VEGF-induced angiogenesis by inhibiting VEGFR2/PKC/ERK1/2-mediated S 2022 Jun BACKGROUND: Rheumatoid arthritis (RA) is an angiogenesis-dependent disease caused by the imbalance of pro- and anti-angiogenic factors. More effective strategies to block synovial angiogenesis in RA should be studied. Geniposide (GE), a natural product isolated from the fruit of Gardenia jasminoides Ellis (GJ), is reported to have anti-inflammatory, anti-angiogenic and other pharmacological effects. However, the underlying mechanism through which GE affects synovial angiogenesis in RA remains unclear. PURPOSE: In this research, we aimed to elucidate the effect and potential mechanisms of GE on angiogenesis in RA. MATERIALS AND METHODS: Synovial angiogenesis in patients with RA and a rat model of adjuvant arthritis (AA) was detected by hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), and western blottiing. The biological functions of vascular endothelial cells (VECs) and sphingosine kinase 1 (SphK1) translocation were checked by CCK-8, EdU, Transwell, tube formation, co-immunoprecipitation assays, and laser scanning confocal microscopy. The effect of the SphK1 gene on angiogenesis was assessed by transfection of SphK1-siRNA in cells and mices. The effect of GE on VEGF-induced angiogenesis was measured by Matrigel plug assay in a mouse model of AA. RESULTS: GE effectively inhibited synovial angiogenesis and alleviated the disease process. SphK1, as a new regulatory molecule, has a potentially important relationship in regulating VEGF/VEGFR2 and S1P/S1PR1 signals. SphK1 translocation was activated via the VEGFR2/PKC/ERK1/2 pathway and was closely linked to the biological function of VECs. GE significantly reduced SphK1 translocation, thereby ameliorating the abnormal biological function of VECs. Furthermore, after transfection of SphK1 siRNA in VECs and C57BL/6 mice, silencing SphK1 caused effectively attenuation of VEGF-induced VEC biological functions and angiogenesis. In vivo, the Matrigel plug experiment indicated that GE significantly inhibited pericyte coverage, basement membrane formation, vascular permeability, and fibrinogen deposition. CONCLUSIONS: Our findings suggest that GE inhibited VEGF-induced VEC biological functions and angiogenesis by reducing SphK1 translocation. Generally, studies have revealed that GE down-regulated VEGFR2/PKC/ERK1/2-mediated SphK1 translocation and inhibited S1P/S1PR1 signaling activation, thereby alleviating VEGF-stimulated angiogenesis. The above evidences indicated that angiogenesis inhibition may provide a new direction for RA treatment.
35103239 Clinical-Like Cryotherapy in Acute Knee Arthritis Protects Neuromuscular Junctions of Quad 2022 Rheumatoid arthritis is an autoimmune and inflammatory disease that affects synovial joint tissues and skeletal muscle. Clinical-like cryotherapy benefits signs of joint inflammation in knee osteoarthritis after 60 days of anterior cruciate ligament transection surgery. However, it is unknown whether it also benefits acute knee arthritis (e.g., reduces inflammatory process and protects neuromuscular junction [NMJ] and muscle fibers). We aimed to analyze the effects of clinical-like cryotherapy on NMJ and quadriceps muscle fibers in a model of acute knee arthritis. Twenty-four male C57BL/6 mice (20 to 25 g) were randomly allocated into three groups: control (mice with no intervention), antigen-induced arthritis (AIA; mice sensitized and immunized with intra-articular [i.a.] injection of methylated bovine serum albumin [mBSA]), and AIA+cryotherapy (mice sensitized, immunized with i.a. injection of mBSA, and submitted to a clinical-like cryotherapy protocol). Twenty-one days after sensitization, arthritis was induced in immunized mice via i.a. injection of mBSA (100 μg/joint). Two clinical-like cryotherapy sessions (crushed ice pack for 20 min) were applied two hours apart. The first session was applied immediately after i.a. injection of mBSA. The quadriceps was removed two hours after the second clinical-like cryotherapy session for morphological analysis of muscle fibers (cross-sectional area), frequency distribution of muscle fiber area (%), and NMJ (area, perimeter, and maximum diameter). Gene expressions of mRNA involved in NMJ signaling (γ-nAChR, α1-nAChR, ε-nAChR, Agrin-MusK-Rapsyn, α-dystrobrevin, and utrophin) and atrophy (muscle RING-finger protein-1 and Atrogin-1) pathways were analyzed. Inflammatory signs were assessed in knee joint (swelling, articular surface temperature, and neutrophil migration in synovial fluid). Regarding morphological analysis of muscle fibers, 180 to 270 and >270 μm(2) classes were higher in the AIA+cryotherapy than the AIA group. Area, perimeter, and maximum diameter of NMJ also increased in the AIA+cryotherapy compared with the control group. Agrin mRNA expression increased in the AIA+cryotherapy compared with the control and AIA groups. In the atrophy pathway, Atrogin-1 increased compared with the control and AIA groups. The AIA+cryotherapy group reduced knee swelling and neutrophil migration compared with the AIA group. In conclusion, clinical-like cryotherapy increased Agrin expression, contributing to NMJ maintenance and increased Atrogin-1 expression, thus protecting NMJ and muscle fiber. Furthermore, clinical-like cryotherapy reduced inflammatory signs (swelling and neutrophil migration) of acute knee arthritis.
35107535 The burden of low back pain, rheumatoid arthritis, osteoarthritis, and gout and their resp 2022 INTRODUCTION: Musculoskeletal (MSK) disorders are a major cause of disability worldwide. Different modifiable risk factors are associated to these disorders. The objective of this study was to analyze the burden of low back pain (LBP), rheumatoid arthritis (RA), osteoarthritis (OA), and gout, attributable to risk factors, in 2017. METHODS: The burden of LBP, RA, OA, and gout, and attributable risk factors were analyzed using data extracted from the Global Burden of Disease (GBD) Brasil-2017 study. Descriptive analysis was conducted to compare disability-adjusted life years (DALY) rates between sexes and age groups (15-49 and 50-69 years), in 2017. RESULTS: The highest rates of DALY due to LBP were attributed to occupational ergonomic factors in the 15-49-year group, regardless of sex and males aged 50-69 years, whereas smoking was the major contributor in the 50-69-year female group. RA-related DALY rates were attributed to smoking and were higher among women aged 50-69 years. High body mass index (BMI) was the most relevant risk factor for the burden of OA, with higher rates detected in the 50-69-year group, and it was the most significant risk factor for DALY rate attributed to gout, regardless of sex or age group. CONCLUSIONS: Occupational surveillance measures are indicated to prevent LBP. Actions to decrease smoking and overweight, and the surveillance of weight gain are warranted to decrease the burden of LBP, RA and OA, and gout, respectively. These actions will be more effective if age and sex differentials are considered in planning.
35185862 Systematic Review of Safety and Efficacy of Second- and Third-Generation CD20-Targeting Bi 2021 BACKGROUND: B cells can contribute to immune-mediated disorders. Targeting CD20 has proved to be efficacious in several B cell-mediated immunopathologies, as illustrated by the use of rituximab, the first anti-CD20 monoclonal antibody (mAb). Following rituximab, second- and third-generation anti-CD20 mAbs have been developed and tried in immune-mediated diseases, including obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab. However, their safety and efficacy has not been systematically reviewed. OBJECTIVE: To evaluate safety and efficacy of obinutuzumab, ocrelizumab, ofatumumab, ublituximab, and veltuzumab for the treatment of immune-mediated disorders compared to placebo, conventional treatment or other biologics. METHODS: The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 22 July 2021 concentrating on immune-mediated disorders. RESULTS: The literature search identified 2220 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 27 articles were finally included in a narrative synthesis. CONCLUSIONS: Obinutuzumab has shown promising results in a case series of patients with phospholipase A(2) receptor-associated membranous nephropathy and mixed results in systemic lupus erythematosus. Ocrelizumab has been approved for the use in patients with relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab was also tested in patients with rheumatoid arthritis, demonstrating promising results, and in systemic lupus erythematosus, revealing mixed results; however, in these conditions, its use was associated with increased risk of serious infections. Ofatumumab received approval for treating patients with relapsing-remitting multiple sclerosis. Moreover, ofatumumab showed promising results in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis, rheumatoid arthritis, and systemic lupus erythematosus, as well as mixed results in phospholipase A(2) receptor-associated membranous nephropathy. Ublituximab was assessed in relapsing-remitting multiple sclerosis and neuromyelitis optica spectrum disorder, with promising results, however, the included number of patients was too small to conclude. Veltuzumab was tested in patients with immune thrombocytopenia resulting in improved platelet counts. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD4201913421.
35488290 The angiopoietin-like protein 4, apolipoprotein C3, and lipoprotein lipase axis is disrupt 2022 Apr 29 BACKGROUND: Modulators of triglyceride metabolism include lipoprotein lipase (LPL), angiopoietin-like protein 4 (ANGPTL4), and apolipoprotein C-3 (ApoC3). There is evidence on the influence of this triangle of molecules on an increased risk of atherosclerotic cardiovascular disease (CV) in the general population. Patients with rheumatoid arthritis (RA) present changes in lipid profiles and accelerated CV disease. In the present study, we set out to study whether the ANGPTL4, ApoC3, and LPL axis differs in subjects with RA compared to controls. In a further step, we investigated the relationship of this axis with subclinical atherosclerosis in patients with RA. METHODS: Cross-sectional study that included 569 individuals, 323 patients with RA and 246 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in patients and controls. Carotid intima-media thickness (cIMT) and carotid plaques were assessed in RA patients. A multivariable analysis was performed to assess whether the ANGPTL4, ApoC3, and LPL axis was altered in RA and to study its relationship with RA dyslipidemia and subclinical carotid atherosclerosis. RESULTS: Most lipid profile molecules did not differ between patients and controls. Despite this, and after fully multivariable analysis including CV risk factors, use of statins, and changes in the lipid profile caused by the disease itself, patients with RA showed higher serum levels of ANGPTL4 (beta coef. 295 [95% CI 213-376] ng/ml, p<0.001) and ApoC3 (beta coef. 2.9 [95% CI 1.7-4.0] mg/dl, p<0.001), but lower circulating LPL (beta coef. -174 [95% CI -213 to -135] ng/ml, p<0.001). ANGPTL4 serum levels were positively and independently associated with a higher cIMT in patients with RA after fully multivariable adjustment. CONCLUSION: The axis consisting in ANGPTL4, ApoC3, and LPL is disrupted in patients with RA. ANGPTL4 serum levels are positively and independently associated with a higher cIMT in RA patients.
33974929 Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic 2022 Jan BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition involving loss of B-cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined. OBJECTIVE: Our aim was to identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD. METHODS: We sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative mAbs were expressed and their specificities characterized by using cytokine microarrays. The role of anti-IL-1 receptor antagonist (IL-1RA) autoantibodies was investigated by using in vitro assays. RESULTS: We identified strong reactivity against human IL-1RA by using a clonally expanded plasmablast-derived mAb from a patient with IgG4-RD. Plasma from patients with IgG4-RD exhibited elevated levels of reactivity against IL-1RA compared with plasma from the controls and neutralized IL-1RA activity, resulting in inflammatory and fibrotic mediator production in vitro. IL-1RA was detected in lesional tissues from patients with IgG4-RD. Patients with anti-IL-1RA autoantibodies of the IgG4 subclass had greater numbers of organs affected than did those without anti-IL-1RA autoantibodies. Peptide analyses identified IL-1RA epitopes targeted by anti-IL-1RA antibodies at sites near the IL-1RA/IL-1R interface. Serum from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also had elevated levels of anti-IL-1RA autoantibodies compared with those of the controls. CONCLUSION: A subset of patients with IgG4-RD have anti-IL-1RA autoantibodies, which promote proinflammatory and profibrotic meditator production via IL-1RA neutralization. These findings support a novel immunologic mechanism underlying the pathogenesis of IgG4-RD. Anti-IL-1RA autoantibodies are also present in a subset of patients with SLE and RA, suggesting a potential common pathway in multiple autoimmune diseases.
35456453 Construction of a ceRNA Network Related to Rheumatoid Arthritis. 2022 Apr 6 (1) Background: Rheumatoid arthritis (RA) is a common systemic autoimmune disease affecting many people and has an unclear and complicated physiological mechanism. The competing endogenous RNA (ceRNA) network plays an essential role in the development and occurrence of various human physiological processes. This study aimed to construct a ceRNA network related to RA. (2) Methods: We explored the GEO database for peripheral blood mononuclear cell (PBMC) samples and then analyzed the RNA of 52 samples (without treatment) to obtain lncRNAs (DELs), miRNAs (DEMs), and mRNAs (DEGs), which can be differentially expressed with statistical significance in the progression of RA. Next, a ceRNA network was constructed, based on the DELs, DEMs, and DEGs. At the same time, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were used to validate the possible function of the ceRNA network. (3) Results: Through our analysis, 389 DELs, 247 DEMs, and 1081 DEGs were screened. After this, a ceRNA network was constructed for further statistical comparisons, including 16 lncRNAs, 1 miRNA, and 15 mRNAs. According to the GO and KEGG analysis, the ceRNA network was mainly enriched in the mTOR pathway, the dopaminergic system, and the Wnt signaling pathway. (4) Conclusions: The novel ceRNA network related to RA that we constructed offers novel insights into and targets for the underlying molecular mechanisms of the mTOR pathway, the dopaminergic system, and the Wnt signaling pathway (both classic and nonclassic pathways) that affect the level of the genetic regulator, which might offer novel ways to treat RA.
35436058 Clinical implications of autoantibodies to extractable nuclear antigens in rheumatoid arth 2022 Apr The purpose of this study was to assess the prevalence of autoantibodies against extractable nuclear antigens (ENAs), anti-Ro/SSA, anti La/SSB, anti Jo-1, ribo-nucleoproteins (anti UI-RNP) and antibodies to Smith (anti-Sm) in rheumatoid arthritis (RA) patients and to detect the relationship between the existence of these autoantibodies and clinical presentation, radiological damage, and disease activity markers. The study, included 57 RA patients and 35 normal controls, was conducted in Al-Quwayiya General Hospital. Sera were obtained from patients and controls to carry out Hs-CRP, ESR, RF factors, ANA and ACPA IgG. Anti-Sm, anti-U1-RNP, anti-Ro/SSA, anti-La/SSB, and anti-Jo-1 were measured using the Alegria® assay. ESR was 23.8±6.5, while CRP was 16.19±7.15 in RA patients. RF was detected in 23 (40.35%) patients and ACPA in 54 (94.73%), while ANA was positive in 14 (24.56%) cases. Anti-Ro/SSA was detected in 8 (14.03%) patients, anti-La/SSB in 3 (5.26%), anti-Jo-1 was found in 2 cases (3.50%), and anti-RNP in 1 (1.75%). Anti-Ro/SSA had a significant negative relationship with sex (r=-0.220, P=0.001), but a positive correlation was observed with sicca symptoms (r=0.149, P=0.02). Anti-La/SSB antibodies correlated positively with swollen joint count (r=0. 0.225, P=0.001), tender joint count (r=0.219, P=0.001) and ANA (r=0.367, P < 0.001). Anti-Jo-1 antibodies showed a significant positive correlation with interstitial lung disease (r=-0.429, P≤0.001). Anti-Ro/SSA had a significant positive correlation with RF titer (r=0.259, P < 0.001) and ANA (r=0.498, P < 0.001). Anti-La/SSB had significant positive correlation with ANA (r=0.372, P < 0.001). Anti-Jo-1 showed a significant positive correlation with RF titer (r=0.141, P < 0.040) and ANA (r=0.249, P < 0.001). Anti-RNP showed a significant positive correlation with ACPA titre (r=0.288, P < 0.001) and ANA (r=0.159, P < 0.018). We conclude that ENA autoantibodies are crucial and need to be correlated with clinical diagnosis and other serological testing for early diagnosis and intervention of the RA.
35212850 Nerolidol: a potential approach in rheumatoid arthritis through reduction of TNF-α, IL-1Π2022 Apr Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1 mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800 mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1β were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1β, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.
35137914 Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therap 2022 Apr Tumor necrosis factor‑α (TNF‑α) is a pleiotropic pro‑inflammatory cytokine that contributes to the pathophysiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF‑α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), both the two variants, soluble and transmembrane TNF‑α, can exert multiple biological effects according to different settings. They can either function as immune regulators, impacting B‑, T‑ and dendritic cell activity, modulating the autoimmune response, or as pro‑inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF‑α, focusing on the different effects that TNF‑α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti‑TNF‑α therapies in preclinical and clinical trials SLE are discussed.
34800087 The composition of the lung microbiome differs between patients with dermatomyositis and r 2022 Jan Dermatomyositis and rheumatoid arthritis are inflammatory diseases that affect the skeletal muscles and joints, respectively. A common systemic complication of these diseases is interstitial lung disease (ILD), which leads to a poor prognosis and increased mortality. However, the mechanism for the initiation and development of ILD in patients with dermatomyositis is currently unknown. In the present study, we used 16S rRNA high-throughput sequencing to profile the bacterial community composition of bronchoalveolar lavage fluid of patients with dermatomyositis associated with ILD (DM-ILD; shortened to DM below), rheumatoid arthritis associated with ILD (RA-ILD; shortened to RA below) and healthy controls (N) aiming to understand the differences in their lung microbiota and to predict gene function. We found that there were more operational taxonomic units (OTUs) in the lung microbiota of both RA and DM compared to N, although there was no significant difference in the number of OTUs between RA and DM. Similarly, the diversity in alphaproteobacteria differed between RA and DM compared to N, but not between RA and DM. The lung microbiota of RA, DM and N was mainly comprised of five phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria, with 10 dominant genera. Despite the similarity in microbiota composition, we also identified 41 OTUs of lung microbiota that differed among RA, DM and N. Additionally, linear discriminant analysis effect size and linear discriminant analysis genus scores confirmed that 31 microbial biomarkers were clearly distinguished among RA, DM and N. The functional and metabolic alterations of the lung microbiota among RA, DM and N were predicted using picrust, and differentially abundant KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were identified. Research on the lung microbiota of patients with DM and RA may open new opportunities for developing biomarkers to identify high-risk patients.
35269591 The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune 2022 Feb 23 The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.
34988877 Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Dise 2022 Jun The coronavirus disease 2019 (COVID-19) pandemic has prompted significant changes in patient care in rheumatology and gastroenterology, with clinical guidance issued to manage ongoing therapy while minimising the risk of nosocomial infection for patients and healthcare professionals (HCPs). Subcutaneous (SC) formulations of biologics enable patients to self-administer treatments at home; however, switching between agents may be undesirable. CT-P13 SC is the first SC formulation of infliximab that received regulatory approval and may be termed a biobetter as it offers significant clinical advantages over intravenous (IV) infliximab, including improved pharmacokinetics and a convenient mode of delivery. Potential benefits in terms of reduced immunogenicity have also been suggested. With a new SC formulation, infliximab provides an additional option for dual formulation, which enables patients to transition from IV to SC administration route without changing agent. Before COVID-19, clinical trials supported the efficacy and safety of switching from IV to SC infliximab for patients with rheumatoid arthritis and inflammatory bowel disease (IBD), and SC infliximab may have been selected on the basis of patient and HCP preferences for SC agents. During the pandemic, patients with rheumatic diseases and IBD have successfully switched from IV to SC infliximab, with some clinical benefits and high levels of patient satisfaction. As patients switched to SC therapeutics, the reduction in resource requirements for IV infusion services may have been particularly welcome given the pandemic, facilitating reorganisation and redeployment in overstretched healthcare systems, alongside pharmacoeconomic benefits and a reduction in exposure to nosocomial infection. Telemedicine and contactless healthcare have been pushed to the forefront during the pandemic, and a lasting shift towards remote patient management and community/home-based drug administration is anticipated. SC infliximab supports the implementation of this paradigm for future improvements of healthcare value delivered. The accumulation of real-world data during the pandemic supports the high level of confidence, with patients, physicians, and healthcare systems benefitting from its uptake.