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ID PMID Title PublicationDate abstract
35153034 Development and feasibility of 4 checklists for the evaluation of comorbidity in patients 2022 Feb OBJECTIVE: To develop and assess the feasibility in daily practice of four comorbidity checklists, for common use in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: A multidisciplinary panel of experts on comorbidity was established. Data from the GECOAR, GECOAX and GECOAP projects were analysed and a narrative literature review in Medline on RA, axSpA and PsA comorbidity was performed in order to select the most relevant and common comorbidities across the three diseases. With these results and those obtained from a focus group of patients, in a nominal group meeting, the experts generated preliminary checklists. These were afterwards modified by an external evaluation by two associations, a patients' association and an association of health professionals related to rheumatology. As a result, the final checklists were generated. A cross-sectional study was conducted to test the feasibility of three of the checklists in daily practice, in which eight health professionals evaluated the checklists in five patients with RA, five with axSpA and five with SpA. RESULTS: Four comorbidity checklists were designed, three for health professionals (one to assess current comorbidity, one on prevention/health promotion and one with the referral criteria to other health professionals), and another for patients. The feasibility study showed them to be simple, clear, and useful for use in routine clinical practice. CONCLUSIONS: The use of specific and common checklists for patients with RA, axSpA and PsA is feasible and might contribute favorably to their prognosis as well as in daily practice.
35193490 Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats. 2022 Feb 22 Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1(β), interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.
35114374 Development of a hyperbranched polymer-based methotrexate nanomedicine for rheumatoid arth 2022 Apr 1 Methotrexate (MTX) is an effective disease modifying anti-rheumatic drug, but can cause significant hepatotoxicity and liver failure in some individuals. The goal of this work was to develop a MTX-conjugated hyperbranched polymeric nanoparticle based on oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and examine its ability to selectively deliver MTX to rheumatic joints while sparing the liver. MTX was conjugated to the hyperbranched polymer via a matrix metalloproteinase-13 cleavable peptide linker. Two populations of nanoparticles were produced, with sizes averaging 20 and 200nm. Tri-peptide (FFK)-modified MTX was liberated in the presence of matrix metalloproteinase 13 (MMP-13)and showed 100 to 1000-fold lower antiproliferative capacity in monocytic THP-1 cells compared to unmodified MTX, depending on whether the gamma-carboxylate of MTX was functionalized with O-tert-butyl. Nanoparticles showed prolonged plasma exposure after intravenous injection with a terminal half-life of approximately 1 day, but incomplete (50%) absorption after subcutaneous administration. Nanoparticles selectively accumulated in inflamed joints in a rat model of rheumatoid arthritis and showed less than 5% biodistribution in the liver after 5 days. MTX-OtBu nanoparticles also showed no hepatocellular toxicity at 500 μM MTX equivalents. This work provides support for the further development of OEGMA-based hyperbranched polymers as MTX drug delivery systems for rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Nanomedicines containing covalently conjugated methotrexate offer the potential for selective accumulation of the potent hepatotoxic drug in rheumatic joints and limited liver exposure. One limitation of the high surface presentation of methotrexate on a nanoparticle surface, however, is the potential for enhanced liver uptake. We developed several OEGMA-based hyperbranched polymers containing alpha-carboxyl modified and unmodified methotrexate conjugated via an MMP-13 cleavable hexapeptide linker. The modified methotrexate polymer showed promising in vitro and in vivo behavior warranting further development and optimization as an anti-rheumatic nanomedicine. This work presents a new avenue for further research into the development of hyperbranched polymers for rheumatoid arthritis and suggests interesting approaches that may overcome some limitations associated with the translation of anti-rheumatic nanomedicines into patients.
35164656 LncRNA OSER1-AS1 regulates the inflammation and apoptosis of rheumatoid arthritis fibrobla 2022 Mar It has been reported that long noncoding RNAs (LncRNAs) take part in the progression and occurrence of rheumatoid arthritis (RA). The current work aimed to dig the effect of lncRNA OSER1-AS1 on RA and the associated mechanism. Quantitative real-time polymerase chain reaction (qRT-PCR) was made to decide that OSER1-AS1 was significantly lowly expressed in synovial tissue and serum of RA patients, which was consistent in RA-FLSs cell lines. The result of ROC curve indicated that OSER1-AS1 could be a diagnostic biomarker for RA patients. Cell Counting Kit-8 assay (CCK-8), EdU staining and flow cytometry were performed to explore the effect of OSER1-AS1 on RA-FLSs in vitro. Relative levels of interleukin-1 (IL-1), interleukin-6 (IL-6), matrix metalloproteinases-3 (MMP-3) were detected by ELISA and the result displayed that overexpression of OSER1-AS1 inhibited RA-induced inflammatory production of IL-1, IL-6 and MMP3. Bioinformatics analysis, luciferase reporter, RNA immunoprecipitation assays (RIP) and RNA pull-down assay were conducted to confirm the binding between microRNA-1298-5p (miR-1298-5p) and OSER1-AS1 or E2F transcription factor 1 (E2F1). Mechanistically, OSER1-AS1 serves as a competing endogenous (ceRNA) in RA-FLSs through the sponge of miR-1298-5p and increase in the expression of E2F1. Further restoration experiments revealed that miR-1298-5p mimics and E2F1 silencing could partially reverse the inhibiting effect of OSER1-AS1 overexpression on propagation and apoptosis in RA-FLSs. The results illustrated the biological mechanism of OSER1-AS1/miR-1298-59/E2F1 axis in RA progression. The outcomes indicated that OSER1-AS1 might be adopted as a hopeful diagnostic and therapeutic objective for RA.
35145919 The Gut Microbiome and Metabolites Are Altered and Interrelated in Patients With Rheumatoi 2021 The relationship among the gut microbiome, global fecal metabolites and rheumatoid arthritis (RA) has not been systematically evaluated. In this study, we performed 16S rDNA sequencing and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based nontargeted metabolomic profiling on feces of 26 untreated RA patients and 26 healthy controls. Twenty-six genera and forty-one MS2-identified metabolites were significantly altered in the RA patients. Klebsiella, Escherichia, Eisenbergiella and Flavobacterium were more abundant in the RA patients, while Fusicatenibacter, Megamonas and Enterococcus were more abundant in the healthy controls. Function prediction analysis demonstrated that the biosynthesis pathways of amino acids, such as L-arginine and aromatic amino acids, were depleted in the RA group. In the metabolome results, fecal metabolites including glycerophospholipids (PC(18:3(9Z,12Z,15Z)/16:1(9Z)), lysoPE 19:1, lysoPE 18:0, lysoPC(18:0/0:0)), sphingolipids (Cer(d18:0/16:0), Cer(d18:0/12:0), Cer(d18:0/14:0)), kynurenic acid, xanthurenic acid and 3-hydroxyanthranilic acid were remarkably altered between the RA patients and healthy controls. Dysregulation of pathways, such as tryptophan metabolism, alpha-linolenic acid metabolism and glycerophospholipid metabolism, may contribute to the development of RA. Additionally, we revealed that the gut microbiome and metabolites were interrelated in the RA patients, while Escherichia was the core genus. By depicting the overall landscape of the intestinal microbiome and metabolome in RA patients, our study could provide possible novel research directions regarding RA pathogenesis and targeted therapy.
35382860 Serum IGF-1 in patients with rheumatoid arthritis: correlation with disease activity. 2022 Apr 5 OBJECTIVE: Insulin-like growth factor (IGF)-1 participates in modulating immunity and inflammation. Its bioactivity is controlled by six IGF-binding proteins (IGFBP-1 to IGFBP-6). In particular, the IGFBP-3 level is reportedly linked to the disease activity of rheumatoid arthritis (RA), consistent with our previous study. Therefore, the present study aimed to reproduce the previous results. RESULTS: The serum IGFBP-3 level was not significantly different among the three groups according to disease activity based on the DAS28-ESR/CRP (p > 0.05) but was significantly different between the low- and high-disease-activity groups based on the DAS28-CRP (p = 0.036). Meanwhile, the interleukin-6 (IL-6) level moderately correlated with DAS28-CRP (Spearman's rho = 0.583, p < 0.001).
35628640 The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis. 2022 May 23 Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNFα production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)(2) fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to FcγR and to trigger TNFα release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylation and galactosylation levels of ACPA-IgG negatively correlate with inflammation-related parameters such as CRP, ESR, and RF. Functional assays show that dimerized ACPA-IgG significantly enhances TNFα release in an FcγRI-dependent manner, whereas healthy IgG does not. TNFα production inversely correlates with the relative intensities of the G0 glycoform, which lacks galactose and terminal sialic acid moieties.
35367240 Underpinning IL-6 biology and emphasizing selective JAK blockade as the potential alternat 2022 Jun 1 Interleukin 6 (IL-6), a pleiotropic inflammatory cytokine, is produced transiently due to tissue damage and infections. Nonetheless, IL-6 contributes to the host regenerative defense mechanism via classical signaling at the basal physiological level. Although tightly regulated transcriptional and post-transcriptional mechanism modulates its expression, dysregulated continual production of IL-6 during inflammatory conditions negatively affects immune cells. Molecular evidence has substantiated the pernicious out-turn of IL-6 trans-signaling in developing one such autoimmune joint disorder, rheumatoid arthritis (RA). Significantly increased levels of IL-6 in RA, along with multiple growth factors mainly released by synovial-like fibroblasts (FLS) and macrophages, is crucial for clinical disease progression. Due to its pathogenicity, in mediating inflammation and context-driven signaling cassette, blockade of IL-6 could be a potent target in the therapeutic intervention of RA. The clinical trials of various humanized IL-6 and anti-IL-6 receptor antibodies have proved their efficacy. However, severe side effects like neutropenia, thrombocytopenia, and abnormal liver enzymes contributed to dysfunctional adaptive immunity. The JAK-STAT pathway has been majorly implicated in RA disease progression upon IL-6 stimulation, simultaneously paving the path for innovative therapeutic approaches. JAK inhibitors, namely Tofacitinib, Baricitinib, Decernotinib, Upadacitinib, Peficitinib, and Filgotinib, have demonstrated clinical efficacy in recent decades as an alternative therapeutic strategy to abrogate IL-6 mediated aberrant activity in RA. This approach substitutes for the side effects incurred due to the IL-6 targeted therapies. This review discusses the history of research into IL-6 biology and therapies that target the IL-6 driven JAK/STAT pathway, including the successes, challenges, and drawbacks, emphasizing RA.
35606888 Effect of biological disease-modifying antirheumatic drugs on body composition in patients 2022 May 23 BACKGROUND: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. METHODS: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. RESULTS: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI - 5.58, 5.82), BMI 0.08 kg/m(2) (95% CI - 1.76, 1.92), FM - 0.08 kg (95% IC - 5.31, 5.14), and FFM - 2.08 kg (95% CI - 7.37, 3.21). CONCLUSION: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. TRIAL REGISTRATION: PROSPERO code: CRD42020206949.
35261304 Trans ethosomal hybrid composites of naproxen-sulfapyridine in hydrogel carrier: anti-infl 2022 Dec Current treatment for Rheumatoid arthritis (RA) utilizes Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs or its combination, to decrease joint inflammation. In the present study, naproxen (NAP) and sulfapyridine (SULF) ethosomes were prepared by a thin-film hydration technique using PL90G and cholesterol, later crosslinked with carbopol®934. The ethosomes and ethosomal hydrogel were evaluated for rheological properties, physico-chemical analysis, in vitro and in vivo study. The results show, NAP and SULF ethosomes exhibited an average vesicle size between 251.1 ± 1.80-343.5 ± 3.23 nm and 269.0 ± 1.17-358.8 ± 1.22 nm, respectively, with good stability (zeta potential > 30 mV) and polydispersity index. Differential scanning calorimeter and Fourier transform infrared studies reveal no significant changes in the drug properties of ethosomes. Transmission electron microscopy analysis discloses spherical shape vesicles below 200 nm. The entrapment efficiency of NAP and SULF ethosomes was above 66%, and NAP-SULF ethosomes-hydrogel (EH) exhibited a sustained release effect (>8 h). In vivo studies on NAP-SULF EH shows significant inhibition of inflammation (84.63%), with less paw volume (0.1935 ± 0.08 ml) on induced arthritis Albino Wistar rats, (p < .01). NAP-SULF EH was stable at 25 °C ± 0.5 for 3-months. To conclude, a hybrid composite of NAP-SULF in hydrogel carrier prevents inflammation effectively, and could be novel for trans delivery of drugs in RA.
35273387 Effects of targeted therapies on bone in rheumatic and musculoskeletal diseases. 2022 May Generalized bone loss (osteoporosis) and fragility fractures can occur in rheumatic and musculoskeletal diseases including rheumatoid arthritis and spondyloarthritis (SpA; including ankylosing spondylitis and psoriatic arthritis). In addition, rheumatoid arthritis can involve localized, periarticular bone erosion and, in SpA, local (pathological) bone formation can occur. The RANK-RANKL-osteoprotegerin axis and the Wnt-β-catenin signalling pathway (along with its inhibitors sclerostin and Dickkopf 1) have been implicated in inflammatory bone loss and formation, respectively. Targeted therapies including biologic DMARDs and Janus kinase (JAK) inhibitors can stabilize bone turnover and inhibit radiographic joint damage, and potentially also prevent generalized bone loss. Targeted therapies interfere at various points in the mechanisms of local and generalized bone changes in systemic rheumatic diseases, and they effect biomarkers of bone resorption and formation, bone mass and risk of fragility fractures. Studies on the effects of targeted therapies on rates of fragility fracture are scarce. The efficacy of biologic DMARDs for arresting bone formation in axial SpA is debated. Improved understanding of the most relevant therapeutic targets and identification of important targeted therapies could lead to the preservation of bone in inflammatory rheumatic and musculoskeletal diseases.
34057706 The feasibility of high-resolution ultrasonography and MRI in diagnosing finger lesions. 2022 Jun PURPOSE: To evaluate the diagnostic performance of both ultrasonography and MRI findings in finger lesions. METHODS: This study was carried out on seventy symptomatic patients (53 females and 17 males). Their ages ranged from 6 to 64 years. All patients were referred to the diagnostic radiology department from various outpatient clinics of general, orthopedic, cosmetic surgeries and rheumatology. All patients were subjected to history taking, clinical examination, laboratory investigations for rheumatoid arthritis patients and radiological investigations. Whenever we had a surgical and pathological final diagnosis, it was considered the gold standard of the results. When only ultrasound and MRI were correlated, MRI was considered the gold standard. RESULTS: In our study, we found that ultrasonography is useful for evaluating a variety of lesions of the finger. Its widespread availability, relatively low cost, and high spatial resolution make it an excellent tool for investigating finger disorders. MR is the best imaging modality for lesion characterization. By systematically using clinical history, lesion location, findings on radiographs and MR imaging features, the radiologist can differentiate between determinate and indeterminate lesions. CONCLUSION: We concluded that ultrasonography and MRI are complementary to reach a correct diagnosis in different etiologies of finger lesions.
35563556 Revealing the Immune Heterogeneity between Systemic Lupus Erythematosus and Rheumatoid Art 2022 May 5 The pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are greatly influenced by different immune cells. Nowadays both T-cell receptor (TCR) and B-cell receptor (BCR) sequencing technology have emerged with the maturity of NGS technology. However, both SLE and RA peripheral blood TCR or BCR repertoire sequencing remains lacking because repertoire sequencing is an expensive assay and consumes valuable tissue samples. This study used computational methods TRUST4 to construct TCR repertoire and BCR repertoire from bulk RNA-seq data of both SLE and RA patients' peripheral blood and analyzed the clonality and diversity of the immune repertoire between the two diseases. Although the functions of immune cells have been studied, the mechanism is still complicated. Differentially expressed genes in each immune cell type and cell-cell interactions between immune cell clusters have not been covered. In this work, we clustered eight immune cell subsets from original scRNA-seq data and disentangled the characteristic alterations of cell subset proportion under both SLE and RA conditions. The cell-cell communication analysis tool CellChat was also utilized to analyze the influence of MIF family and GALECTIN family cytokines, which were reported to regulate SLE and RA, respectively. Our findings correspond to previous findings that MIF increases in the serum of SLE patients. This work proved that the presence of LGALS9, PTPRC and CD44 in platelets could serve as a clinical indicator of rheumatoid arthritis. Our findings comprehensively illustrate dynamic alterations in immune cells during pathogenesis of SLE and RA. This work identified specific V genes and J genes in TCR and BCR that could be used to expand our understanding of SLE and RA. These findings provide a new insight inti the diagnosis and treatment of the two autoimmune diseases.
35236207 Patient-reported outcomes and realistic clinical endpoints for JAK inhibitors in rheumatoi 2022 Mar INTRODUCTION: Despite many effective therapeutics, health-related quality of life in RA remains low. Patients describe impacts of their disease in differing terms than health-care providers, stressing importance of pain, fatigue, poor sleep, and restrictions in work and social participation. AREAS COVERED: Patient-reported outcomes (PROs) across the phase 3 randomized controlled trials (RCTs) in RA with the JAK inhibitors (JAKis) are summarized. Patient populations, whether conventional synthetic disease modifying anti-rheumatic drug incomplete responders (csDMARD-IR) or biologic DMARD incomplete responders (bDMARD-IR) or csDMARD-naive, report differing baseline scores and placebo responses, generally lower in more treatment experienced patients. Improvements with all the approved JAKis in RA occur rapidly and are often maximal by 12-14 weeks, continuing thereafter. The rapidity of benefit reported by patients and convenience of oral administration often lead to increased adherence. EXPERT OPINION: A broad variety of PROs utilized in the RA RCTs with the JAKis confirm the clinical meaningfulness of their efficacy across treatment-experienced and naive populations. A majority of patients report statistically significant as well as clinically meaningful (≥ minimum clinically important differences, MCID) improvements, with numbers needed to treat (NNTs) ≤ 10 and scores ≥ normative values at endpoint, despite ≤ 12% reporting such scores at baseline.
35282807 Therapeutic Effect and Mechanism of Acupuncture in Autoimmune Diseases. 2022 Autoimmune diseases (AIDs) are conditions arising from abnormal immune reactions to autoantigens, which can be defined as the loss of immune tolerance to autoantigens, causing the production of autoantibodies and subsequent inflammation and tissue injury. The etiology of AIDs remains elusive, which may involve both genetic and environmental factors, such as diet, drugs, and infections. Despite rapid progress in the treatment of autoimmune diseases over the past few decades, there is still no approach that can cure AIDs. As an alternative approach, traditional Chinese medicine (TCM) such as acupuncture has been used in an attempt to treat AIDs including multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), and the results have proven to be quite promising, despite the fact that its mechanism is still not fully understood. In this review, the present knowledge regarding mechanisms of acupuncture in the treatment of AIDs has been summarized, and deeper insights will be provided in order to better understand how acupuncture may regulate immune responses during AIDs.
34808482 The protective effects of allopurinol against IL-17A-induced inflammatory response in mast 2022 Jan Rheumatoid arthritis (RA) is a common autoimmune disease in the elderly and it has been recently reported to be significantly associated with the activation of mast cells in joint tissues. IL-17A is a vital mediator that stimulates the activation of inflammation. Allopurinol is a classic agent for the suppression of uric acid production, recently reported to exert therapeutic effects on RA. In the present study, we investigated the regulatory effect of allopurinol against IL-17A-induced inflammatory response in mast cells and explored the potential mechanism of allopurinol on RA treatment. Firstly, we found that compared to normal synovium, IL-17A was significantly upregulated in the human RA synovium. IL-17A was used to stimulate an inflammatory state in mast cells in the absence or presence of allopurinol. We found that the production of inflammatory factors, PGE(2), and COX-2 was significantly elevated in IL-17A-treated mast cells, accompanied by the activation of the iNOS/NO axis and the elevated secretion of ROS. After treatment with allopurinol, the elevated inflammation, activated COX-2/PGE(2) and iNOS/NO axis, and oxidative stress were all dramatically alleviated. Mechanistically, the activated JNK/AP-1 and NF-κB pathways in IL-17A-treated mast cells were dramatically suppressed by the introduction of allopurinol. Taken together, our data reveal that allopurinol significantly alleviated the IL-17A-induced inflammatory response in mast cells.
35250992 The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A 2022 OBJECTIVES: To evaluate the safety of each anti-TNF therapy for patients with rheumatoid arthritis (RA) and then make the best choice in clinical practice. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library. The deadline for retrieval is August 2021. The ORs, Confidence Intervals (CIs), and p values were calculated by STATA.16.0 software for assessment. RESULT: 72 RCTs involving 28332 subjects were included. AEs were more common with adalimumab combined disease-modifying anti-rheumatic drugs (DMARDs) compared with placebo (OR = 1.60, 95% CI: 1.06, 2.42), DMARDs (1.28, 95% CI: 1.08, 1.52), etanercept combined DMARDs (1.32, 95% CI: 1.03, 1.67); certolizumab combined DMARDs compared with placebo (1.63, 95% CI: 1.07, 2.46), DMARDs (1.30, 95% CI: 1.10, 1.54), etanercept combined DMARDs (1.34, 95% CI: 1.05, 1.70). In SAEs, comparisons between treatments showed adalimumab (0.20, 95% CI: 0.07, 0.59), etanercept combined DMARDs (0.39, 95% CI: 0.15, 0.96), golimumab (0.19, 95% CI: 0.05, 0.77), infliximab (0.15, 95% CI: 0.03,0.71) decreased the risk of SAEs compared with golimumab combined DMARDs. In infections, comparisons between treatments showed adalimumab combined DMARDs (0.59, 95% CI: 0.37, 0.95), etanercept (0.49, 95% CI: 0.28, 0.88), etanercept combined DMARDs (0.56, 95% CI: 0.35, 0.91), golimumab combined DMARDs (0.51, 95% CI: 0.31, 0.83) decreased the risk of infections compared with infliximab combined DMARDs. No evidence indicated that the use of TNF-α inhibitors influenced the risk of serious infections, malignant tumors. CONCLUSION: In conclusion, we regard etanercept monotherapy as the optimal choice for RA patients in clinical practice when the efficacy is similar. Conversely, certolizumab + DMARDs therapy is not recommended. SYSTEMATIC REVIEW REGISTRATION: identifier PROSPERO CRD42021276176.
34398259 Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid 2022 Apr This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.
35603148 Proteome Profiling Identifies Serum Biomarkers in Rheumatoid Arthritis. 2022 Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein-protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8(+)T cell, and natural killer cell in the pathological mechanism, which can be better utilized for future research on RA. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.
34625402 Splicing machinery is impaired in rheumatoid arthritis, associated with disease activity a 2022 Jan OBJECTIVES: To characterise splicing machinery (SM) alterations in leucocytes of patients with rheumatoid arthritis (RA), and to assess its influence on their clinical profile and therapeutic response. METHODS: Leucocyte subtypes from 129 patients with RA and 29 healthy donors (HD) were purified, and 45 selected SM elements (SME) were evaluated by quantitative PCR-array based on microfluidic technology (Fluidigm). Modulation by anti-tumour necrosis factor (TNF) therapy and underlying regulatory mechanisms were assessed. RESULTS: An altered expression of several SME was found in RA leucocytes. Eight elements (SNRNP70, SNRNP200, U2AF2, RNU4ATAC, RBM3, RBM17, KHDRBS1 and SRSF10) were equally altered in all leucocytes subtypes. Logistic regressions revealed that this signature might: discriminate RA and HD, and anti-citrullinated protein antibodies (ACPAs) positivity; classify high-disease activity (disease activity score-28 (DAS28) >5.1); recognise radiological involvement; and identify patients showing atheroma plaques. Furthermore, this signature was altered in RA synovial fluid and ankle joints of K/BxN-arthritic mice. An available RNA-seq data set enabled to validate data and identified distinctive splicing events and splicing variants among patients with RA expressing high and low SME levels. 3 and 6 months anti-TNF therapy reversed their expression in parallel to the reduction of the inflammatory profile. In vitro, ACPAs modulated SME, at least partially, by Fc Receptor (FcR)-dependent mechanisms. Key inflammatory cytokines further altered SME. Lastly, induced SNRNP70-overexpression and KHDRBS1-overexpression reversed inflammation in lymphocytes, NETosis in neutrophils and adhesion in RA monocytes and influenced activity of RA synovial fibroblasts. CONCLUSIONS: Overall, we have characterised for the first time a signature comprising eight dysregulated SME in RA leucocytes from both peripheral blood and synovial fluid, linked to disease pathophysiology, modulated by ACPAs and reversed by anti-TNF therapy.