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ID PMID Title PublicationDate abstract
34436562 The impact of education inequality on rheumatoid arthritis risk is mediated by smoking and 2022 May 5 OBJECTIVE: To estimate the causal relationship between educational attainment-as a proxy for socioeconomic inequality-and risk of RA, and quantify the roles of smoking and BMI as potential mediators. METHODS: Using the largest genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) study of genetically predicted educational attainment (instrumented using 1265 variants from 766 345 individuals) and RA (14 361 cases, 43 923 controls). We used two-step MR to quantify the proportion of education's effect on RA mediated by smoking exposure (as a composite index capturing duration, heaviness and cessation, using 124 variants from 462 690 individuals) and BMI (517 variants, 681 275 individuals), and multivariable MR to estimate proportion mediated by both factors combined. RESULTS: Each s.d. increase in educational attainment (4.2 years of schooling) was protective of RA (odds ratio 0.37; 95% CI: 0.31, 0.44). Higher educational attainment was also protective for smoking exposure (β = -0.25 s.d.; 95% CI: -0.26, -0.23) and BMI [β = -0.27 s.d. (∼1.3 kg/m2); 95% CI: -0.31, -0.24]. Smoking mediated 24% (95% CI: 13%, 35%) and BMI 17% (95% CI: 11%, 23%) of the total effect of education on RA. Combined, the two risk factors explained 47% (95% CI: 11%, 82%) of the total effect. CONCLUSION: Higher educational attainment has a protective effect on RA risk. Interventions to reduce smoking and excess adiposity at a population level may reduce this risk, but a large proportion of education's effect on RA remains unexplained. Further research into other risk factors that act as potentially modifiable mediators are required.
35494514 MiR-129-5p Inactivates NF-κB Pathway to Block Rheumatoid Arthritis Development via Target 2022 METHODS: The abundance of miR-129-5p was detected in the samples including normal tissues and RA tissues and cell lines including human fibroblast-like synoviocytes (hFLSs) and human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). The CCK-8 assay, flow cytometry, Transwell, and ELISA were used to observe the effects of miR-129-5p on the phenotype of RA-FLSs. Moreover, the potential targets of miR-129-5p were identified with TargetScan and dual-luciferase reporter gene assay. Besides, the abundances of the proteins were analyzed with western blot. RESULTS: Decreased miR-129-5p was observed in RA tissues and cells. Increased miR-129-5p obviously blocked the proliferation, inflammatory stress, and migration and remarkably promoted cellular apoptosis. Moreover, BRD4 was confirmed as targets of miR-129-5p, and BRD4 upregulation could partly rescue the inhibition of miR-129-5p on aggressive behaviors of RA-FLSs. Besides, the finding of this study also proved that upregulated miR-129-5p could impede the NF-κB pathway via targeting BRD4. CONCLUSION: This study suggests that miR-129-5p suppresses the activation of NF-κB pathway to block the progression of RA via targeting BRD4.
35069529 Overload of the Temporomandibular Joints Accumulates γδ T Cells in a Mouse Model of Rheu 2021 Recently, it has been reported that γδ T cells are associated with the pathology of rheumatoid arthritis (RA). However, there are many uncertainties about their relationship. In this study, we investigated the morphological and histological properties of peripheral as well as temporomandibular joints (TMJ) in a mouse model of rheumatoid arthritis with and without exposure to mechanical strain on the TMJ. Collagen antibody-induced arthritis (CAIA) was induced by administering collagen type II antibody and lipopolysaccharide to male DBA/1JNCrlj mice at 9-12 weeks of age, and mechanical stress (MS) was applied to the mandibular condyle. After 14 days, 3D morphological evaluation by micro-CT, histological staining (Hematoxylin Eosin, Safranin O, and Tartrate-Resistant Acid Phosphatase staining), and immunohistochemical staining (ADAMTS-5 antibody, CD3 antibody, CD45 antibody, RORγt antibody, γδ T cell receptor antibody) were performed. The lower jawbone was collected. The mandibular condyle showed a rough change in the surface of the mandibular condyle based on three-dimensional analysis by micro-CT imaging. Histological examination revealed bone and cartilage destruction, such as a decrease in chondrocyte layer width and an increase in the number of osteoclasts in the mandibular condyle. Then, immune-histological staining revealed accumulation of T and γδ T cells in the subchondral bone. The temporomandibular joint is less sensitive to the onset of RA, but it has been suggested that it is exacerbated by mechanical stimulation. Additionally, the involvement of γδ T cells was suggested as the etiology of rheumatoid arthritis.
35627350 Smoking Cessation Rates among Patients with Rheumatoid Arthritis and Osteoarthritis Follow 2022 May 10 (1) Background: Smoking cessation may be very difficult, even if smoking aggravates the prognosis of a disease, which has been shown to be the case for persons with rheumatoid arthritis (RA). In contrast, an association in patients with osteoarthritis (OA) is still disputed. The primary objective was to compare smokers diagnosed with RA and OA to controls, regarding smoking cessation rates after following the intensive 'Gold Standard programme' (GSP). Secondary objectives included the identification of significant prognostic factors for successful quitting. (2) Methods: In total, 24,652 patients were included in this prospective cohort study, after attending the national GSP for smoking cessation intervention 2006-2016, as registered in the Danish Smoking Cessation Database. Data were linked to the National Patient Register. Hereof, 227 patients (1%) were diagnosed with seropositive RA and 2899 (12%) with OA. Primary outcome was continuous abstinence six months after the planned quitting date. (3) Results: In total, 16,969 (69%) of the patients participated in the follow-up interviews. The adjusted odds ratios for successful quitting were similar to the control group for both RA (1.28, 95% CI: 0.90-1.80) and OA patients (0.92, 0.82-1.03). The outermost, strongest positive factor for successful quitting was compliance, defined as attending ≥75% of the meetings. To a lesser degree, attending an individual intervention was a positive predictor, while being heavy smokers, disadvantaged smokers, women, living with a smoker, and if GSP was recommended by health professionals were negative predictors. (4) Conclusions: The odds ratios for quitting were similar to controls for both RA and OR patients. Additional research is needed to determine effective actions towards increased attendance at the programmes.
35417127 Cytokine Regulation and Fast Inflammation Resolution in Early Rheumatoid Arthritis by Ceri 2022 Apr 27 Rheumatoid arthritis (RA) is an incurable chronic disorder that may induce autoinflammation and serious pain in the joints. Early diagnosis and treatment are important for RA prognosis. However, there is a lack of effective and objective diagnostic approaches. Levels of several immunity cytokines were found to change for patients with early RA, including IL-6, TNF-α, and IL-17 in serum. We assumed a combined change of these cytokines could predict early RA, and a total of 37 outpatients were found. After these patients with early symptoms had been followed for more than one year, 32 clinical cases of RA were diagnosed. The accuracy rate of the current method is >86%. We assumed the symptom relief could be achieved by regulating these cytokines and serum lipid-associated indicators. Thereafter, (R)-dihydrolipoic acid (R-DHLA)-stabilized gold nanoclusters (AuNCs) without (R-DHLA-AuNCs) and with cerium modification (R-DHLA-AuNCs-Ce) were employed for treatment of the RA rat model in vitro and in vivo. R-DHLA-AuNCs-Ce exhibited extraordinary reactive oxygen species-scavenging and anti-inflammation effects by regulating macrophage polarization, which was found to be more effective than methotrexate. The inflammation response of the joint microenvironment was also reduced with an exciting efficiency. By complex analysis of the pro-inflammatory cytokines and activity period indicators in vivo and in vitro, we concluded that macrophage-mediated inflammation exacerbated autoimmunity, which fully relieved the symptoms after administration of R-DHLA-AuNCs-Ce to RA rats.
34373933 Sequences of biological treatments for patients with moderate-to-severe rheumatoid arthrit 2022 Jan BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended to be added in sequentially in the treatment of moderate-to-severe rheumatoid arthritis (RA). All these drugs, however, are substantially more expensive than conventional synthetic DMARDs throughout the world, including in China. The objective of this study is to evaluate the cost-effectiveness of treatment sequences of bDMARDs for patients with moderate-to-severe rheumatoid arthritis from the Chinese healthcare system perspective. METHODS: An individual patient simulation model was used to track the course of patients from first treatment through switches to further lines in a sequence. The comparator treatment sequence commenced with methotrexate, followed by non-biologic therapy. The intervention sequences were assumed to be the combinations of bDMARDs available, followed by non-biologic therapy. Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated. Univariable and probabilistic sensitivity analyses and scenario analyses were performed to evaluate the model uncertainty. RESULTS: Compared with the comparator treatment sequence, bDMARDs sequences were associated with more life years, QALYs, and cost. These produced ICERs ranged from $27,441.36/QALY to $40,149.2/QALY, above the willingness-to-pay threshold of $10,378 per QALY. The uncertainty analyses and the scenario analyses confirmed the result of the base case analysis. CONCLUSIONS: From the perspective of the Chinese healthcare system, bDMARDs sequences are estimated not to be cost-effective compared with conventional synthetic disease-modifying antirheumatic drug strategy for patients with moderate-to-severe RA at a WTP threshold of $10,378 per QALY. Price reductions are warranted to make bDMARDs cost-effective and affordable.
34401906 Morning stiffness precedes the development of rheumatoid arthritis and associates with sys 2022 May 5 OBJECTIVES: Morning stiffness (MS) is characteristic of RA and associates with markers of systemic and local inflammation in RA patients. In patients with arthralgia, MS is a cardinal symptom to recognize arthralgia at-risk for RA development [i.e. clinically suspect arthralgia (CSA)]. In CSA, MS is also assumed to reflect inflammation, but this has never been studied. Therefore we aimed to study whether MS in CSA patients is associated with systemic and subclinical joint inflammation. METHODS: A total of 575 patients presenting with CSA underwent laboratory investigations and contrast-enhanced 1.5 T MRI of the hand and forefoot (scored according to the Rheumatoid Arthritis MRI Score method). Associations of MS (duration ≥60 min) with the presence of subclinical joint inflammation (synovitis, tenosynovitis and osteitis) and increased CRP (≥5 mg/l) were determined with logistic regression. Additionally, the effect of MS duration (≥30, ≥60 and ≥120 min) was studied. RESULTS: A total of 195 (34%) CSA patients experienced MS. These patients more often had subclinical synovitis [34% vs 21%; odds ratio (OR) 1.95 (95% CI 1.32, 2.87)], subclinical tenosynovitis [36% vs 26%; OR 1.59 (95% CI 1.10, 2.31)] and increased CRP [31% vs 19%; OR 1.93 (95% CI 1.30, 2.88)] than patients without MS. In multivariable analyses, subclinical synovitis [OR 1.77 (95% CI 1.16, 2.69)] and CRP [OR 1.78 (95% CI 1.17-2.69)] remained independently associated with MS. In CSA patients who later developed RA, and thus in retrospect were 'pre-RA' at the time of CSA, MS was more strongly associated with subclinical synovitis [OR 2.56 (95% CI 1.04, 6.52)] and CRP [OR 3.86 (95% CI 1.45, 10.24)]. Furthermore, associations increased with longer MS durations. CONCLUSION: Inflammation associates with MS in the CSA phase that preceded clinical arthritis. These results increase our understanding of MS when assessing arthralgia in clinical practice.
34210836 "It may help you to know…": The Early-phase Qualitative Development of a Rheumatoid Arth 2022 Feb OBJECTIVE: Treatment guidelines for rheumatoid arthritis (RA) include a patient-centered approach and shared decision making, which includes a discussion of patient goals. We describe the iterative early development of a structured goal elicitation tool to facilitate goal communication for persons with RA and their clinicians. METHODS: Tool development occurred in 3 phases: (1) clinician feedback on the initial prototype during a communication training session; (2) semistructured interviews with RA patients; and (3) community stakeholder feedback on elements of the goal elicitation tool in a group setting and electronically. Feedback was dynamically incorporated into the tool. RESULTS: Clinicians (n = 15) and patients (n = 10) provided feedback on the tool prototypes. Clinicians preferred a shorter tool deemphasizing goals outside of their perceived treatment domain or available resources; they highlighted the benefits of the tool to facilitate conversation but raised concerns regarding current constraints of the clinic visit. Patients endorsed the utility of such a tool to support agenda setting and preparing for a visit. Clinicians, patients, and community stakeholders reported the tool was useful but identified barriers to implementation that the tool could itself resolve. CONCLUSION: A goal elicitation tool for persons with RA and their clinicians was iteratively developed with feedback from multiple stakeholders. The tool can provide a structured way to communicate patient goals within a clinic visit and help overcome reported barriers such as time constraints. Incorporating a structured communication tool to enhance goal communication and foster shared decision making may lead to improved outcomes and higher-quality care in RA.
33687525 Placebo and nocebo responses in randomized controlled trials of Janus kinase inhibitor mon 2022 Jun OBJECTIVE: The goal of this meta-analysis was to assess the frequency and magnitude of placebo and nocebo responses in placebo-controlled randomized controlled trials (RCTs) of Janus kinase (JAK) inhibitor monotherapy for rheumatoid arthritis (RA) METHODS: We performed a meta-analysis on the rates of placebo response, adverse effects (AEs), severe AEs (SAEs) and withdrawal due to AEs in placebo-controlled randomized clinical trials (RCTs) of JAK inhibitor therapy for RA. RESULTS: Five RCTs contained a total of 1422 patients (746 trial participants and 676 controls). The pooled incidence of an American College of Rheumatology 20% (ACR20) response rate was 33.0% (95% CI 19.6-44.9%) in placebo-treated patients and 68.3% (95% CI 61.4-74.1%) in active drug-treated patients. A strong negative correlation was observed between drug efficacies (ACR20 response) and AE rates in the placebo arm, indicating that the stronger the placebo response, the weaker the nocebo response (r = -0.906, P = 0.034). The pooled estimate of at least one AE was 54.1% (95% CI 44.6-63.4%) in placebo-treated patients and 54.5% (95% CI 46.2-62.6%) in active drug-treated patients. The pooled SAE rate was 3.9% (95% CI 2.7-5.7%) in placebo-treated patients and 3.8% (95% CI 2.5-5.7%) in active comparator-treated patients. The pooled estimate of withdrawal owing to an AE was 4.1% (95% CI 1.4-11.3%) in placebo-treated patients and 2.1% (95% CI 0.8-5.4%) in active drug-treated patients. However, there were no differences in the pooled risk of AE, SAEs, or withdrawal owing to AEs between the active comparator and placebo groups. A strong positive correlation was observed in AE rates between the placebo and active arms, indicating that the stronger the nocebo response, the higher the AE rate in the active arm (r = 0.957, P = 0.012). CONCLUSION: The frequency of placebo and nocebo responses was 33.0 and 54.1%, respectively, in JAK monotherapy trials for RA. The findings indicated that the strengths of placebo and nocebo responses are inversely proportional and that clinically significant differences were absent between AE, SAE, and dropout owing to AEs.
35432322 Natural Killer Cells Infiltration in the Joints Exacerbates Collagen-Induced Arthritis. 2022 INTRODUCTION: The role of natural killer (NK) cells in rheumatoid arthritis remains controversial. We aimed to assess the role of NK cells in the pathogenesis of rheumatoid arthritis. MATERIALS AND METHODS: The percentage of NK cells in the peripheral blood, spleen, lymph nodes and inflamed paws from collagen-induced arthritis mice were examined through the disease progression. Correlation between the proportion of NK cells and subsets with arthritis score, histopathological changes, and bone destruction were evaluated. Adoptive cell transfer was performed to determine the effect of NKp46(+)NK cells on arthritis development, and the role of receptor NKp46 was explored with NKp46 knockout mice. RESULTS: The percentage of NK cells in peripheral blood decreased at the late stage of the disease and negatively correlated with arthritis score. NK cells increased in the inflamed paws during arthritis development and were positively associated with arthritis score, histopathological change, and bone destruction. Adoptive transfer of NKp46(+)NK cells before disease onset resulted in increased NK cells infiltration in the joints, higher incidence of arthritis, more severe clinical symptoms, and more pronounced joint inflammation and bone damage. NKp46 deficiency had no significant influence on the incidence and severity of arthritis in collagen-induced arthritis mice. CONCLUSIONS: NK cell infiltration in the joints positively correlates with arthritis progression, inflammation, and bone destruction. The pathogenic role of NK cells in rheumatoid arthritis may be independent of the receptor NKp46.
35443431 Study of Cardiovascular Involvement in Rheumatoid Arthritis and it's Correlation with Seve 2022 Apr Rheumatoid arthritis is a chronic systemic disease of unknown ethology characterised by persistent inflammatory synovitis usually affecting peripheral joints with symmetric distribution. Most common cause of death in RA is cardiovascular disease and pericarditis is the most common form of cardiac involvement. Valvular disorders, coronary vasculitis and ventricular diastolic dysfunction can be seen. The aim and objective was to study the prevalence of cardiovascular involvement in the patients of RA and correlate the cardiovascular involvement with duration and severity of disease. MATERIAL: The present study was conducted in the Rheumatology Division of department of medicine Sardar Patel medical college Bikaner. It's a cross sectional study done on 100 consecutive patients, diagnosed with RA according to ACR-EULAR classification criteria for RA 2010. Patients with history of smoking, renal failure, diabetes, hypertension, pregnancy, thyroid dysfunction and other systemic diseases were excluded. CBC, DLC, rheumatoid factor, ESR, C-Reactive protein, Anti-CCP antibody, LFT, RFT, Blood glucose, lipid profile and thyroid profile was done on the patients. Electrocardiography and ECHOCARDIOGRAM were also done. For statistical analysis SPSS17 for windows, standard version was used. OBSERVATION: We observed in our study that a large number of RA patients had ECG (38%) and ECHO (32%) abnormalities. We found that Polyarthritis was the most common symptom (63%) while Dyspnoea (25%) and chest pain (16%) were the most common cardiovascular symptoms. Patients who had bradycardia, heart block and P-pulmonale in ECG were likely to have severe RA. In our study patients with longer duration of disease had more chances of VPCs in ECG. LVH and T-wave inversion in lead ll, lll and aVF were found to be significantly associated with duration of treatment. Patients who had dilated left atrium in ECHO were more likely to have severe disease. Longer duration of treatment was associated with ECHO finding of concentric LVH. As the age increases, prevalence of T wave changes also increases. CONCLUSION: This study indicates the high prevalence of cardiac involvement in RA patients, so early detection of cardiac involvement (using ECG, echocardiography, etc.) may reduce the morbidity and mortality.
35022034 Healthcare professionals' perceptions on barriers and facilitators to DMARD use in rheumat 2022 Jan 13 BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of rheumatoid arthritis (RA) treatment. However, the full benefits of DMARDs are often not realized because many patients are sub-optimally adherent to their medication. In order to optimize adherence, it is essential that healthcare professionals (HCPs) understand patients' barriers and facilitators for medication use. Insight in these barriers and facilitators may foster the dialogue about adequate medication use between HCPs and patients. What HCPs perceive as barriers and facilitators has, so far, scarcely been investigated. This study aimed to identify the perceptions of HCPs on patients' barriers and facilitators that might influence their adherence. METHODS: This qualitative study was performed using semi structured in-depth interviews with HCPs. An interview guide was used, based on an adjusted version of the Theoretical Domains Framework (TDF). Thematic analysis was conducted to identify factors that influence barriers and facilitators to DMARD use according to HCPs. RESULTS: Fifteen HCPs (5 rheumatologists, 5 nurses and 5 pharmacists) were interviewed. They mentioned a variety of factors that, according to their perceptions, influence DMARD adherence in patients with RA. Besides therapy-related factors, such as (onset of) medication effectiveness and side-effects, most variation was found within patient-related factors and reflected patients' beliefs, ways of coping, and (self-management) skills toward medication and their condition. In addition, factors related to the condition (e.g., level of disease activity), healthcare team and system (e.g., trust in HCP), and social and economic context (e.g. support, work shifts) were reported. CONCLUSIONS: This study provided insights in HCPs' perceptions of the barriers and facilitators to DMARD use patients with RA. Most factors that were mentioned were patient-related and potentially modifiable. When physicians understand patients' perceptions on medication use, adherence to DMARDs can probably be optimized in patients with RA leading to more effectiveness of treatment outcomes.
34864016 Associations of blood and urinary heavy metals with rheumatoid arthritis risk among adults 2022 Feb Heavy metals exposure has been widely recognized as a risk factor for human health. However, limited information is available about the impacts of heavy metals on rheumatoid arthritis (RA). Herein, we estimated the associations of 3 blood and 11 urinary metals with the risk of RA among 49830 U.S. adults from the National Health and Nutrition Examination Survey (NHANES), 1999-2018. In the single-exposure model, blood cadmium (Cd) and lead (Pb), urinary Cd, Pb, antimony (Sb), tungsten (Tu), and uranium (Ur) were identified to be positively associated with RA risk. Furthermore, weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) analyses consistently showed that both blood and urinary metals-mixed exposure were positively correlated with the risk of RA, and highlighted that Cd and Pb were responsible for the outcomes. Such associations were more evident in the young and middle-aged population. These findings indicated that exposure to heavy metals increased RA risk, and advanced the identification of risk factors for RA.
33769451 Long-term persistence of rituximab in patients with rheumatoid arthritis: an evaluation of 2022 Feb 2 OBJECTIVES: B cell depletion therapy based on rituximab in patients with RA was pioneered at University College London Hospitals/University College London in 1998. The objective of this study was to evaluate long-term persistence of rituximab and identify factors associated with discontinuation of treatment. METHODS: Retrospective review of medical records from all rituximab-treated RA patients followed up in a dedicated clinic (1998-2020). Data collected included gender, disease duration, previous DMARDs, autoantibody status, age and concomitant therapy at first cycle, length of follow-up, and number of cycles. Drug survival and factors associated with drug discontinuation were analysed using Kaplan-Meier survival curves, log-rank test and Cox regression analysis. RESULTS: A total of 404 patients were included. Median disease duration and age at time of first rituximab cycle were 10 and 57 years, respectively. Median total follow-up was 55 months and median number of cycles five. 93.1% of patients were seropositive. Overall, 31.2% of patients stopped rituximab, with the largest reason for discontinuing being primary inefficacy (42.1%). Comparison of Kaplan-Meier curves showed that rituximab drug survival was lower in seronegative patients and in patients who had previously failed at least one biologic DMARD (bDMARD). Cox regression analysis revealed that rituximab discontinuation was associated with a greater number of previous bDMARDs. CONCLUSION: Many patients with RA achieve good control of their disease with repeated cycles of rituximab treatment. The most common reasons for treatment discontinuation were either primary or secondary inefficacy. Patients who were seronegative and who had previously failed other bDMARDs were more at risk of drug discontinuation.
35140805 Prediction of New Risk Genes and Potential Drugs for Rheumatoid Arthritis from Multiomics 2022 Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease for which there is a lack of therapeutic options. Genome-wide association studies (GWASs) have identified over 100 genetic loci associated with RA susceptibility; however, the most causal risk genes (RGs) associated with, and molecular mechanism underlying, RA remain unknown. In this study, we collected 95 RA-associated loci from multiple GWASs and detected 87 candidate high-confidence risk genes (HRGs) from these loci via integrated multiomics data (the genome-scale chromosome conformation capture data, enhancer-promoter linkage data, and gene expression data) using the Bayesian integrative risk gene selector (iRIGS). Analysis of these HRGs indicates that these genes were indeed, markedly associated with different aspects of RA. Among these, 36 and 46 HRGs have been reported to be related to RA and autoimmunity, respectively. Meanwhile, most novel HRGs were also involved in the significantly enriched RA-related biological functions and pathways. Furthermore, drug repositioning prediction of the HRGs revealed three potential targets (ERBB2, IL6ST, and MAPK1) and nine possible drugs for RA treatment, of which two IL-6 receptor antagonists (tocilizumab and sarilumab) have been approved for RA treatment and four drugs (trastuzumab, lapatinib, masoprocol, and arsenic trioxide) have been reported to have a high potential to ameliorate RA. In summary, we believe that this study provides new clues for understanding the pathogenesis of RA and is important for research regarding the mechanisms underlying RA and the development of therapeutics for this condition.
35126375 A Novel Humanized Anti-Interleukin-6 Antibody HZ0408b With Anti-Rheumatoid Arthritis Thera 2021 Interleukin-6 (IL-6), a pleiotropic cytokine that regulates immune responses and inflammatory reactions, plays a pivotal role in the development of rheumatoid arthritis (RA). Blockade of IL-6 signaling with the monoclonal antibody (mAb) represents an important advancement in RA treatment. Although two IL-6 receptor antibodies are already available in the clinic, there is no mAb specifically targeting the human IL-6 to block IL-6 signaling for RA treatment. In this study, we have developed a novel humanized anti-IL-6 mAb HZ-0408b with potent binding and neutralizing activity to human IL-6. We demonstrated that HZ-0408b has a high species specificity and low cross-reactivity. Moreover, HZ-0408b showed a more potent inhibitory effect on IL-6 signaling than Siltuximab, an FDA-approved anti-IL-6 chimeric mAb. HZ-0408b is comparable to Olokizumab, a humanized mAb against IL-6 that is already in phase III studies. We observed that HZ-0408b is well tolerated at doses that can achieve therapeutic serum levels in cynomolgus monkey. Most importantly, we proved that HZ-0408b treatment significantly ameliorated joint swelling after the onset of arthritis and dramatically reduced plasma C-reactive protein (CRP) levels in a monkey collagen-induced arthritis (CIA) model. Collectively, our findings using non-human primates indicate that humanized anti-IL-6 mAb HZ-0408b has excellent safety and efficacy profiles for RA therapy.
34958010 Preoperative erythrocyte sedimentation rate in patients with rheumatoid arthritis predicts 2022 PURPOSE: To thoroughly evaluate preoperative risk factors for deep venous thrombosis (DVT) in patients with knee rheumatoid arthritis (RA) undergoing unilateral total knee arthroplasty (TKA). METHODS: Clinical data of 106 patients with knee RA who underwent unilateral TKA from August 2014 to October 2020 were collected. All patients received ultrasonic examination of the veins of both lower extremities on the third day after TKA and were divided into DVT and non-DVT groups. The associations between age, gender, body mass index (BMI), history of diabetes/hypertension, common serum lipid levels, indicators related to coagulation function, blood viscosity, erythrocyte sedimentation rate (ESR) and postoperative DVT were statistically compared and analyzed. RESULTS: ESR was significantly correlated with DVT risk after TKA (OR = 1.844, 95% CI = 1.022-2.981, P = 0.019). Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off point of ESR for predicting DVT was 42 mm/h with a sensitivity of 95.5% and specificity of 66.7%. CONCLUSION: An increased preoperative ESR value is a risk factor for DVT in patients with knee RA following unilateral TKA. Pre-surgery control of ESR level and prevention of postoperative DVT in these patients are worthy of attention.
34544951 A Rare Case of Rheumatoid Arthritis with Tocilizumab-induced Intestinal Mucosal Injury. 2022 Apr 1 Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis.
33635234 Identification of circulating miR-22-3p and let-7a-5p as novel diagnostic biomarkers for r 2022 Jan OBJECTIVES: Early and correct diagnosis would be beneficial for outcomes of rheumatoid arthritis (RA), but there are some limitations in current diagnostic tools. In this study, we aimed to evaluate the diagnostic value of circulating miR-22-3p and let-7a-5p in RA. METHODS: Seventy-six RA patients, 30 systemic lupus erythematosus patients, 32 Sjögren's syndrome patients and 36 healthy donors recruited at the First Affiliated Hospital of Fujian Medical University (China) were included in this study. Circulating miR-22-3p and let-7a-5p in plasma were measured using reverse transcriptase quantitative PCR and serum cytokines were detected by cytometric bead array. The participants' clinical materials were also collected. Receiver operating characteristic curve analysis and correlation analysis were performed to assess the potential value of circulating miRNAs in RA. RESULTS: Circulating miR-22-3p and let-7a-5p are significantly increased in RA patients and able to distinguish RA patients from other populations. Circulating let-7a-5p has been shown to improve the diagnostic ability of current laboratory indicators anti-cyclic citrullinated peptide antibodies and rheumatoid factor. Moreover, the discriminatory capacity of both circulating miRNAs contribute to complement the diagnosis for seronegative RA. Meanwhile, correlation analysis reveals that circulating miR-22-3p positively correlates with haemoglobin, serum bilirubin, albumin and IL-17 but negatively correlates with mean platelet volume as well as let-7a-5p. CONCLUSIONS: The increased circulating miR-22-3p and let-7a-5p levels in RA patients, especially in seronegative RA patients, may provide potential promising diagnostic biomarkers for RA in clinical practice.
35434133 Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potentia 2022 AIMS: This study is aimed at investigating the pathogenesis of rheumatoid arthritis (RA) by identifying key biomarkers, associated immune infiltration, and small-molecule compounds using bioinformatic analysis. METHODS: Six datasets were obtained from the Gene Expression Omnibus database, and the batch effect was adjusted. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse differentially expressed genes (DEGs). Furthermore, candidate small-molecule drugs associated with RA were selected from the Connectivity Map (CMap) database. The least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and multivariate logistic regression analyses were performed on DEGs to screen for RA diagnostic markers. The receiver operating characteristic curve, concordance index, and GiViTi calibration band were the metrics used to assess the diagnostic markers of RA identified in this analysis. The single-sample gene set enrichment analysis was performed to calculate the scores of infiltrating immune cells and evaluate the activities of immune-related pathways. Finally, the correlation between screening markers and RA diagnosis was determined. RESULTS: A total of 227 DEGs were identified. Functional enrichment analysis and KEGG revealed that DEGs were enriched by the immune response. CMap analysis identified 11 small-molecule compounds with therapeutic potential for RA. In gene expression, the activities of 13 immune cells and 12 immune-related pathways significantly differed between patients with RA and healthy controls. DPYSL3 and SPP1 had the potential to diagnose RA. SPP1 expression was positively correlated with DPYSL3 in 11 immune cells and 10 immune-related pathways. CONCLUSION: This study comprehensively analysed DEGs and immune infiltration and screened for potential diagnostic markers and small-molecule compounds of RA.