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ID PMID Title PublicationDate abstract
34229736 Machine learning model for identifying important clinical features for predicting remissio 2021 Jul 6 BACKGROUND: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI). METHODS: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at 1-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions. RESULTS: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8-72.9% and 0.511-0.694, respectively. The Shapley plot in XAI showed that the impacts of the variables on predicting remission differed for each bDMARD. The most important features were age for adalimumab, rheumatoid factor for etanercept, erythrocyte sedimentation rate for infliximab and golimumab, disease duration for abatacept, and C-reactive protein for tocilizumab, with mean SHAP values of - 0.250, - 0.234, - 0.514, - 0.227, - 0.804, and 0.135, respectively. CONCLUSIONS: Our proposed machine learning model successfully identified clinical features that were predictive of remission in each of the bDMARDs. This approach may be useful for improving treatment outcomes by identifying clinical information related to remissions in patients with rheumatoid arthritis.
34458379 Systemic Proteomic Analysis Reveals Distinct Exosomal Protein Profiles in Rheumatoid Arthr 2021 OBJECTIVE: Rheumatoid arthritis (RA) is a complex disease with unknown pathogenesis. In recent years, fewer have paid attention to the broad spectrum of systemic markers of RA. The aim of this study was to identify exosomal candidate proteins in the pathogenesis of RA. METHODS: Totally, 12 specimens of plasma from 6 RA patients and 6 age- and gender-matched controls from the Chinese population were obtained for nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis to identify exosomal profiles. RESULTS: A total of 278 exosomal proteins were detected. Among them, 32 proteins were significantly upregulated (FC ≥ 2.0 and P < 0.05) and 5 proteins were downregulated (FC ≤ 0.5 and P < 0.05). Bioinformatics analysis revealed that transthyretin (TTR), angiotensinogen (AGT), lipopolysaccharide-binding protein (LBP), monocyte differentiation antigen CD14 (CD14), cartilage oligomeric matrix protein (COMP), serum amyloid P (SAP/APCS), and tenascin (TNC) can interact with each other. Subsequently, these cross-linked proteins may be mainly involved in the inflammatory-related pathways to mediate the onset of RA. Noteworthy, the LBP/CD14 complex can promote the expression of IL-8 and TNF-α, eventually leading to the development of RA. CONCLUSIONS: Our findings suggest distinct plasmatic exosomal protein profiles in RA patients. These proteins not only take important parts in the vicious circle in the pathogenic process of RA but also serve as novel biomarkers in RA diagnosis and prognosis.
32934120 Evaluating Quality of Care for Rheumatoid Arthritis for the Population of Alberta Using Sy 2021 Apr OBJECTIVE: We evaluated 4 national rheumatoid arthritis (RA) system-level performance measures (PM) in Alberta, Canada. METHODS: Incident and prevalent RA cases ≥ 16 years of age since 2002 were identified using a validated case definition applied in provincial administrative data. Performance was ascertained through analysis of health data between fiscal years 2012/13-2015/16. Measures evaluated were as follows: proportion of incident RA cases with a rheumatologist visit within 1 year of first RA diagnosis code (PM1); proportion of prevalent RA patients who were dispensed a disease-modifying antirheumatic drug (DMARD) annually (PM2); time from first visit with an RA code to DMARD dispensation and proportion of incident cases where the 14-day benchmark for dispensation was met (PM3); and proportion of patients seen in annual follow-up (PM4). RESULTS: There were 31,566 prevalent and 2730 incident RA cases (2012/13). Over the analysis period, the proportion of patients seen by a rheumatologist within 1 year of onset (PM1) increased from 55% to 63%; however, the proportion of RA patients dispensed DMARD annually (PM2) remained low at 43%. While the median time to DMARD from first visit date in people who received DMARD improved over time from 39 days to 28 days, only 38-41% of patients received treatment within the 14-day benchmark (PM3). The percentage of patients seen in yearly follow-up (PM4) varied between 73-80%. CONCLUSION: The existing Alberta healthcare system for RA is suboptimal, indicating barriers to accessing specialty care and treatment. Our results inform quality improvement initiatives required within the province to meet national standards of care.
33687217 Nanoemulsions Target to Ectopic Lymphoids in Inflamed Joints to Restore Immune Tolerance i 2021 Mar 24 Inducing immune tolerance through repeated administration of self-antigens is a promising strategy for treating rheumatoid arthritis (RA), and current research indicates that coadministration of immunomodulators can further orchestrate the tolerogenic response. However, most of the clinical trials based on tolerance induction have negligible therapeutic effects. Peripheral lymphoid organs play critical roles in immunotherapy. Here, we design an engineered nanoemulsion for targeted codelivery of self-antigens and an immunomodulator to ectopic lymphoid structures (ELSs) in inflamed joints of RA. Namely, a citrullinated multiepitope self-antigen (CitP) and rapamycin are incorporated into the nanoemulsions (NEs@CitP/Rapa), which are fabricated by a facial method using commercialized pharmaceutical excipients. After intravenous administration, the nanoemulsion shows satisfactory accumulation in the inflamed paws and provides enhanced anti-inflammatory effect in various experimental murine models of RA. Our study provides a promising targeting strategy to induce immune tolerance for the treatment of RA.
34227067 Iron metabolism in patients with rheumatoid arthritis. 2021 Jun OBJECTIVE: Anemia is the hematological issue that occurs most often as a manifestation in RA. The aim of the study was to assess iron deficiency in RA patients. PATIENTS AND METHODS: The study was carried out on 62 RA patients treated between 2016 and 2017. RESULTS: A higher percentage of RA patients compared to the control group had TSAT below 20% (43% vs. 5%), ferritin below the reference range (15% vs. 7%), sTfR above 1.59 mg/l (26% vs. 0%) and hepcidin below 14.5 ng/ml (56% vs. 2%). 60% of RA patients had iron deficiency, and 18% - anemia. Correlations were found between reduced levels of ferritin and patients being younger, female, with lower GGT and higher platelet counts. Correlations were also found between iron deficiency and patients being younger, female, having reduced hemoglobin, increased platelet counts, increased GFR, reduced GGT, lower disease activity, and less frequent use of sulfasalazine. CONCLUSIONS: Iron deficiency is common (64%) in RA patients where there is high disease activity. RA patients had lower transferrin, lower ferritin, lower hepcidin, and higher sTfR. Decreased DAS-28 and reduced hemoglobin were the strongest determinants of iron deficiency.
34894777 Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheu 2021 Dec PURPOSE OF REVIEW: Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes. DESIGNS: To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied. RESULTS: In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive. CONCLUSION: This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.
34627335 Machine learning-based prediction model for responses of bDMARDs in patients with rheumato 2021 Oct 9 BACKGROUND: Few studies on rheumatoid arthritis (RA) have generated machine learning models to predict biologic disease-modifying antirheumatic drugs (bDMARDs) responses; however, these studies included insufficient analysis on important features. Moreover, machine learning is yet to be used to predict bDMARD responses in ankylosing spondylitis (AS). Thus, in this study, machine learning was used to predict such responses in RA and AS patients. METHODS: Data were retrieved from the Korean College of Rheumatology Biologics therapy (KOBIO) registry. The number of RA and AS patients in the training dataset were 625 and 611, respectively. We prepared independent test datasets that did not participate in any process of generating machine learning models. Baseline clinical characteristics were used as input features. Responders were defined as those who met the ACR 20% improvement response criteria (ACR20) and ASAS 20% improvement response criteria (ASAS20) in RA and AS, respectively, at the first follow-up. Multiple machine learning methods, including random forest (RF-method), were used to generate models to predict bDMARD responses, and we compared them with the logistic regression model. RESULTS: The RF-method model had superior prediction performance to logistic regression model (accuracy: 0.726 [95% confidence interval (CI): 0.725-0.730] vs. 0.689 [0.606-0.717], area under curve (AUC) of the receiver operating characteristic curve (ROC) 0.638 [0.576-0.658] vs. 0.565 [0.493-0.605], F1 score 0.841 [0.837-0.843] vs. 0.803 [0.732-0.828], AUC of the precision-recall curve 0.808 [0.763-0.829] vs. 0.754 [0.714-0.789]) with independent test datasets in patients with RA. However, machine learning and logistic regression exhibited similar prediction performance in AS patients. Furthermore, the patient self-reporting scales, which are patient global assessment of disease activity (PtGA) in RA and Bath Ankylosing Spondylitis Functional Index (BASFI) in AS, were revealed as the most important features in both diseases. CONCLUSIONS: RF-method exhibited superior prediction performance for responses of bDMARDs to a conventional statistical method, i.e., logistic regression, in RA patients. In contrast, despite the comparable size of the dataset, machine learning did not outperform in AS patients. The most important features of both diseases, according to feature importance analysis were patient self-reporting scales.
33450324 MiR-30a-3p ameliorates oxidative stress in rheumatoid arthritis synovial fibroblasts via a 2021 Apr The downregulation of miR-30a-3p has been reported in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS); however, it is poorly understood its possible involvement and the underlying mechanism. The effects of miR-30a-3p overexpression on the proliferation and apoptosis as well as oxidative stress injury were evaluated in rats RA-FLS. The targeting relationship between miR-30a-3p and Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) or cullin3 (cul3) was assessed by luciferase reporter assays. The reduced expression of miR-30a-3p was observed in hydrogen peroxide (H(2)O(2))-treated rat RA-FLS. Functional analysis indicated that the restoration of miR-30a-3p expression reversed H(2)O(2)-induced FLS proliferation and oxidative stress and induced apoptosis. Mechanistic analyses further revealed that Keap1 and cul3 were both downstream targets of miR-30a-3p. Further investigation indicated that miR-30a-3p agomir exerted anti-arthritic effects on adjuvant-induced arthritis (AA) in rats. Targeting Keap1 or cul3 by miR-30a-3p activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to protect FLS against oxidative stress. The miR-30a-3p/Nrf2-Keap1-cul3 pathway axis might be a potential therapy for RA.
34405833 Atopic Dermatitis is a Risk Factor for Rheumatoid Arthritis: A Systematic Review and Meta- 2021 Oct 1 BACKGROUND: It is still unclear whether patients with atopic dermatitis (AD) have an increased risk of developing rheumatoid arthritis (RA). OBJECTIVE: We aimed to investigate the association between AD and risk of RA using systematic review and meta-analysis. METHODS: We searched Medline and EMBASE up to April 2021 using search strategy, including terms for "atopic dermatitis" and "rheumatoid arthritis." Eligible cohort study must compare the incidence of RA between patients with AD and comparators without AD. Eligible case-control study must recruit cases with RA and controls without RA. Then, the study must compare the prevalence of AD between the groups. Point estimates with standard errors from each study were combined using the generic inverse variance method. RESULTS: The meta-analysis found that AD patients had a significantly higher risk of incident RA than individuals without AD with a pooled odds ratio (OR) of 1.30 (95% confidence interval [CI], 1.17-1.44; I2, 48%). Subgroup analysis revealed a significantly higher risk of RA in cohort study subgroup (pooled OR, 1.37; 95% CI, 1.25-1.50; I2, 63%) but not case-control study subgroup (pooled OR, 0.99; 95% CI, 0.77-1.28; I2, 10%). CONCLUSIONS: This study found a significantly higher risk of incident RA among AD patients.
34404269 It Is Like a Puppet Show-Experiences of Rheumatoid Arthritis Among Adult Chinese: A Qualit 2022 Jun Rheumatoid arthritis results in progressive destruction of the joints. However, descriptions of patient's experiences with the disease are limited. This qualitative study aimed to explore patients' personal experiences with rheumatoid arthritis in Taiwan. Face-to-face interviews were conducted with 30 patients from January to May 2019; interview data were analyzed with content analysis. Most participants were female (90%); their mean age was 57 years. Three main categories emerged from analysis of the data: "physical suffering," "limitations of abilities," and "coexisting with the disease." Physical suffering was due to personal lifelong hardships from chronic pain and stiffness. Limitations of abilities occurred from loss of physical function and limited social life, due to participants discomfort with joint deformities and their appearance to others. Participants coexisted with the disease by making changes in their outlook and comparing their lives with others in order to gain a positive perspective.
33913028 Differential Metabolome in Rheumatoid Arthritis: a Brief Perspective. 2021 Apr 28 PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is a chronic autoimmune, inflammatory disease of the synovium that affects the movable joints. It develops due to the infiltration and invasion of the synovial joints by immune cells. Metabolism is anabolic or catabolic chemical reactions occurring in a cell. The biochemical pathways in synovial and immune cells are altered affecting the downstream metabolite formation. Changes in the metabolite levels alter signaling cascades which further intensify the disease. Despite current knowledge of metabolomics, there remain certain features that need to be elucidated to correlate the differential metabolite levels with RA. RECENT FINDINGS: Metabolite profiling can be used to find altered patterns of metabolites in RA. Glucose, lipid, amino acid, and estrogen metabolism are the key pathways that are altered and contribute to the aggravation of RA. The altered metabolic pathways involved in different cells in RA results in complex interactions between metabolites and biomacromolecules; thus, it generates autoantigens. Moreover, understanding the correlation between differential metabolites and disease severity might help reveal potential new biomarkers and therapeutic targets for RA pathogenesis. So, considering the multi-faceted role of altered metabolites in the pathogenesis of RA, metabolic pathways of different cells are needed to be studied for a better understanding of their functions in the disease and thus, improving the present therapeutic strategies.
34058807 [Expert consensus on clinical detection of rheumatoid arthritis related autoantibodies]. 2021 Jun 1 Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Early diagnosis and standard treatment are the keys to control the disease and improve the prognosis. A variety of autoantibodies such as rheumatoid factor and anti-citrullinated peptide/protein antibodies can be detected in serum of patients with rheumatoid arthritis, which are important for early diagnosis and differential diagnosis of RA, judgment of disease severity and prognosis evaluation. The standardization of autoantibody detection related to rheumatoid arthritis is very important for its clinical application. Under the organization of the Committee of the Autoantibodies Detection of Rheumatology and Immunology Physicians Committee of Chinese Medical Doctor Association, expert consensus on clinical application of rheumatoid arthritis related autoantibodies detection were established by a joint group of Chinese multi-disciplinary experts. The consensus aims to standardize the detection of RA associated autoantibodies, and to provide a reference for clinicians and laboratory technicians to use and interpret rheumatoid arthritis-related autoantibodies in daily practice.
33191869 Arthroscopic triple arthrodesis for the patient with rheumatoid arthritis; a case report. 2021 Jan We treated a 60 - year - old man with pes planovalgus due to rheumatoid arthritis. He had been suffering from left foot pain with swelling. Despite drug therapy, his foot pain and deformity had got worsen. Taking into consideration his skin and bone quality, arthroscopic triple arthrodesis was performed. To access the subtalar joint, 2 portals were applied at the sinus tarsi, and decortication was performed. For calcaneocuboid joint, 1.5 cm portal was applied along with joint line at calcaneocuboid joint. Calcaneocuboid joint was fully decorticated, then, 1.5 cm portal was applied at the joint line of talonavicular joint in parallel. Synovectomy and decortication under arthroscopy were performed. Once each joint was sufficiently prepared, it was fixed using screws via a percutaneous stab incision with an autologous bone graft from the iliac crest to the calcaneocuboid and talonavicular joint. At 12 weeks postoperatively, bone union was confirmed. The Japan Society for Surgery of the Foot (JSSF) RA foot and ankle scale had improved from the postoperative value of 38 points to a postoperative score of 86 points at one year. Plain radiographs showed that good alignment of the patient's hindfoot was maintained. We found that arthroscopic approach was able to achieve satisfactory outcome and minimise soft tissue trauma in a compromised patient.
33746199 Low-Concentration (0.66%) Povidone Iodine Treatment of a Corneal Ulcer in a Rheumatoid Art 2021 Mar 22 BACKGROUND Peripheral ulcerative keratitis is one of the ocular complications associated with chronic inflammatory immune-mediated diseases, such as rheumatoid arthritis, in which inflammatory reactions and infections can be recurrent. Suspected infections are treated with topical antibiotics that, in some cases, may promote selection of resistant microbes. Povidone iodine is known for its rapid broad-spectrum activity against all kinds of microbes and biofilms, lack of microbial resistance, ability to counteract excessive inflammation, and efficacy in wound healing, along with an optimum safety and tolerability profile. The purpose of this case report is to show the resolution of a peripheral ulcerative keratitis case by means of treatment with 0.66% povidone iodine. CASE REPORT An 89-year-old woman with rheumatoid arthritis, 1 eye, and a superior descemetic corneal ulcer was treated with amniotic membrane, topical antibiotics, and antiviral drugs without any control of clinical signs and symptoms. Therefore, all anti-infective treatments were replaced with 0.66% povidone iodine (3 times/day) given alone for 5 weeks and then associated with serum eyedrops. When a clear regression of the ulcer was observed, the patient was maintained with serum eyedrops only. CONCLUSIONS Unusual treatment with povidone iodine 0.66% (used for the first time in an autoimmune patient), alone and in association with serum eyedrops, probably contributed to alleviate the signs and symptoms of a case of peripheral ulcerative keratitis not responding to conventional treatments. Although its regular use warrants further investigation, povidone iodine seems a useful therapeutic tool for the treatment of corneal ulcers associated with chronic immune-mediated inflammatory diseases.
34796986 Ratio of serum amyloid A to C-reactive protein is constant in the same patients but differ 2022 Feb C-reactive protein (CRP) is commonly monitored to track the activity of inflammation and has become the gold standard in the management of all inflammatory diseases. Indeed, serum amyloid A (SAA) have seemed to correlate moderately with CRP, but the discrepancy of CRP and SAA levels has often been reported, especially in rheumatoid arthritis. Then, we examined CRP reflects a real magnitude of inflammation in patients with rheumatic and infectious inflammatory diseases. A total of 414 patients with infectious and non-infectious inflammatory diseases were enrolled. At initial visit, each patient underwent a clinical assessment and had also laboratory tests such as SAA and CRP. In each patient, we carried out a longitudinal analysis of CRP and SAA levels. We determined the inter-individual correlation between SAA and CRP and also clarified intra-individual changes of SAA/CRP ratio. SAA and CRP levels changed approximately linearly over time within individuals irrespective of rheumatic and infectious inflammatory diseases. However, SAA/CRP ratios differed dramatically between patients (from 0.117 to 50.8, median 5.71). In patients with high SAA/CRP ratio (>8.44), SAA is a better predictor of inflammation than CRP. In contrast, CRP is a better predictor in patients with low ratio (<3.52). Our results suggest that the SAA/CRP ratio differed greatly between individuals but was constant in intra-individuals. Low CRP levels could be accompanied by SAA levels predicting any degree of inflammation, implying that CRP is not reflecting a real magnitude of inflammation. To evaluate the real magnitude of inflammation, to access the SAA/CRP ratio in advance is essential.
33635223 Difficult-to-treat rheumatoid arthritis with respect to responsiveness to biologic/targete 2022 Jan OBJECTIVES: Difficult-to-treat rheumatoid arthritis (dt-RA) is an emerging concept defined as persistency of signs and/or symptoms despite prior treatment. However, whether this refractoriness affects effectiveness and tolerance to next treatment is not fully understood. This study aimed to find cut-off values for a definition of dt-RA with respect to responsiveness to newly used biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: A retrospective cohort study was conducted using the FIRST registry. An inadequate response to current b/tsDMARDs was defined as clinical disease activity index >10 at week 22 or termination of treatment within 22 weeks due to insufficient efficacy. Cut-off values were defined according to the number of past failures to DMARDs and current dose of glucocorticoid. Responsiveness to newly used b/tsDMARDs were compared with respect to above versus below cut-off values. RESULTS: Failures to ≥2 conventional synthetic DMARDs (csDMARDs) and ≥4 b/tsDMARDs as well as ≥3mg/day of glucocorticoid were independent cut-off values associated with poor responsiveness to newly used b/tsDMARD treatment. Concomitant use of glucocorticoid was significantly correlated with an increased hazard of infection. Failures to ≥2 csDMARDs was associated with less improvement in inflammatory symptoms, while that to ≥4 b/tsDMARDs was associated with less improvement in health assessment questionnaire and global health as well. CONCLUSIONS: We propose cut-off values of ≥2 failures to csDMARDs and/or ≥4 b/tsDMARDs as a definition of dt-RA with respect to responsiveness to use of b/tsDMARDs.
33584647 Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Th 2020 Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H(+)-activated cation channel family. Emerging evidence has suggested that ASIC1a plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Specifically, ASIC1a could promote inflammation, synovial hyperplasia, articular cartilage, and bone destruction; these lead to the progression of RA, a chronic autoimmune disease characterized by chronic synovial inflammation and extra-articular lesions. In this review, we provided a brief overview of the molecular properties of ASIC1a, including the basic biological characteristics, tissue and cell distribution, channel blocker, and factors influencing the expression and function, and focused on the potential therapeutic targets of ASIC1a in RA and possible mechanisms of blocking ASIC1a to improve RA symptoms, such as regulation of apoptosis, autophagy, pyroptosis, and necroptosis of articular cartilage, and synovial inflammation and invasion of fibroblast-like cells in synovial tissue.
34269927 Doppler ultrasound impacts response to intravenous tocilizumab in rheumatoid arthritis pat 2021 Dec OBJECTIVE: Within rheumatoid arthritis (RA) patients treated with intravenous tocilizumab (IV-TCZ), it is unclear if power Doppler ultrasonography (PDUS) can predict future clinical response. This study sought to determine if baseline PDUS or its early changes can predict 12-week and 24-week disease activity outcomes, and quantify the need for dose escalation (4 to 8 mg/kg). METHODS: Fifty-four RA patients starting IV-TCZ were evaluated at baseline, 4, 6, 12, 16, and 24 weeks using 34-joint PDUS (US34-PDUS), clinical disease activity index (CDAI), 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR), ACR 20/50/70, health assessment questionnaire-disability index (HAQ-DI), and PDUS 20/50/70, a novel measure. Logistic regression models evaluated the predictive utility of US34-PDUS of DAS28-ESR response after adjusting for covariates. RESULTS: Ninety-four percent of patients required dose escalation to 8 mg/kg. US34-PDUS, CDAI, and DAS28-ESR improved significantly over 24 weeks (p < 0.001). Baseline PDUS and 12-week PDUS change correlated with CDAI at 24 weeks (p < 0.05). Logistic regression demonstrated baseline US34-PDUS was independently associated with DAS28-ESR ≥ 1.2 response, even after adjusting for baseline DAS28-ESR (p = 0.03). CDAI, DAS28-ESR, and their components increased across PDUS 20/50/70 categories; however, HAQ-DI did not. CONCLUSION: RA patients treated with IV-TCZ for 24 weeks demonstrated significant improvement, and baseline/early changes in PDUS were predictive of later clinical response. The PDUS 20/50/70 measure is a novel metric of response. This study suggests that IV-TCZ 4 mg/kg may not be sufficient to attain low RA disease activity at 12 weeks, in RA patients with moderate to severe disease (DAS28 ≥ 4.4 and US34-PDUS ≥ 10). TRIAL REGISTRATION: ClinicalTrials.gov NCT01717859 Key Points • Over 90% of RA patients with baseline DAS28-ESR ≥ 4.4 and PDUS34 ≥ 10 required intravenous tocilizumab dose escalation from 4 to 8 mg/kg at 12 weeks. • Reduction in power Doppler ultrasonography (US34-PDUS) scores correlate with DAS28-ESR and CDAI over 24 weeks in rheumatoid arthritis patients with moderate to severe disease activity. • Baseline US34-PDUS predicts future improvements in clinical disease activity outcomes, independent of baseline DAS28-ESR. • Clinical response measures, DAS28-ESR and CDAI, improved across US34-PDUS 20/50/70 categories, while patient-reported outcomes did not.
33868244 Function and Role of Regulatory T Cells in Rheumatoid Arthritis. 2021 Rheumatoid arthritis (RA) is a systemic and heterogeneous autoimmune disease with symmetrical polyarthritis as its critical clinical manifestation. The basic cause of autoimmune diseases is the loss of tolerance to self or harmless antigens. The loss or functional deficiency of key immune cells, regulatory T (Treg) cells, has been confirmed in human autoimmune diseases. The pathogenesis of RA is complex, and the dysfunction of Tregs is one of the proposed mechanisms underlying the breakdown of self-tolerance leading to the progression of RA. Treg cells are a vital component of peripheral immune tolerance, and the transcription factor Foxp3 plays a major immunosuppressive role. Clinical treatment for RA mainly utilizes drugs to alleviate the progression of disease and relieve disease activity, and the ideal treatment strategy should be to re-induce self-tolerance before obvious tissue injury. Treg cells are one of the ideal options. This review will introduce the classification, mechanism of action, and characteristics of Treg cells in RA, which provides insights into clinical RA treatment.
32896242 The ovarian reserve as measured by the anti-Müllerian hormone is not diminished in patien 2021 Mar OBJECTIVES: Rheumatoid arthritis (RA) is the most prevalent chronic inflammatory arthritis, affecting 0.5-1% worldwide population and predominates in females. Altered fertility has been reported due to a decrease in ovarian reserve secondary to sustained inflammation. The anti-Müllerian Hormone (AMH) is currently the most reliable biomarker of ovarian reserve. However, few and contradictory studies have been reported to analyse the relationship between fertility in RA female patients and AMH. The aim of present study is to determine the AMH serum concentrations in a long-standing RA patient group and control group. We also sought to determine the correlation between AMH serum levels and disease activity measured by different parameters and the effect of biological DMARDs. METHODS: Serum AMH levels were measured in 60 women with long-standing RA aged 20-50 y.o. and compared to 59 healthy women. AMH was assessed by an electrochemiluminescence immunoassay method (ECLIA, Roche Diagnostics) and a large data set of clinical and molecular data was annotated. Demographic parameters, RA disease activity measured by DAS28 score and inflammatory biomarkers such as ESR, CRP, lymphocyte CD4+, CD8+, NK cells, IL-10 and IL-6 were determined. A comprehensive gynaecological self-administered questionnaire was given. Serum AMH levels were age-correlated. Differences between groups were calculated using Student's t-test or Mann-Whitney U-test for continuous variables and Fisher's exact test for categorical variables. Multivariate analysis was conducted by the partial correlation coefficient. Linear regression analysis was performed to study the effect of different variables on proportional AMH change. p-values <0.005 were considered significant. RESULTS: The median age was similar in AR and control groups (37.4±6.23 vs. 37.3±6.27 p=0.937). Mean disease duration was 8.37±5.36 years. The number of previous treatments was <3 in 71.7% of patients and ≥3 in 28.3%. Disease activity measured by DAS28 was 2.89± 1.54. The age-adjusted mean serum concentration of AMH was 1.27 ng/ml [IQR 0.42; 2.24] in RA patients and 1.31 ng/ml [IQR 0.46; 3.09] in controls (p=0.608). Neither disease activity (p=0.862), nor current or previous bDMARDs treatments (p=0.871) were associated with AMH levels. However, a negative linear correlation was observed between AMH and IL-10 levels (p=0.033). CONCLUSIONS: Our study shows that ovarian reserve determined by AMH serum levels is not reduced in rheumatoid arthritis patients compared with healthy controls. In our series, AMH levels were not affected by disease activity, however, a significant correlation was observed between AMH and IL-10 levels. These results support the role of cytokines profile in the female reproductive system and will focus further investigations in this critical area, mainly once biological DMARDs have been recommended in RA pregnant patients.