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ID PMID Title PublicationDate abstract
34519965 Differentiating Psoriatic Arthritis from Osteoarthritis and Rheumatoid Arthritis: A Narrat 2021 Dec Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple organ systems and is characterized by skin and joint manifestations. PsA is frequently undiagnosed and/or misdiagnosed, especially because of the similarities in clinical presentation shared with other arthritic diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). An accurate and timely diagnosis of PsA is crucial to prevent delays in optimal treatment, which can lead to irreversible joint damage and increased functional disability. Patients are usually seen by a number of different healthcare providers on their path to a diagnosis of PsA, including advanced practice providers (APPs). This review provides a comprehensive overview of the characteristic features that can be used to facilitate the differentiation of PsA from RA and OA. Detailed information on clinical manifestations, biomarkers, radiologic features, and therapeutic recommendations for PsA included here can be applied in routine clinical settings to provide APPs with the confidence and knowledge to recognize and refer patients more accurately to rheumatologists for management of patients with PsA.
34124603 The relationship between rheumatoid arthritis and diabetes mellitus: a systematic review a 2021 Jun OBJECTIVE: This systematic review/meta-analysis was conducted to investigate the relationship between rheumatoid arthritis and the incidence of diabetes mellitus. METHODS: A comprehensive search was conducted up to 10 March 2020 in Medline (via Ovid), Embase (via Ovid) and Web of Science core collection to identify cohort studies comparing the risk of diabetes mellitus incidence in people with rheumatoid arthritis with the general population. The I2 statistic was used to test heterogeneity. Pooled relative risks were calculated using random-effects models. Publication bias was assessed using Egger's test and Begg's test. RESULTS: The initial search provided 3669 articles. Of those, five journal articles/two conference abstracts comprising 1 629 854 participants were included in this study. The funnel plot showed potential publication bias, proven by Egger's test (-3.15, P < 0.01), but not Begg's test (-0.05, P = 1.00). Heterogeneity was observed in I2 test (I2 = 96%, P < 0.01). We found that rheumatoid arthritis was associated with a higher risk of diabetes mellitus incidence (pooled relative risk, 1.23; 95% confidence interval, 1.07-1.40). Exploration of potential sources of heterogeneity found significant heterogeneity in different countries/regions (P = 0.002), but heterogeneity was NS in different study designs (P = 0.30). Sensitivity analyses confirmed that the association between rheumatoid arthritis and diabetes mellitus incidence was robust. CONCLUSION: Rheumatoid arthritis is associated with an increased risk of diabetes mellitus incidence. This finding supports the notion that inflammatory pathways are involved in the pathogenesis of diabetes. More intensive interventions targeting diabetes risk factors should be considered in people with rheumatoid arthritis.
34707960 Enteroviral Meningoencephalitis as a Complication of Rituximab Therapy for Rheumatoid Arth 2021 Sep Enteroviral meningoencephalitis is a rare complication of rituximab therapy that has been described in the treatment of hematologic malignancies. We report the first case of enteroviral meningoencephalitis in a patient receiving rituximab for the treatment of rheumatoid arthritis. A 37-year-old female treated with rituximab for severe rheumatoid arthritis presented with fever, headache, confusion, and tremor. Magnetic resonance imaging (MRI) of the brain was unrevealing. Cerebrospinal fluid showed a lymphocytic pleocytosis and multiplex polymerase chain reaction (PCR) was positive for enterovirus. She was treated with intravenous immunoglobulin (IVIG) for five days and had significant improvement in symptoms. Rituximab is an anti-CD20 monoclonal antibody that induces B-cell depletion and possible hypogammaglobulinemia, putting patients at increased risk for viral infections. We present this case to highlight that patients on rituximab, regardless of the indication for use, are susceptible to severe complications of otherwise typically self-limited viral infections. Furthermore, we describe the potential use of IVIG in treating these patients.
33708221 Cartilage Oligomeric Matrix Protein Induced Arthritis-A New Model for Rheumatoid Arthritis 2021 The most commonly used strains in experimental research, including genetically modified strains, are C57BL/6 mice. However, so far, no reliable model for rheumatoid arthritis is available, mainly due to the restriction by the MHC class II haplotype H-2(b). Collagen-induced arthritis (CIA) is the most widely used animal model of rheumatoid arthritis, but C57BL/6 strain is resistant to CIA because there is no collagen II peptide associated with H-2(b). To establish a rheumatoid arthritis model in C57BL/6 mice, we immunized C57BL/6NJ (B6N) mice with human cartilage oligomeric matrix protein (COMP), which induced severe arthritis with high incidence, accompanied by a strong auto-antibody response. Native COMP was required, as denatured COMP lost its ability to induce arthritis in B6N mice. An immunodominant COMP peptide was identified as the key T cell epitope, with a perfect fit into the A(b) class II peptide binding pocket. A critical amino acid in this peptide was found to be phenylalanine at position 95. Recombinant COMP mutated at position 95 (COMP_F95S) lost its ability to induce arthritis or a strong immune response in the B6N mice. In conclusion, A new model for RA has been established using C57BL/6 mice through immunization with COMP, which is dependent on a COMP specific peptide binding A(b), thus in similarity with CIA in A(q) expressing strains.
34926155 Anti-cyclic citrullinated peptide antibody (ACPA) and Rheumatoid arthritis: Clinical relev 2022 Jan Rheumatoid Arthritis (RA) is the most common auto-immune, chronic inflammatory joint disease. Predominantly a musculoskeletal condition with a wide spectrum of skeletal and extra-skeletal manifestations, RA has a significant footfall in orthopaedic clinical practice worldwide. RA is essentially a clinical diagnosis; however, laboratory and radiographic investigations can provide complementary diagnostic and prognostic information about the disease. Early diagnosis and initiation of appropriate management are crucial since RA patients can develop chronic, erosive arthritis if left untreated or if treatment is delayed. Rheumatoid Factor (RF) antibody test is routinely employed for diagnostic purposes in patients with suspected RA. However, RF is present only in 70%-80% of patients with RA and can be non-specific. Therefore, Anti-cyclic citrullinated peptide antibody (ACPA), a novel immunological marker for RA is increasingly being utilised to provide higher specificity and a better prognostic indicator in RA patients. We describe the immunological basis of ACPA test and highlight its current applications in the diagnosis, prognosis and monitoring of RA in clinical practice.
32648101 Neurological manifestations of adult-onset Still's disease-case-based review. 2021 Jan Adult-onset Still's disease (AOSD) is a rare inflammatory disorder in which pathophysiology is yet to be fully understood. We report the case of a 66-year-old male that presents with fever, arthralgia, and laboratory abnormalities suggestive of a systemic inflammatory disease. During a diagnostic workout, the patient developed neurological symptoms, namely a sudden confounding syndrome and hearing loss that improved with corticosteroid therapy. After exclusion of malignancy, infection-namely nervous system infection-and other rheumatic diseases, AOSD diagnosis was made using the Yamaguchi criteria. In some rare cases, neurological symptoms are present and the diagnosis may become even more challenging if the clinicians are not aware of these rare manifestations of AOSD. Therefore, the authors present the case of a patient with neurological manifestations of AOSD.
33660820 The gelsolin level in patients with primary Sjogren's syndrome. 2021 Feb OBJECTIVE: Gelsolin (GSN) is a multifunctional protein that can regulate cell proliferation, apoptosis, inflammation and infection. GSN has been reported to be involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and many other diseases. The role of GSN in primary Sjogren's syndrome (pSS) remains still unclear. The aim of this study is to investigate the changes of GSN level in serum and whole blood cells of pSS patients and evaluate the relationship between GSN and fatigue or other clinical indicators. PATIENTS AND METHODS: The cross-sectional study included 47 pSS patients (1 male and 46 females, average age: 52.83±12.63 years) and 51 healthy controls (all females, average age: 50.61±9.86 years). The patients were collected from the Second Affiliated Hospital of Harbin Medical University, China, without the age and sex differences. The levels of GSN in serum of pSS patients and the healthy controls were measured by Western blotting. The sequencing gene expression omnibus (GEO) data from National Center for Biotechnology Information (NCBI) about GSN levels in the whole blood cells of pSS patients and the healthy controls were analyzed by R language. RESULTS: Compared with healthy controls, the level of GSN was significantly decreased in the serum of pSS patients (98.89 ± 28.94 vs. 131.6 ± 37.1 µg/ml, p<0.001). The expression of GSN in the whole blood cells of pSS patients was significantly lower than that in the healthy controls (6.4 ± 0.19 vs. 6.6 ± 0.17, p<0.01). Compared to non-fatigued pSS patients, the level of GSN was down-regulated in serum (85.69 ± 27.08 vs. 111.52 ± 24.71 µg/ml, p<0.01) and whole blood cells (6.43 ± 0.18 vs. 6.58 ± 0.21, p<0.001) in fatigue pSS patients. However, there was no significant correlation between the level of GSN and EULAR Sjogrens syndrome disease activity index (ESSDAI) in pSS patients (p=0.73). CONCLUSIONS: GSN is decreased in serum and whole blood cells of pSS patients, and it is much lower in fatigue patients than that in non-fatigue patients. The correlation between the level of GSN and ESSDAI was not significant in pSS patients.
34736402 The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes. 2021 Nov 4 Auto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.
34059137 Potential clinical biomarkers in rheumatoid arthritis with an omic approach. 2021 May 31 OBJECTIVE: To aid in the selection of the most suitable therapeutic option in patients with diagnosis of rheumatoid arthritis according to the phase of disease, through the review of articles that identify omics biological markers. METHODS: A systematic review in PubMed/Medline databases was performed. We searched articles from August 2014 to September 2019, in English and Spanish, filtered by title and full text; and using the terms "Biomarkers" AND "Rheumatoid arthritis". RESULTS: This article supplies an exhaustive review from research of objective measurement, omics biomarkers and how disease activity appraise decrease unpredictability in treatment determinations, and finally, economic, and clinical outcomes of treatment options by biomarkers' potential influence. A total of 122 articles were included. Only 92 met the established criteria for review purposes and 17 relevant references about the topic were included as well. Therefore, it was possible to identify 196 potential clinical biomarkers: 22 non-omics, 20 epigenomics, 33 genomics, 21 transcriptomics, 78 proteomics, 4 glycomics, 1 lipidomics and 17 metabolomics. CONCLUSION: A biomarker is a measurable indicator of some, biochemical, physiological, or morphological condition; evaluable at a molecular, biochemical, or cellular level. Biomarkers work as indicators of physiological or pathological processes, or as a result of a therapeutic management. In the last five years, new biomarkers have been identified, especially the omics, which are those that proceed from the investigation of genes (genomics), metabolites (metabolomics), and proteins (proteomics). These biomarkers contribute to the physician choosing the best therapeutic option in patients with rheumatoid arthritis.
34784872 Understanding the Role and Uses of Alternative Therapies for Management of Rheumatoid Arth 2021 Nov 15 With growing popularity of complementary and alternative medicine (CAM) among the individuals with chronic pain and muscular problems, a number of patients with rheumatoid arthritis (RA) show their interest in CAM interventions for disease improvement. Various reports published on CAM are based on animal model of RA however there is often lack of high quality clinical investigations for explaining the success stories of CAM therapies in patients with RA. CAMs having potential to be used for therapy in patients with RA have been identified, however lack of awareness and scepticism of their efficacy has made the patients reluctant to choose these drug less therapies. In this review, we have summarized the existing evidences which suggest promising efficacy of different alternative therapies in managing RA and providing both physical and mental well being to RA patients.
35003971 Mesenteric Panniculitis: A Rare Condition in a Patient With Rheumatoid Arthritis. 2021 Dec Rheumatoid arthritis is a relatively common chronic inflammatory disorder affecting the synovial joints. Extra-articular manifestations of rheumatoid arthritis are not uncommon and include a wide range of cardiovascular, pulmonary, and neurological complications. Gastrointestinal involvement in rheumatoid arthritis is rare, but it can be impactful on the quality of life of patients. We present the case of a 45-year-old woman, with rheumatoid arthritis on methotrexate, who presented with a one-week history of abdominal pain. The patient visited the outpatient clinic earlier and was diagnosed with indigestion and was offered symptomatic treatment which failed to provide any improvement. Abdominal examination revealed a distended abdomen with generalized tenderness and rebound. However, the abdomen was soft with no palpable masses. Initial laboratory examination, including inflammatory parameters, was normal. The patient underwent a computed tomography scan of the abdomen with intravenous contrast which demonstrated inhomogeneous hyperdense mesenteric fat giving a mass-like lesion with a displacement of adjacent bowel loops. Such findings conferred the diagnosis of mesenteric panniculitis. The patient was started on corticosteroid therapy with oral prednisolone 40 mg daily with close follow-up. She developed gradual improvement in her condition and the pain resolved completely after six days. The patient was re-evaluated after six months from discharge and she had no recurrence. The case highlighted a rare association of mesenteric panniculitis and rheumatoid arthritis. Physicians should keep this mesenteric panniculitis in mind when they encounter patients with the autoimmune disorders who presented with abdominal symptoms.
34584791 Predictors of Quality of Life in Patients With Rheumatoid Arthritis in Pakistan: A Cross-S 2021 Aug Introduction Rheumatoid arthritis (RA) is a chronic, progressive inflammatory illness that primarily affects peripheral joints and belongs to systemic connective tissue diseases. Rheumatoid arthritis can cause varied and significant impacts on patients' health, including mental and physical wellbeing. The aim of this study is to analyze the factors affecting the quality of life of rheumatoid arthritis patients. Methodology A cross-sectional study was conducted in the outpatient orthopedics department of Indus Hospital and Health Network. The survey questionnaire was used to collect data from participants. The study's 36-item short-form survey (SF-36) questionnaire was used to assess the quality of life (QoL) among RA patients. Linear regression was used to assess the factors associated with the mental and physical components of QoL. Results A total of 154 patients were interviewed in this study. The mean age of participants was 48.96 (±51.35). Factors that contributed to the physical component of QoL included severity of disease, income, age, comorbidity, and anxiety while factors affecting the mental component of QoL included quality of sleep, anxiety, education, comorbidity, and disease severity. Conclusion Healthcare professionals need to work closely with patients to increase their capabilities of being more independent and controlling all the factors that can affect their QoL.
35444819 New Inflammatory Marker Associated with Disease Activity in Rheumatoid Arthritis: The Syst 2021 Oct OBJECTIVE: This study aimed to discover a new index for disease activity by reviewing the relationship between the Systemic Immune-Inflammation Index and Systemic Inflammation Response Index in rheumatoid arthritis. METHOD: A total of 109 patients with rheumatoid arthritis and 31 healthy controls were involved in the study. Based on disease activity score (DAS-28) calculated by the erythrocyte sedimentation rate, rheumatoid arthritis patients were divided into two groups: Group 1 comprised patients in remission (DAS-28<2.6); Group 2 was the active patient group (DAS-28>2.6). The Systemic Immune Inflammation Index and the Systemic Inflammation Response Index compared between the groups. RESULTS: The Systemic Immune-Inflammation Index is 666.415±33.00 in the patient group and 596.71±57.64 in the control group, and the difference between the groups is statistically significant (p=0.002). The Systemic Immune-Inflammation Index was 574.69±34.72 in group 1 and 702.25±39.56 in group 2. There was a significant statistical difference between the active and remission patients (p=0.030). The Systemic Inflammation Response Index was not statistically significant between the groups. Different cut-off points were compared to detect the optimal cut-off value for SII. Based on the ROC curve analysis, SII cut-off point of 574.20 showed 56.3% sensitivity and 45.5% specificity and with the Area Under Curve (AUC) 95% was the optimal cut-off point for active RA. CONCLUSION: This is the first study to review the Systemic Immune-Inflammation Index in rheumatoid arthritis. The obtained conclusion verified that the Systemic Immune-Inflammation Index could be used as a new tool, showing disease activity.
34322656 Disease impact of rheumatoid arthritis in patients not treated with advanced therapies; 2021 OBJECTIVE: The aim was to reveal the everyday impact of living with RA in people not treated with advanced therapies (i.e. biologic or targeted synthetic DMARDs). METHODS: People with RA, with disease duration >2 years, not currently treated with advanced therapies, completed an online survey promoted by the National Rheumatoid Arthritis Society. Items covered demographics, current treatment, RA flare frequency, the Rheumatoid Arthritis Impact of Disease (RAID) tool and questions reflecting work status and ability. Descriptive and multivariable regression analyses were performed. RESULTS: There were 612 responses from patients having a mean age of 59 years, 88% female, 37.7% with disease duration 2-5 years and 27.9% with disease duration 5-10 years. In the last year, 90% reported an RA flare, with more than six flares in 23%. A RAID patient acceptable state was recorded in 12.4%. Each of the seven domains was scored in the high range by >50% respondents; 74.3% scored sleep problems and 72% fatigue in the high range. A need to change working hours was reported by 70%. Multivariable analyses revealed that increasing difficulties with daily physical activities, reduced emotional and physical well-being in the past week were all significantly associated with pain, number of flares and ability to cope (P < 0.005). The RAID score was significantly predictive of the number of flares. CONCLUSION: Patients not currently treated with advanced therapies experience profound difficulties in everyday living with RA, across a broad range of measures. We advocate that patient-reported measures be used to facilitate holistic care, addressing inflammation and other consequences of RA on everyday life.
34447584 Pancreatic Rheumatoid Granulomas: A Case Report of a Rare Complication of Rheumatoid Arthr 2021 Jul Cutaneous granulomas presenting as skin nodules are the most common extra-articular manifestations of rheumatoid arthritis (RA). Granulomas are defined as a form of chronic inflammatory response characterized by aggregation of activated histiocytes. Visceral granulomas are a rare complication of long-standing RA and have been described twice in the literature. We report a case of a 55-year-old woman with a 15-year history of RA. The patient presented with epigastric pain and weight loss. Imaging studies showed a large soft tissue mass in the head of the pancreas, which was suspected to be malignant. A Whipple procedure was performed, and histological examination revealed multiple non-caseating granulomas with central liquefaction and neutrophilic infiltrate. Ziehl-Neelsen stain for acid-fast bacilli and tuberculosis polymerase chain reaction were negative. The patients' granulomas were diagnosed as rheumatoid granulomas. Five years after diagnosis, the patient is doing well and has no complications.
34777472 MicroRNA Variants and HLA-miRNA Interactions are Novel Rheumatoid Arthritis Susceptibility 2021 Genome-wide association studies have identified >100 genetic risk factors for rheumatoid arthritis. However, the reported genetic variants could only explain less than 40% heritability of rheumatoid arthritis. The majority of the heritability is still missing and needs to be identified with more studies with different approaches and populations. In order to identify novel function SNPs to explain missing heritability and reveal novel mechanism pathogenesis of rheumatoid arthritis, 4 HLA SNPs (HLA-DRB1, HLA-DRB9, HLA-DQB1, and TNFAIP3) and 225 common SNPs located in miRNA, which might influence the miRNA target binding or pre-miRNA stability, were genotyped in 1,607 rheumatoid arthritis and 1,580 matched normal individuals. We identified 2 novel SNPs as significantly associated with rheumatoid arthritis including rs1414273 (miR-548ac, OR = 0.84, p = 8.26 × 10(-4)) and rs2620381 (miR-627, OR = 0.77, p = 2.55 × 10(-3)). We also identified that rs5997893 (miR-3928) showed significant epistasis effect with rs4947332 (HLA-DRB1, OR = 4.23, p = 0.04) and rs2967897 (miR-5695) with rs7752903 (TNFAIP3, OR = 4.43, p = 0.03). In addition, we found that individuals who carried 8 risk alleles showed 15.38 (95%CI: 4.69-50.49, p < 1.0 × 10(-6)) times more risk of being affected by RA. Finally, we demonstrated that the targets of the significant miRNAs showed enrichment in immune related genes (p = 2.0 × 10(-5)) and FDA approved drug target genes (p = 0.014). Overall, 6 novel miRNA SNPs including rs1414273 (miR-548ac, p = 8.26 × 10(-4)), rs2620381 (miR-627, p = 2.55 × 10(-3)), rs4285314 (miR-3135b, p = 1.10 × 10(-13)), rs28477407 (miR-4308, p = 3.44 × 10(-5)), rs5997893 (miR-3928, p = 5.9 × 10(-3)) and rs45596840 (miR-4482, p = 6.6 × 10(-3)) were confirmed to be significantly associated with RA in a Chinese population. Our study suggests that miRNAs might be interesting targets to accelerate understanding of the pathogenesis and drug development for rheumatoid arthritis.
34754908 Felty's syndrome - a rare case of febrile neutropenia. 2019 Felty's syndrome (rheumatoid arthritis with neutropenia and splenomegaly) is a rare condition with poor long-term prognosis, mainly as a result of severe infection risk. An effective treatment strategy has not been developed so far and current treatment options are based upon case reports, small series and clinical experience since no randomized clinical trials are available. The authors describe the case of a 53-year-old female patient with a 14-year history of rheumatoid arthritis presenting with fever, neutropenia and splenomegaly. Broad-spectrum antibiotics and granulocyte colony-stimulating factor were administered with good clinical outcome and low dose methotrexate for disease control was successfully initiated after discharge. We would like to highlight the importance of being aware of this syndrome in the differential diagnosis of long term rheumatoid arthritis patients presenting with febrile neutropenia.
34527489 The Co-existence of Rheumatoid Arthritis and Granulomatosis With Polyangiitis: Two Cases a 2021 Aug Granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA) have shared features including vasculitis, ocular inflammation, interstitial lung disease, and arthritis but existing evidence indicates they are distinct conditions. Interestingly, the co-existence of GPA and RA has been described in the literature. Herein, we report two cases of GPA developing in patients with underlying RA and examine the relationship between the two conditions. Two cases of GPA that developed in patients with preexisting RA are described in detail. Additionally, PubMed was searched for articles in English showing an association of RA and GPA using keywords "rheumatoid arthritis, and vasculitis, and Wegener's, and ANCA, and granulomatosis polyangiitis." In addition to our two cases of RA and GPA overlap, 14 reports were identified in PubMed library from 1970 to 2020. Most of the cases were females (14/16, 88%), and had RA as the initial diagnosis (15/16, 94%). The mean age of RA diagnosis was 45.5 years, the mean age of GPA diagnosis was 52 years and the mean interval between both diagnoses was 101 months. Cyclophosphamide and steroid therapy were used in most of the cases. There are numerous reports of GPA and RA overlap in the literature. GPA should be considered in the differential diagnosis when vasculitis develops in patients with RA.
34352094 The susceptibility of attaining and maintaining DMARD-free remission in different (rheumat 2021 Aug 5 OBJECTIVES: To compare (sustained) DMARD-free remission rates((S)DFR), defined as respectively ≥6 months and >1 year, after 2 and 5 years between three clinical arthritis phenotypes; undifferentiated arthritis(UA), autoantibody-negative(RA-) and positive rheumatoid arthritis(RA+). METHODS: All UA(n = 130), RA-(n = 176) and RA + (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. (S)DFR comparisons between phenotypes after 2 and 5 years were performed with Logistic regression. Medication use and early and late flares(DAS ≥ 2.4), respectively defined as < 12 and >12 months after reaching DFR, were also compared. Cox proportional hazard models were used to evaluate potential predictors for (S)DFR. RESULTS: Within 2 and 5 years less DFR was seen in RA + (17.2-25.7%), followed by RA-(28.4-42.1%) and UA patients(43.1-58.5%). This also applied for SDFR within 2 and 5 years (respectively 7.6% and 21.4%; 20.5% and 38.1%; and 35.4% and 55.4%). A flare during tapering was seen in 22.7% of patients. Of the patients in DFR 7.5% had an early flare and 3.4% a late flare. Also more treatment intensifications occurred in RA+ compared with RA- and UA. We found that higher baseline DAS, ACPA positivity, BMI and smoking were negatively associated with (S)DFR, while clinical phenotype(reference RA+), short symptom duration(<6 months) and remission within 6 months were positively associated. CONCLUSIONS: (Long-term) clinical outcomes differ between undifferentiated arthritis, autoantibody-negative and positive rheumatoid arthritis(RA). These data reconfirm that RA can be subdivided into aforementioned clinical phenotypes and that treatment might be stratified upon these phenotypes, although validation is needed. TRIAL REGISTRATION: ISRCTN, https://www.isrctn.com/, ISRCTN26791028.
34951180 [Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice]. 2021 Nov Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type â…¡ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.