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ID PMID Title PublicationDate abstract
34369364 Prognostic signature of interferon-γ and interleurkin-17A in early rheumatoid arthritis. 2022 May OBJECTIVES: CD4+ T cells are crucial for the pathogenesis of rheumatoid arthritis (RA). Here, we evaluated gene expression in CD4+ T cells in early RA, and main purpose of present study was to seek the changes in CD4+ T-cell-related cytokines according to RA progression. METHODS: Early RA was defined as methotrexate (MTX)-naïve patients. Established RA was defined as patients with more than 6 months of DMARDs. Patients with osteoarthritis were evaluated as controls. Microarray analysis was used to identify overexpressed genes in CD4+ T cells, and RT-qPCR was used to validate. Plasma cytokine were measured in patients with early and established RA, and correlations with disease activity were assessed in patients with early RA, whereas clinical prognosis was assessed in established patients with RA. RESULTS: Thirty-four genes showed overexpression in CD4+ T cells from patients with early RA compared with OA controls. Nineteen were related to interferon (IFN)-γ, and eight were related to interleukin (IL)-17A. Plasma levels of IL-17A, IL-6, IL-12, and TNF-α correlated with IFN-γ, and correlation coefficient was highest between DAS28-ESR and plasma IFN-γ levels in patients with early RA (Rho=0.553, p=0.0025). In established RA with low disease activity, drug reduction group showed lower plasma IFN-γ and IL-17A than drug maintenance/relapse group (13.61±5.75 vs. 29.89±18.72, p<0.001; and 10.91±3.92 vs. 21.04±12.81 pg/mL, p<0.001, respectively). CONCLUSIONS: The IFN-γ and IL-17 gene signature in CD4+ T cells was significantly increased in early RA. Patients with established RA with low levels of IFN-γ and IL-17A could be eligible for dose reduction.
35318077 Angelica sinensis polysaccharide improves rheumatoid arthritis by modifying the expression 2022 Jun 1 Rheumatoid arthritis (RA) is an autoimmune disease with a high incidence. Recent studies have demonstrated that diet can contribute to the development and progression of RA. Indeed, non-starch polysaccharides (NSPs) were known to be related to the improvement of RA. In this study, the collagen-induced rats were administrated with Angelica sinensis polysaccharide (ASP) at 200 mg/kg (L), 400 mg/kg (M), or 800 mg/kg (H). Results showed that ASP could reduce joint swelling and significantly inhibit anti-CII-antibodies and pro-inflammatory factors in RA, H group showed the best treatment among them. Further analysis using 16S rDNA sequencing suggested that ASP could shape the gut microbiota composition. Several key bacteria, including norank_f__norank_o__Clostridia_UCG-014, Lactobacillus, norank_f__Oscillospiraceae, and norank_f__Desulfovibrionaceae, were found to be related to the development of RA. The colonic transcriptome showed that ASP could restore RA-induced intestinal dysfunction, such as tight junction disarrangement, by upregulating Cldn5. The balance between osteoblasts and osteoclasts might be modified by regulating the expression of Slit3 and Rgs18 to alleviate RA, which may be correlated with gut microbiota. Our results suggested that ASP improved RA by regulating gut microbiota and gene expression, revealing a positive relationship between dietary patterns and RA.
35328849 Telemedicine in the Management of Patients with Rheumatic Disease during COVID-19 Pandemic 2022 Mar 8 The management of patients with immuno-rheumatological diseases has profoundly changed during the COVID-19 pandemic and telemedicine has played an important role in the disease follow-up. In addition to monitoring disease activity and any adverse events, especially infectious events, assessing the psychological situation of the patient can be fundamental. Furthermore, COVID-19 has a serious impact on mental health and, since the beginning of the pandemic, a significantly higher incidence of anxiety disorders and depressive symptoms especially in younger people was observed. In this study, we evaluated the incidence of depressive disorders, anxiety, and fibromyalgia (FM) in our patients with rheumatoid arthritis and psoriatic arthritis during the lockdown period due to the COVID-19 pandemic and we validate the use of telemedicine in the clinical management of these patients. Mental and physical stress during the COVID-19 pandemic can greatly worsen FM symptoms and intensify patients' suffering without a clinical flare of the inflammatory disease for patients affected by rheumatoid arthritis. Telemedicine has allowed us to identify patients who needed a face-to-face approach for therapeutic reevaluation even if not related to a flare of the inflammatory disease. Even if our data does not allow us to draw definitive conclusions regarding the effectiveness of telemedicine as greater than or equal to the standard face-to-face approach, we continue to work by modifying our approach to try to ensure the necessary care in compliance with safety and, optimistically, this tool will become an important part of rheumatic disease management.
34489175 Pain and Affected Symptoms of Patients with Rheumatoid Arthritis During COVID-19 Period. 2022 Feb BACKGROUND: Aim: The aim of this study is to determine the symptoms, pain, and function changes experienced by rheumatoid arthritis patients during the COVID-19 pandemic. METHOD: This descriptive study was completed with a total of 119 patients from the rheumatology clinic of a university hospital who met the follow-up research criteria and agreed to participate in the study. Descriptive features question form, pandemic period disease characteristics form, and Visual Analogue Scale were used to collect data. RESULTS: The mean age of the patients was 48.53 ± 10.24, the duration of the disease was 69.63 ± 37.02 months, the average visual analog scale values before the pandemic period were 3.77 ± 1.40, while the average visual analog scale values during the pandemic period were 5.02 ± 1.57. The most common patient complaints were hygiene problems (p < .001), dressing problems (p < .001), and nutritional problems (p < .001) due to increased pain during the pandemic period. It was determined that the patients needed a health care professional for self-care (p < .001), injections (p < .001), and pain management (p < .001) during the pandemic period. CONCLUSIONS: During the pandemic period, patients with rheumatoid arthritis (RA) stated that they needed the support of a health care professional for self-care, injections, and pain management.
35363175 Rheumatoid arthritis in a patient with compound heterozygous variants in the COL11A2 gene 2022 Feb 18 RATIONALE: Collagen type XI alpha 2 chain is a component of type XI collagen and is expressed in various tissues including articular cartilage and tectorial membrane of the cochlea. Variants in the COL11A2 gene, which encodes collagen type XI alpha 2 chain, has been reported to cause hearing loss and has been associated with osteoarthritis and ossification of the posterior longitudinal ligament of the spine. Despite the importance of type XI collagen in the joints, association of rheumatoid arthritis (RA) with COL11A2 has not been reported. PATIENT CONCERNS: The patient is a 60-year-old female, born to Japanese parents of no known consanguinity. She had progressive hearing loss since childhood. Her father also had progressive hearing loss before middle age. She developed joint pain in the knees and the hips in her forties. When she was 56, she developed polyarthritis. Rheumatoid factor and anti-CCP antibodies were positive. DIAGNOSES: She was diagnosed with osteoarthritis and RA. Whole exome analysis detected 2 rare variants, c.4201C>T, p.(Arg1401Trp) and c4265C>T, p.(Pro1422Leu), in the COL11A2 gene (NM_080680.2). Whole genome analysis with a long insert size confirmed 2 variants that are in trans. INTERVENTIONS AND OUTCOMES: She received a cochlear implant, which improved her hearing. She was treated with methotrexate, golimumab, tocilizumab, and upadacitinib with partial responses for her RA. LESSONS: We herein report a patient with RA with compound heterozygous variants in the COL11A2 gene. Autoantibodies against type XI collagen are detected in the sera of patients with RA, suggesting the possibility that type XI collagen may be involved in the pathogenesis of RA as an autoantigen. The hearing loss and osteoarthritis in this patient may be due to the compound heterozygous variants in the COL11A2 gene, and the conformational changes induced by the variants may have changed the immunogenicity of type XI collagen, leading to the development of RA.
34953451 The effect of Swedish massage on pain in rheumatoid arthritis patients: A randomized contr 2022 Feb BACKGROUND AND PURPOSE: Joint pain is one of the most common symptoms in rheumatoid arthritis patients and require medical attention. The purpose of this study was to assess the effects of Swedish massage on pain and painkiller consumption in rheumatoid arthritis patients. MATERIALS AND METHODS: A total of 60 patients participated in the experiment, with half assigned to the control group (n = 30) and half to the experimental (n = 30) group using the block randomization method. On patients in the experimental group, a 30-min Swedish massage was performed regularly for eight weeks: twice a week for the first four weeks, and three times a week for the last four weeks. The control group received routine care. The visual analogue scale-pain was used to measure pain in the two groups at three points of time: before the beginning of the experiment, immediately after the last session, and one month after the last session of the intervention. RESULTS: The analysis of covariance showed that there were significant differences between the two groups' mean scores of pain and painkiller consumption immediately after and one month after the last session of the intervention (p = 0.01). Furthermore, in the experimental group, the mean scores of pain and painkiller consumption decreased over the three points of time (p < 0.05). CONCLUSION: Swedish massage can be effective in reducing pain and the need to use painkillers in rheumatoid arthritis patients.
34992007 Small airway disease and its predictors in patients with rheumatoid arthritis. 2022 May BACKGROUND: Rheumatoid arthritis (RA) is a connective tissue disease, characterized by symmetric peripheral polyarthritis. Extra-articular disease occurs in approximately 50% of the patients with lung being a common site. The presence of functional or morphological abnormalities in small airways has recently been noted in patients with RA but its exact prevalence and clinical significance is still a subject of debate. This study was aimed to determine the prevalence of small airway disease (SAD) in patients with RA and the factors influencing it. METHODS: Fifty consecutive patients with RA were included in this cross-sectional observational study. All patients were subjected to pulmonary function tests (PFT) including Spirometry and Forced Oscillation technique (FOT). Those with features of SAD on PFT were subjected to High-Resolution Computed Tomography (HRCT) of the chest. RESULTS: Spirometry was suggestive of SAD in 17 patients, with 34% prevalence and FOT was abnormal in 9 patients, with 18% prevalence in the study population. Of 17 patients with SAD on spirometry, 8 (47.05%) patients showed mosaic attenuation, a sign of SAD on the HRCT chest. On univariate analysis, age, Disease Activity Score (DAS-28), joint erosions on X-ray, RF and anti-CCP were found to be associated with SAD. CONCLUSION: SAD was present in one-third of the patients with RA, even in those with short duration of disease, low to moderate disease activity and no respiratory symptoms. It is thus inferred that the complete workup of RA patients should include pulmonary function assessment.
34182890 No difference in antidepressant prescription in rheumatoid arthritis and controls. Results 2022 May OBJECTIVE: Depression occurs at least two times more often in rheumatoid arthritis (RA) patients than in controls, but little is known about the treatment of depression in RA. The primary objective of this study was to compare the 1 year period prevalence of antidepressant prescription in patients with RA versus controls. METHOD: We included a retrospective inception cohort of 509 patients with incident RA and 2545 frequency-matched population controls ascertained from 1995 to 2002. The cohort was followed until 31 December 2017 and linked with nationwide Danish registers. From the Danish National Prescription Register, we obtained information on redeemed prescriptions of antidepressants (Anatomical Therapeutic Chemical code N06A). RESULTS: We did not demonstrate significant differences in the 1 year period prevalence ratios and the incidence rate ratios for either antidepressant prescription or the frequency of hospital admissions with depressive episode. The most frequent indication for antidepressant prescription in patients with RA was depression. Cox regression analyses showed no association between RA and antidepressant prescription. CONCLUSION: We found no significant differences in the occurrence of antidepressant prescription in patients with RA versus matched controls. The main indication for antidepressant prescription in RA was depression.
34054072 Cardiovascular Risk Assessment in Women With Rheumatoid Arthritis Through Carotid and Femo 2022 Mar 1 OBJECTIVE: The aims of this study were to assess cardiovascular risk in patients with rheumatoid arthritis (RA) classified as low-risk by the Framingham score, before and after the multiplication by 1.5 recommended by the European League Against Rheumatism (EULAR), and to stratify them using carotid and femoral Doppler ultrasound (DUS) in order to optimize the assessment of the asymptomatic cardiovascular disease incidence. METHODS: Thirty-five female patients with RA and 35 healthy women (control group), both with low cardiovascular risk by Framingham score, were enrolled in the study (randomized). All of them underwent carotid and femoral DUS studies. RESULTS: The mean age at diagnosis was 44.57 years, the mean disease duration was 12.11 years and the mean disease activity score according to the Disease Activity Score 28 was 1.91, whereas according to the Clinical Disease Activity Index, it was 6.176. The sample was homogeneous. Within the RA group, 46% showed changes in the carotid and/or femoral DUS, compared with 14% in the control group (p = 0.004). Of the DUS with abnormalities, in the RA group, 31% of the carotid DUS and 81% of the femoral DUS (p = 0.005) showed intima-media thickness and/or atherosclerotic plaques. After EULAR 1.5 multiplication factor, 66% remained low cardiovascular risk. Of these, 35% of the patients showed changes in the carotid and/or femoral DUS, compared with 14% of the control group (p = 0.07). CONCLUSIONS: The EULAR criteria are effective at identifying patients with high cardiovascular risk. Carotid DUS and, especially, femoral DUS are tools that can be used in clinical practice as ways to detect CVD even in its asymptomatic form.
35270781 Sexual Dysfunction and Quality of Life in Patients with Rheumatoid Arthritis. 2022 Mar 6 BACKGROUND: Sexual health is a major component of human well-being. As repeatedly shown in research, satisfaction with sex life and sexual fulfillment correlate positively with quality of life (QoL) in most of its aspects. It is thus true that a reduced quality of one's sex life and lack of sexual fulfillment can contribute to poorer QoL overall. The aim of this study is to describe an assessment of sexual dysfunction and factors affecting sexual dysfunctions of patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: 171 consecutive RA patients (mean age 48.3 ± 14.6) attending the rheumatology outpatient clinic. Standardized questionnaires used in the study were the sexological questionnaire, WHOQOL-BREF to assess QoL level, Disease Acceptance Scale, and VAS scale to assess pain intensity. RESULTS: The mean duration of the disease in the study group was 13 ± 9 years, mean score of subjective assessment of mobility was 6.2 ± 1.6, and the mean score of the DAS-28 was 4.0 ± 1.9. The study group presented a mean level of disease acceptance (AIS 29.6 ± 11.6). The comparative analysis showed significant differences in reaching orgasm and declared sexual dysfunctions. These problems occurred more often in women than in men (34.2% vs. 18% and 43% vs. 40%, respectively). In univariate analysis, factors correlating positively with the frequency of declaring sexual dysfunction were subjective motor score less < 6 points, AIS < 36 points, WHOQOL-BREF < 59 points, disease activity ≥3.5 points, and VAS > 3. In multivariate logistic regression analysis, independent factors positively correlating with frequency of sexual dysfunction declaration were general QoL (β = 1.255; p = 0.035) and pain limiting social life (β = 1.564; p = 0.030). The absence of comorbidities correlated negatively and reduced the prevalence of sexual dysfunction (β = -1.030; p = 0.043). Patients with reduced QoL and patients with pain limiting social life had 3.5 and 4.8 times higher risk of sexual dysfunction than other patients, respectively. In contrast, those without comorbidities were 2.8 times more likely to be free of sexual dysfunction than those diagnosed with other chronic diseases besides RA. CONCLUSIONS: Sexual dysfunction is an emerging problem in both men and women with RA. The absence of comorbidities is an independent determinant of sexual dysfunction, whereas poor QoL and pain limiting social life are independent determinants that exacerbate sexual dysfunction in both genders.
35534493 RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vacci 2022 May 9 Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.
35634962 Symptomatic femoral head necrosis in patients with rheumatoid arthritis: A retrospective c 2022 Jun OBJECTIVE: We conducted a retrospective case-control study to investigate the risk factors for osteonecrosis of the femoral head (ONFH) in rheumatoid arthritis (RA) patients. METHODS: The clinical data of patients diagnosed with RA at Fujian Provincial Hospital from January 2013 to December 2020 were retrospectively collected and evaluated. Twenty-two patients with ONFH were identified. Eighty-eight age-, sex-, and disease duration-matched RA patients without symptomatic ONFH were randomly selected as controls in a ratio of 1:4. Logistic regression analysis was used to analyze the risk factors. RESULTS: The anticardiolipin (ACL)-immunoglobulin G (IgG) concentration, clinical disease activity index, simplified disease activity index, incidence of hyperlipidemia in the case group were higher than those in the control group. Multivariate logistic regression analysis did not find the independent risk factor in ONFH patients with RA. CONCLUSION: The pathogenesis of ONFH in RA is related to many factors such as ACL IgG, disease activity index, and hyperlipidemia. While, we went to great lengths to explore the relationship between antiphospholipid antibodies and ONFH, but it plays a very small role.
34929705 Assessment of the Ovarian Reserve by Serum Anti-Müllerian Hormone in Rheumatoid Arthritis 2022 BACKGROUND: The ovarian reserve has been reported to be diminished in patients with rheumatoid arthritis. However, these results are still controversial. Anti-Müllerian hormone (AMH) is considered a reliable biomarker for the ovarian reserve. We thus performed a meta-analysis to evaluate the AMH levels and the effect of DMARDs on the ovarian reserve in rheumatoid arthritis patients. METHODS: PubMed, EMBASE, the Cochrane Library, and 2 Chinese databases (CNKI and Wanfang database), up to September 2021, were searched for relevant studies. The Newcastle-Ottawa scale (NOS) was used to assess the quality of the included studies. Pooled standard mean difference (SMD) with 95% confidence intervals (CIs) were determined with the random-effects model. The heterogeneity was described by I2 statistic and p value from the Cochrane Q test. RESULTS: Eight eligible studies (679 patients and 1,460 controls) were included in the meta-analysis. Compared with healthy control, the AMH levels in RA patients were significantly lower with the pooled SMD of -0.40 (95% CI: -0.66 to -0.14). However, in comparison of AMH with and without DMARD treatment, there was no significant difference with the pooled SMD of -0.1 (95% CI: -0.39 to 0.19). CONCLUSION: The results indicated that there was an increased risk of ovarian failure in RA patients and which is not related to DMARD treatment.
35016729 SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the C 2022 Jan 11 OBJECTIVES: A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. METHODS: The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. RESULT: For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16-1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. CONCLUSIONS: SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.
35149777 UGT1A1 genetic variants are associated with increases in bilirubin levels in rheumatoid ar 2022 May Sarilumab is a human monoclonal antibody against interleukin (IL)-6Rα that has been approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) and an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). Mild liver function test abnormalities have been observed in patients treated with sarilumab. We describe a genome-wide association study of bilirubin elevations in RA patients treated with sarilumab. Array genotyping and exome sequencing were performed on DNA samples from 1075 patients. Variants in the UGT1A1 gene were strongly associated with maximum bilirubin elevations in sarilumab-treated patients (rs4148325; p = 2.88 × 10(-41)) but were not associated with aminotransferase elevations. No other independent loci showed evidence of association with bilirubin elevations after sarilumab treatment. These findings suggest that most bilirubin increases during sarilumab treatment are related to genetic variation in UGT1A1 rather than underlying liver injury.
34781416 Tissue engineered skeletal muscle model of rheumatoid arthritis using human primary skelet 2022 Feb Rheumatoid arthritis (RA) is a chronic inflammatory disease primarily targeting the joints. Autoreactive immune cells involved in RA affect other tissues, including skeletal muscle. Patients with RA experience diminished physical function, limited mobility, reduced muscle function, chronic pain, and increased mortality. To explore the impact of RA on skeletal muscle, we engineered electrically responsive, contractile human skeletal muscle constructs (myobundles) using primary skeletal muscle cells isolated from the vastus lateralis muscle of 11 RA patients (aged 57-74) and 10 aged healthy donors (aged 55-76), as well as from the hamstring muscle of six young healthy donors (less than 18 years of age) as a benchmark. Since all patients were receiving treatment for the disease, RA disease activity was mild. In 2D culture, RA myoblast purity, growth rate, and senescence were not statistically different than aged controls; however, RA myoblast purity showed greater variance compared to controls. Surprisingly, in 3D culture, contractile force production by RA myobundles was greater compared to aged controls. In support of this finding, assessment of RA myofiber maturation showed increased area of sarcomeric α-actinin (SAA) expression over time compared to aged controls. Furthermore, a linear regression test indicated a positive correlation between SAA protein levels and tetanus force production in RA and controls. Our findings suggest that medications prescribed to RA patients may maintain-or even enhance-muscle function, and this effect is retained and observed in in vitro culture. Future studies regarding the effects of RA therapeutics on RA skeletal muscle, in vivo and in vitro, are warranted.
34380068 Circulating Mir-140 and leptin improve the accuracy of the differential diagnosis between 2022 Jan The differential diagnosis of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) is difficult because of the lack of diagnostic clinical signs and reliable biomarkers. This study investigated microRNAs (miRNA) and adipokines as potential additional markers to discriminate PsA from RA. The expression profile of miRNA (miR-21, miR-140, miR-146a, miR-155, miR-181b, miR-223, miR-let-7e) and inflammatory cytokines (IL-1β, IL-6, IL-17a, IL-23a, TNF-α) from peripheral blood mononuclear cells of PsA and RA patients compared to healthy controls (HC) were evaluated by real-time PCR, and serum adipokines (adiponectin, chemerin, leptin, resistin, visfatin) and cytokines by ELISA assay. Univariable binary logistic regression was used to find the association between PsA and potential predictors. The gene expression of miRNA and cytokines and the serum levels of adipokines were found significantly different in PsA and RA patients compared to HC, as well as in PsA versus RA. MiR-140 gene expression resulted up-regulated in PsA patients and reduced in RA in comparison to HC, and, for the first time, significantly higher in PsA compared with RA. Serum levels of IL-23a and leptin were significantly increased in PsA and RA populations than in HC, as well as in PsA versus RA. Furthermore, circulating TNF-α was up-regulated in PsA and RA in comparison to controls, while resulted higher in RA than in PsA. Univariable binary logistic regression analysis found the above-mentioned markers associated to PsA versus RA. Our results first demonstrated an increased expression of circulating miR-140 and serum leptin in PsA patients compared to RA, which were identified as potential additional biomarkers to discriminate PsA from RA. Since the differential diagnosis of PsA and RA poses challenges in clinical practice, our data may help to enhance the diagnostic performance of PsA in daily practice.
34841538 Antcin K inhibits VEGF-dependent angiogenesis in human rheumatoid arthritis synovial fibro 2022 Jan Antrodia cinnamomea is a well-known medicinal mushroom in Taiwan that exhibits anti-inflammatory biological activities. In rheumatoid arthritis (RA), chronic inflammation and angiogenesis driven by proinflammatory cytokines reflect the severity of the disease. Although biological treatments have improved the outlook for RA, no healing exists. Moreover, the available pharmacotherapies do not work for all patients and drug safety is a major consideration. Investigations into plant-based medicines hope to reveal better, more tolerable agents. We examined whether Antcin K, a phytosterol isolated from A. cinnamomea, has anti-angiogenic activity in RA. The GSE12021 gene dataset from the Gene Expression Omnibus (GEO) database was examined for levels of vascular endothelial growth factor (VEGF) expression in 10 RA and 10 osteoarthritis (OA) synovial tissue samples. In clinical samples, VEGF expression was analyzed by immunohistochemical staining and ELISA in normal and RA synovial tissue, as well as OA and RA synovial fluid. Collagen-induced arthritis (CIA) and control tissue was stained with hematoxylin and eosin (H&E) for histological changes; Safranin O/Fast Green staining examined histopathological changes and evidence of bone erosion. Human RA synovial fibroblasts (RASFs) were incubated with Antcin K and cell viability was examined by the MTT assay. VEGF mRNA expression was detected in RASFs using qPCR. Antcin K significantly inhibited VEGF expression and ameliorates endothelial progenitor cell (EPC) migration and tube formation in RASFs by downregulating the phospholipase C-γ/protein kinase C-α pathway. Antcin K also induced anti-angiogenic effects in human RASFs without cytotoxicity. PRACTICAL APPLICATIONS: Analysis of GEO dataset samples and human synovial fluids or synovial tissues revealed higher VEGF levels in rheumatoid arthritis (RA) samples compared with osteoarthritis (OA) and healthy control samples. VEGF levels were also higher in mice with collagen-induced arthritis (CIA) than in healthy controls. Antcin K markedly suppressed VEGF expression in human RA synovial fibroblasts and inhibited the migration and tube formation of epithelial progenitor cells (EPCs) by downregulating the phospholipase C-γ/protein kinase C-α pathway. Further investigations are warranted to examine the effects of Antcin K in other angiogenesis-associated disorders.
34897494 Risk of herpes zoster in patients with rheumatoid arthritis in the biologics era from 2011 2022 Apr 18 OBJECTIVES: To elucidate the incidence and risk factors of herpes zoster (HZ) in patients with rheumatoid arthritis (RA) in the biologics era. METHODS: We determined the rate of HZ occurrence among the RA patients that participated in the Institute of Rheumatology, Rheumatoid Arthritis surveys from 2011 to 2015, by assessing medical records. The standardised incidence rate per 1000 patient-years with a 95% confidence interval (CI) was calculated, and risk factors for HZ were analysed using a time-dependent Cox regression analysis. RESULTS: Among 7815 patients (female, 84.7%) contributing to 25,863 patient-years of observation, 340 HZ events in 309 patients were confirmed. The standardised incidence rate (95% CI) per 1000 patient-years was 8.5 (6.9-10.5) in total, 6.0 (3.7-9.2) in men, and 11.0 (8.7-13.7) in women. Risk factors for HZ were age per 10 years (hazard ratio 1.14, 95% CI 1.03-1.26, p < .05), Japanese version of the Health Assessment Questionnaire (J-HAQ) score of 0.5-1.5 (versus J-HAQ = 0; 1.51, 1.09-2.10, p < .05), methotrexate use (1.58, 1.06-2.36, p < .05), and biologic use (1.88, 1.44-2.47, p < .01). CONCLUSIONS: In the era when biologics were frequently used and corticosteroid use and doses were decreasing, methotrexate and biologics increased the risk for HZ.
35566100 Gene Interaction Network Analysis Reveals IFI44L as a Drug Target in Rheumatoid Arthritis 2022 Apr 25 OBJECTIVE: Despite extensive research on periodontitis and rheumatoid arthritis, the underlying molecular connectivity between these condition remains largely unknown. This research aimed to integrate periodontitis and rheumatoid arthritis gene expression profiles to identify interconnecting genes and focus to develop a common lead molecule against these inflammatory conditions. MATERIALS AND METHODS: Differentially expressed genes (DEGs) of periodontitis and rheumatoid arthritis were identified from the datasets retrieved from the Gene Expression Omnibus database. The network was constructed by merging DEGs, and the interconnecting genes were identified and ranked using GeneMANIA. For the selected top ranked gene, the potential inhibitor was searched using FINDSITE(comb)2.0. Subsequently, the molecular docking and molecular dynamics were performed to determine the binding efficiency and protein-ligand complex stability, respectively. RESULTS: From the network analysis, IFN-induced protein 44-like (IFI44L) was identified as a top ranked gene involved in most of the immunological pathway. With further virtual screening of 6507 molecules, vemurafenib was identified to be the best fit against the IFI44L target. The binding energy and stability of IFI44L with vemurafenib were investigated using molecular docking and molecular dynamics simulation. Docking results show binding energy of -7.7 Kcal/mol, and the simulation results show stability till 100 ns. CONCLUSIONS: The identified IFI44L may represent a common drug target for periodontitis and rheumatoid arthritis. Vemurafenib could be a potent anti-inflammatory drug for both diseases.