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ID PMID Title PublicationDate abstract
33146518 Activity Prediction of Small Molecule Inhibitors for Antirheumatoid Arthritis Targets Base 2020 Dec 14 Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is compared to "immortal cancer" in industry. Currently, SYK, BTK, and JAK are the three major targets of protein tyrosine kinase for this disease. According to existing research, marketed and research drugs for RA are mostly based on single target, which limits their efficacy. Therefore, designing multitarget or dual-target inhibitors provide new insights for the treatment of RA regarding of the specific association between SYK, BTK, and JAK from two signal transduction pathways. In this study, machine learning (XGBoost, SVM) and deep learning (DNN) models were combined for the first time to build a powerful integrated model for SYK, BTK, and JAK. The predictive power of the integrated model was proved to be superior to that of a single classifier. In order to accurately assess the generalization ability of the integrated model, comprehensive similarity analysis was performed on the training and the test set, and the prediction accuracy of the integrated model was specifically analyzed under different similarity thresholds. External validation was conducted using single-target and dual-target inhibitors, respectively. Results showed that our model not only obtained a high recall rate (97%) in single-target prediction, but also achieved a favorable yield (54.4%) in dual-target prediction. Furthermore, by clustering dual-target inhibitors, the prediction performance of model in various classes were proved, evaluating the applicability domain of the model in the dual-target drug screening. In summary, the integrated model proposed is promising to screen dual-target inhibitors of SYK/JAK or BTK/JAK as RA drugs, which is beneficial for the clinical treatment of rheumatoid arthritis.
32615857 The influence of coffee intake and genetics on adenosine pathway in rheumatoid arthritis. 2020 Jul Aim: We studied the influence of coffee consumption on the therapeutic effect of methotrexate (MTX) in patients with rheumatoid arthritis (RA) sorted according to ADORA2A genotypes. Patients & methods: 82 RA patients were dichotomized according to caffeine intake with a threshold of 700 mg/week. Disease activity score 28 (DAS28) was applied (>3.2: high; <3.2: low or remission). Patients were genotyped using quantitative PCR allelic discrimination. Results: We found significantly higher risk of RA in patients with higher caffeine intake and the CT genotype of ADOARA2A rs2298383, rs3761422 and rs2267076 SNPs. The CC genotype of ADORA2A rs2236624 SNP in patients with lower caffeine intake treated with MTX is significantly protective. Conclusion: ADORA2A genotypes and coffee intake influence risk of RA and efficacy of it MTX treatment.
30572779 Age at the time of hip fracture in patients with rheumatoid arthritis is 4 years greater t 2020 Jan Objective: To investigate the characteristics of hip fractures in patients with rheumatoid arthritis (RA).Methods: Between 2012 and 2015, 789 hip fractures were treated at our hospital. Patients with RA were checked and their characteristics were compared with data recorded 10 years before, and with the general population.Results: There were 11 patients with RA, who were all female, and the mean age was 76 ± 7.0 years. The age at the time of hip fracture was 4 years older than that recorded 10 years before (72 ± 4.5 years, p < .05), but was younger than that of the general population (84 ± 8.0 years, p < .001). The mean prednisolone dose of 2.5 ± 2.6 mg/day was lower than that recorded 10 years before (4.8 ± 2.9 mg/day, p < .05). The rate of patients treated with anti-osteoporotic medications at fracture (73%) was higher than 10 years before (42%); however, the difference was not significant. The incidence of secondary fracture was not high compared to the general population. No mortality was recorded at 1 year, and no infective complications occurred.Conclusion: The age at the time of hip fracture in RA patients is increasing, but is still younger than that of the general population.
32496838 Unacceptable pain in the BARFOT inception cohort of patients with rheumatoid arthritis: a 2020 Sep Objectives: Pain is the most common and troublesome complaint in rheumatoid arthritis (RA). This study aimed to assess the prevalence and clinical implications of unacceptable pain in an inception cohort of patients with RA. Method: This study followed 477 patients from the BARFOT (Better Anti-Rheumatic FarmacOTherapy) early RA cohort for 15 years. Unacceptable pain was defined as ≥ 40 mm on a visual analogue scale for pain, while tolerable pain denoted no pain or pain below this cut-off, according to the patient acceptable symptom state concept. Results: Unacceptable pain was frequent. At the 15 year follow-up visit, 34% had unacceptable pain. Patients with unacceptable pain had, compared with patients with tolerable pain, significantly more disease activity, worse patient global assessment, and worse function on the Health Assessment Questionnaire and Signals of Functional Impairment, but the degree of joint destruction was similar. Disease-modifying anti-rheumatic drug treatment was similar, but patients with unacceptable pain were more often treated with corticosteroids. At 15 years, patients with unacceptable pain who were in remission (33%) had less inflammation and better function than those not in remission, suggesting the presence of non-inflammatory causes of pain. Conclusions: In this cohort of patients with RA, pain was frequent and severe, with negative effects on experienced health and function. Unacceptable pain was frequent and occurred also in patients in remission, indicating that pain in RA is multifactorial and should always be regarded as an important concern in itself. The cause of pain should be recognized and treated appropriately.
32324839 Antibodies to synthetic citrullinated peptide epitope correlate with disease activity and 2020 Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world's most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogen-derived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.
33254964 Fail-safe nano-formulation of prodrug of sulfapyridine: Preparation and evaluation for tre 2021 Jan Aim of the present study was to give a second life to the long-abandoned drug, sulfapyridine (SP) for its anti-arthritic potential by design of nano-vesicular delivery system. For this, intra-articular delivery of its liposomal formulation was tried. As the prepared formulation exhibited rapid drug leakage, an arthritis responsive prodrug of SP showing lability towards synovial enzymes was synthesized to exploit the over-expression of arthritis specific enzymes. Prodrug (SP-PD) exhibited better retention in liposomes as compared to the drug, preventing its escape from synovium. Hydrolysis of SP-PD in human plasma and synovial fluid indicated its high susceptibility to enzymes. The liposomes of SP-PD exhibited larger mean size, less PDI and higher zeta potential as compared to those for SP liposomes. In arthritic rats, prodrug liposomes were found to reverse the symptoms of inflammation, including the levels of biochemical markers. Liposomes of bio-responsive prodrug, therefore, offer a revolutionary approach in the treatment of rheumatoid arthritis.
33003645 Do Interventions with Diet or Dietary Supplements Reduce the Disease Activity Score in Rhe 2020 Sep 29 The aim was to compile the evidence from Randomized Controlled Trials (RCTs) of diet or dietary supplements used to reduce disease activity in adults with Rheumatoid Arthritis (RA). Searches were performed in the databases PubMed, Scopus and Cochrane. Only RCT studies of diets, foods or dietary supplements, looking at effects on the Disease Activity Score in 28 joints (DAS28) among adults with RA, published in peer-reviewed journals, were included. A total of 27 articles were included-three of whole diets (Mediterranean diet, raw food and anti-inflammatory diet), five of food items, five of n-3 fatty acids, five of single micronutrient supplements, four of single antioxidant supplements and five of pre-, pro- or synbiotics. Studies that showed moderate strength evidence for positive effects on disease activity in RA included interventions with a Mediterranean diet, spices (ginger powder, cinnamon powder, saffron), antioxidants (quercetin and ubiquinone), and probiotics containing Lactobacillus Casei. Other diets or supplements had either no effects or low to very low strength of evidence. In conclusion, RCT studies on diet or dietary supplements are limited in patients with RA, but based on the results in this review there is evidence that some interventions might have positive effects on DAS28.
31972422 Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and mo 2020 Mar Network pharmacology is a novel approach that uses bioinformatics to predict and identify multiple drug targets and interactions in disease. Here, we used network pharmacology to investigate the mechanism by which triptolide acts in rheumatoid arthritis (RA). We first searched public databases for genes and proteins known to be associated with RA, as well as those predicted to be targets of triptolide, and then used Ingenuity Pathway Analysis (IPA) to identify enriched gene pathways and networks. Networks and pathways that overlapped between RA-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in RA. The following proteins were found to occur in both RA-associated networks and triptolide target networks: CD274, RELA, MCL1, MAPK8, CXCL8, STAT1, STAT3, c-JUN, JNK, c-Fos, NF-κB, and TNF-α. Docking studies suggested that triptolide can fit in the binding pocket of the six top candidate triptolide target proteins (CD274, RELA, MCL1, MAPK8, CXCL8 and STAT1). The overlapping pathways were activation of Th1 and Th2 cells, macrophages, fibroblasts and endothelial cells in RA, while the overlapping networks were involved in cellular movement, hematological system development and function, immune cell trafficking, cell-to-cell signaling and interaction, inflammatory response, cellular function and maintenance, and cell death and survival. These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in RA. Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.
32769882 Discontinuation of biosimilar infliximab in Japanese patients with rheumatoid arthritis ac 2020 Aug 7 BACKGROUND: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I. METHODS/DESIGN: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13. DISCUSSION: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, clinical disease activity indices, MSUS findings, and serum biomarkers. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007.
33341117 Patient preferences on rheumatoid arthritis second-line treatment: a discrete choice exper 2020 Dec 19 BACKGROUND: Preference assessments of patients with rheumatoid arthritis can support clinical therapeutic decisions for including biologic and targeted synthetic medicines to use. This study assesses patient preferences for attributes of second-line therapies and heterogeneity within these preferences to estimate the relative importance of treatment characteristics and to calculate the minimum benefit levels patients require to accept higher levels of side effects. METHODS: Between November 2018 to August 2019, patients with rheumatoid arthritis were recruited to a survey containing demographic and disease-related questions as well as a discrete choice experiment to measure their preferences for second-line therapies using biologics or Janus kinases inhibitors. Treatment characteristics included were route of administration, frequency of use, probability of mild short-term side effects, probability of side effects changing appearance, probability of psychological side effects, probability of severe side effects and effectiveness of treatment. RESULTS: A total of 358 patients were included in the analysis. A latent class analysis revealed three preference patterns: (1) treatment effectiveness as the single most important attribute, (2) route of administration as the most important attribute, closely followed by frequency of use and psychological side effects and (3) severe side effects as the most important attribute followed by psychological side effects. In addition, disease duration and mild side effects influenced the patients' choices. CONCLUSION: Respondents found either effectiveness, route of administration or severe side effects as the most important attribute. Patients noting effectiveness as most important were more willing than other patients to accept higher risks of side effects.
32534200 Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese 2020 Dec OBJECTIVE: To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. METHODS: Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI]≤10) for≥12weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score>10 or intervention with rescue treatments for any reason even if the CDAI score was≤10. The impact of baseline characteristics on disease flare at week 64 (52weeks after methotrexate discontinuation) was assessed with logistic regression models. RESULTS: Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6-81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4weeks, or subcutaneously every 2weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80-115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72-83.80) were independent predictors of disease flare. CONCLUSION: Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. TRIAL REGISTRATION NUMBER: jRCTs041180071, UMIN000021247.
33099255 A hypothesis of bone joint defects. 2020 Dec The work presented proposes origins of the extensive range of observations concerning changes in bone joints associated with rheumatoid arthritis, osteoarthritis and arthritis urica. These changes are shown to originate with alterations of cell reactions involving four basic cell biochemicals. The proposals allow explanations of, for example, the link between rheumatoid arthritis and anaemia. It is also shown that performic acid is a presently unrecognised cause of degradation of tissue in bone joints. Suggestions are made as to means of control of these changes.
33255028 Au@polydopamine nanoparticles/tocilizumab composite as efficient scavengers of oxygen free 2021 Jan Rheumatoid arthritis (RA) is the most common chronic autoimmune disorder associated with high-cost, side effects, and low therapeutic effects. To improve the treatment of RA, we originally developed a novel anti-RA Au@polydopamine nanoparticles (PDANPs)/TCZ composite using PDANPs as the binding sites of gold nanoparticles (AuNPs) and the drug carries of tocilizumab (TCZ) through a facile and environmentally-friend method, aiming to effectively scavenge oxygen free radicals (OFR) and inhibit the formation of related inflammatory factors. Characterizations showed that AuNPs with the size of 11.4 ± 2.9 nm randomly distributed onto the surface of PDANPs (145.8 ± 31.9 nm), meanwhile TCZ was chemically cross-linked to PDANPs through Schiff base linkage. The synthesized composite had good biocompatibility that can promote the proliferation and growth of chondrocytes and fibroblasts. More importantly, Au@PDANPs/TCZ composite showed more excellent abilities to scavenge OFR and inhibit the related inflammatory factors in vitro and in vivo than that of AuNPs and PDANPs owing to the synergistic scavenging effect, ensuring its best therapeutic effect in RA therapy. This new composite will have application potential in the treatment of RA related disease.
33204694 Identifying Compound Effect of Drugs on Rheumatoid Arthritis Treatment Based on the Associ 2020 Rheumatoid arthritis (RA) is a chronic autoimmune disorder that is diagnosed mainly on the basis of patient signs, symptoms, and laboratory indices. However, the exact causes of RA are unclear. Moreover, there is a lack of any method of dynamically evaluating the efficacy of the medication administered to treat RA. Here, we applied a random walk model to reveal the compatibility among the various constituents of traditional Chinese medicine and evaluate their therapeutic efficacy against RA. Drugs commonly used to treat RA were investigated using cluster analysis. The association rule analysis was applied to identify compatibilities among the constituents. A random walk model was developed to evaluate drug efficacy based on an in-house database comprising the clinical records of 9,408 RA patients. Frequently administered medicines were combined into three correlated sets. The evaluation based on the random walk method showed that the drug combination improved ESR, CRP, C3, C4, and IgA more effectively than any single drug. The present study demonstrated that the TCM constituents complement each other and various combinations of them produce different therapeutic effects on RA treatment.
31562795 First Validation of the Full PROMIS Pain Interference and Pain Behavior Item Banks in Pati 2020 Nov OBJECTIVE: Pain interference and pain behavior are highly relevant outcomes in patients with rheumatoid arthritis (RA). The Patient-Reported Outcomes Measurement Information System (PROMIS) is a universally applicable set of item banks measuring patient-reported health, and if applied as computerized adaptive tests (CATs), more efficiently and precisely than current instruments. The objective was to study the psychometric properties of the Dutch-Flemish PROMIS pain interference (PROMIS-PI) and the PROMIS pain behavior (PROMIS-PB) item banks in patients with RA. METHODS: A total of 2,029 patients with RA completed the full PROMIS-PI (version 1.1, 40 items), and 1,554 patients completed the full PROMIS-PB (version 1.1, 39 items). The following psychometric properties were studied: unidimensionality, local dependence, monotonicity and graded response model (GRM) fit, cross-cultural validity (differential item functioning [DIF] for language [Dutch versus Flemish]), other forms of measurement invariance, construct validity, reliability, and floor and ceiling effects. RESULTS: The PROMIS-PI and PROMIS-PB banks were sufficiently unidimensional (Omega-hierarchical [Omega-H] 0.99, 0.95, and explained common variance 0.95, 0.78, respectively), had negligible local dependence (0.3-1.4% of item pairs), good monotonicity (H 0.75, 0.46), and a good GRM model fit (no misfitting items). Furthermore, both item banks showed good cross-cultural validity (no DIF for language), measurement invariance (no DIF for age, sex, administration mode, and disease activity), good construct validity (all hypotheses met), high reliability (>0.90 in the range of patients with RA), and an absence of floor and ceiling effects (0% minimum or maximum score, respectively). CONCLUSION: Both PROMIS-PI and PROMIS-PB banks showed good psychometric properties in patients with RA and can be used as CATs in research and clinical practice.
32621635 Autoantibodies to Malondialdehyde-Acetaldehyde Are Detected Prior to Rheumatoid Arthritis 2020 Dec OBJECTIVE: To examine serum autoantibodies to malondialdehyde-acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis. METHODS: Concentrations of anti-MAA antibody isotypes, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and IgM rheumatoid factor (IgM-RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed models for each antibody and/or isotype. Associations between prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models. RESULTS: Concentrations of IgG (log(2) difference 0.34) and IgA (log(2) difference 0.43) anti-MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively (P < 0.05 for both). There was no evidence of case-control divergence for IgM anti-MAA antibody concentration. Anti-CCP-2 and IgM-RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti-MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti-CCP-2 antibody and RF concentrations prior to diagnosis (β = 0.22-0.27 for IgM-RF; β = 0.44-0.93 for anti-CCP-2) (P < 0.001). CONCLUSION: IgG and IgA anti-MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti-CCP-2 or RF. These findings suggest that MAA formation and anti-MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.
32281166 The potential of circulating microRNA-125a and microRNA-125b as markers for inflammation a 2020 Aug OBJECTIVE: This study was to investigate the changes in circulating microRNA (miR)-125a and miR-125b during infliximab (IFX) treatment, and their value in predicting clinical response to IFX in rheumatoid arthritis (RA) patients. METHODS: The plasma samples were obtained from 96 active RA patients who underwent 24-week IFX treatment and from 96 healthy controls to detect miR-125a and miR-125b expressions by RT-qPCR. Clinical response was assessed according to EULAR criteria based on disease activity alleviation at week 4, week 12, and week 24. RESULTS: MiR-125a and miR-125b expressions were both elevated in RA patients compared with healthy controls, and they could differentiate RA patients from healthy controls by receiver operating characteristic curve analysis. Baseline miR-125a positively correlated with C-reactive protein (CRP) level; meanwhile, baseline miR-125b positively correlated with tender joint count (TJC), swollen joint count (SJC), erythrocyte sedimentation rate (ESR), CRP, and DAS28-ESR score in RA patients. With the 24-week IFX treatment, clinical response rate was gradually increased, while miR-125a and miR-125b expressions were gradually decreased in RA patients. At week 24, 69 (71.9%) patients responded to IFX treatment, while 27 (28.1%) patients did not respond to IFX treatment. Importantly, baseline miR-125a and miR-125b expressions were higher in responders than that in non-responders, further multivariate logistic regression analysis disclosed that miR-125b but not miR-125a could independently predict better clinical response to IFX in RA patients. CONCLUSION: Circulating miR-125a and miR-125b displays the potency for guiding personalized treatment strategy and improving clinical outcomes in RA patients.
32631453 Profiling of IgG antibodies targeting unmodified and corresponding citrullinated autoantig 2020 Jul 6 OBJECTIVE: To assess the diagnostic potential of IgG antibodies to citrullinated and corresponding native autoantigens in early arthritis. METHODS: IgG autoantibodies to 390 distinct unmodified and corresponding in vitro citrullinated recombinant proteins were measured by a multiplex assay in baseline blood samples from a German multicenter national cohort of 411 early arthritis patients (56.5 ± 14.6 years, 62.8% female). The cohort was randomly split into a training cohort (n = 329, 28.6% ACPA positive) and a validation cohort (n = 82, 32.9% ACPA pos.). The diagnostic properties of candidate antibodies to predict a subsequent diagnosis of rheumatoid arthritis (RA) as opposed to a non-RA diagnosis were assessed by receiver operating characteristics analysis and generalized linear modeling (GLM) with Bonferroni correction in comparison to clinically determined IgM rheumatoid factor (RF) and citrullinated peptide antibody (ACPA) status. RESULTS: Of 411 patients, 309 (75.2%) were classified as RA. Detection rates of antibody responses to citrullinated and uncitrullinated forms of the proteins were weakly correlated (Spearman's r = 0.13 (95% CI 0.029-0.22), p = 0.01). The concentration of 34 autoantibodies (32 to citrullinated and 2 to uncitrullinated antigens) was increased at least 2-fold in RA patients and further assessed. In the training cohort, a significant association of citrullinated "transformer 2 beta homolog" (cTRA2B)-IgG with RA was observed (OR 5.3 × 10(3), 95% CI 0.8 × 10(3)-3.0 × 10(6), p = 0.047). Sensitivity and specificity of cTRA2B-IgG (51.0%/82.9%) were comparable to RF (30.8%/91.6%) or ACPA (32.1%/94.7%). Similar results were obtained in the validation cohort. The addition of cTRA2B-IgG to ACPA improved the diagnostic performance over ACPA alone (p = 0.026 by likelihood ratio test). CONCLUSIONS: cTRA2B-IgG has the potential to improve RA diagnosis in conjunction with RF and ACPA in early arthritis.
32914483 The effect of black barberry hydroalcoholic extract on immune mediators in patients with a 2021 Feb Rheumatoid arthritis (RA) is an autoimmune disease associated with inflammation. In this trial, we aimed to investigate the Immunomodulatory effect of hydroalcoholic extract of black barberry on immune mediators in patients with active rheumatoid arthritis. In this randomized, double-blind, placebo-controlled clinical trial, 80 women with active RA were randomly assigned into two groups of two capsules, each containing 1,000 mg black barberry extract (n = 40) or maltodextrin placebo (n = 40) daily for 12 weeks. Demographic indices, physical activity, dietary intake, and disease activity were investigated using suitable questionnaires. Concentration of cytokines IL-2, IL-4, IL-10, and IL-17 in blood sample were measured using PBMC method. Statistical analysis was performed using SPSS (version 22). At baseline, there were no differences between the two groups in terms of demographic indices, physical activity, and dietary intake (p > .05). Black barberry supplementation reduced the severity of RA. It showed no significant effect on IL-2 and IL-4 cytokines (p > .05). IL-17 levels decreased significantly after the intervention within the black barberry group, while IL-10 had a significant increase in this group (p < .05). Barberry extract may reduce inflammatory and increase anti-inflammatory cytokines in RA, and stimulates the immune response by increasing Th2 production.
32013628 Identification of key biomolecules in rheumatoid arthritis through the reconstruction of c 2020 May Rheumatoid arthritis (RA) frequently seen chronic synovial inflammation causing joint destruction, chronic disability and reduced life expectancy. The pathogenesis of RA is not completely known. In this study, several gene expression data including synovial tissue and macrophages from synovial tissues were integrated with a holistic perspective and the molecular targets and signatures in RA were determined. Differentially expressed genes (DEGs) were identified from each dataset by comparing diseased and healthy samples. Afterward, the RA-specific protein-protein interaction (PPI) and the transcriptional regulatory network were reconstructed by using several biomolecule interaction data. Key biomolecules were determined through a statistical test employing the hypergeometric probability density function by using the physical interactions of transcriptional regulators and PPI. The integrative analyses of DEGs indicated that there were 110 and 494 common genes between synovial tissues and macrophages related datasets, respectively. Common DEGs of all datasets were identified as 25 genes and these core genes which might be feasible to uncover the mutual biological mechanism insights behind the RA pathogenesis were used for disease specific biological networks reconstruction. It was determined the hub proteins, novel key biomolecules (i.e. receptor, transcription factors and miRNAs) and biomolecules interactions by using the core DEGs. It was identified STAT1, RAC2 and KYNU as hub proteins, PEPD as a receptor, NR4A1, MEOX2, KLF4, IRF1 and MYB as TFs, miR-299, miR-8078, miR-146a, miR-3659 and miR-6882 as key miRNAs. It was determined that biomolecule interaction scenarios using identified key biomolecules and novel biomolecules including RAC2, PEPD, NR4A1, MEOX2, miR-299, miR-8078, miR-3659 and miR-6882 in RA. Our novel findings could be a crucial resource for the understanding of RA molecular mechanism and may be considered as drug targets and development of novel diagnostic strategies. Corresponding genes and miRNAs should be validated via experimental studies.