Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30194490 [The knee joint in rheumatoid arthritis-current orthopaedic surgical treatment options]. 2018 Dec The knee joint is often involved in rheumatoid arthritis. Despite ever-improving medical antirheumatic therapies, surgical treatment continues to play an important role in optimal multidisciplinary care. The aim of the present work is to process current orthopedic surgical therapy procedures on the knee joint according to disease stage. In the early phase, joint-preserving arthroscopic procedures for synovectomy are used. In advanced joint destruction, joint function can be restored by total knee arthroplasty. Of central importance for optimal patient care are individual treatment and good interdisciplinary coordination of all involved specialist groups.
30114200 Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by 2018 OBJECTIVE: To determine whether the expression of IL17A and CD21L genes in inflamed rheumatoid synovia is associated with the neogenesis of ectopic lymphoid follicle-like structures (ELS), and if this aids the stratification of rheumatoid inflammation and thereby distinguishes patients with rheumatoid arthritis that might be responsive to specific targeted biologic therapies. METHODS: Expression of IL17A and CD21L genes was assessed by RT-PCR, qRT-PCR and dPCR in synovia from 54 patients with rheumatoid arthritis. A subset of synovia (n = 30) was assessed by immunohistology for the presence of CD20+ B-lymphocytes and size of CD20+ B-lymphocyte aggregates as indicated by maximum radial cell count. The molecular profiles of six IL17A+/CD21L+ and six IL17A-/CD21L- synovia were determined by complementary DNA microarray analysis. RESULTS: By RT-PCR, 26% of synovia expressed IL17A and 52% expressed CD21L. This provided the basis for distinguishing four subgroups of rheumatoid synovia: IL17A+/CD21L+ (18.5% of synovia), IL17A+/CD21L- (7.5%), IL17A-/CD21L+ (33.3%) and IL17A-/CD21L- (40.7%). While the subgroups did not predict clinical outcome measures, comparisons between the synovial subgroups revealed the IL17A+/CD21L+ subgroup had significantly larger CD20+ B-lymphocyte aggregates (P = 0.007) and a gene expression profile skewed toward B-cell- and antibody-mediated immunity. In contrast, genes associated with bone and cartilage remodelling were prominent in IL17A-/CD21L- synovia. CONCLUSIONS: Rheumatoid synovia can be subdivided on the basis of IL17A and CD21L gene expression. Ensuing molecular subgroups do not predict clinical outcome for patients but highlight high inflammation and the predominance of B-lymphocyte mediated mechanisms operating in IL17A+/CD21L+ synovia. This may provide a rationale for more refined therapeutic selection due to the distinct molecular profiles associated with IL17A+/CD21L+ and IL17A-/CD21L- rheumatoid synovia.
29734142 Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthri 2018 BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. METHODS: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. RESULTS: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. CONCLUSION: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.
30314410 Effects of human cyclooxygenase-2 gene silencing on synovial cells of rheumatoid arthritis 2018 The aim of the study is to screen the effective shRNA sequence which can silence the human COX-2 expression level in synovial cells of rheumatoid arthritis (RA) patient transfected by the lentivirus. Four pairs of hCOX-2 shRNA were designed and inserted into lentivirus to form pGPHI/GFP/Neo-shRNA vector. The reconstructed virus was transfected into synovial cells derived from RA patients, and then the expression level of hCOX-2 mRNA and the protein of the inflammatory factors including prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), interleukin-1β (IL-1β) and tumour necrosis factor alpha (TNF-α) in the supernatants were examined with real-time PCR and ELISA, respectively. There was no obvious negative influence on cell growth and morphology after hCOX-2 shRNA gene transfection mediated by lentivirus. The hCOX-2 mRNA expression level, as well as the concentration of PGE2, VEGF, IL-1β and TNF-α, decreased significantly (p < .05). RNAi mediated by lentivirus can significantly inhibit hCOX-2 mRNA expression level in synovial cells of RA patients, so as to reduce the expression of inflammatory cytokines.
29595700 Starting of biological disease modifying antirheumatic drugs may be postponed in rheumatoi 2018 Mar The objective of this study was to assess the frequency of comorbidities and multimorbidities in rheumatoid arthritis (RA) patients under biologic therapy and their effects on biological disease modifying antirheumatic drugs (DMARDs) choice, timing, and response.Hacettepe University Biologic Registry (HUR-BIO) is single center biological DMARD registry. Cardiovascular, infectious, cancer, and other comorbidities were recorded with face to face interviews. Multimorbidity is defined as >1 comorbidity. Disease duration, initial date of biological DMARDs, initial and overall biological DMARD choice were recorded. Disease activity score-28 (DAS-28) responses were compared to comorbidity presence and multimorbidity.Total of 998 RA patients were enrolled into the study. The mean age was 53.1 (12.5) and mean disease duration (standard deviation [SD]) was 11.7 (7.5) years. At least 1 comorbidity was detected in 689 (69.1%) patients, 375 (37.9%) patients had multimorbidity. Patients had mean 1.36 ± 1.32 comorbidity. The median durations of first biological DMARDs prescription were 60 (3-552) months after RA diagnosis. For multimorbidity patients, the median first biological prescription duration was longer than the duration for patients without multimorbidity (72 [3-552] vs 60 [3-396] months, P < .001). The physicians prescribe tumor necrosis factor inhibitor (TNFi) biological drugs less frequently than other biological DMARDs in patients with at least 1 comorbidity (66.2% vs 74.5%, P = .007) or multimorbidity (34.6% vs 43.5%, P = .006). Patients with comorbidities and multimorbidity achieved DAS-28 remission less frequently than patients without comorbidity (31.6% vs 42.6%, P = .012 and 27.2% vs 39.7%, P = .001, respectively).In real life, physicians may postpone to prescribe biological DMARDs and less frequently choose TNFi biological drugs in patients with multimorbidity. Furthermore, comorbidity may have a negative effect on the treatment response.
30177807 Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint 2018 Dec Rheumatoid arthritis is a common chronic inflammatory disorder and a major cause of disability. Despite the progress made with recent clinical use of anti-cytokine biologics, the response rate of rheumatoid arthritis treatment remains unsatisfactory, owing largely to the complexity of cytokine interactions and the multiplicity of cytokine targets. Here, we show a nanoparticle-based broad-spectrum anti-inflammatory strategy for rheumatoid arthritis management. By fusing neutrophil membrane onto polymeric cores, we prepare neutrophil membrane-coated nanoparticles that inherit the antigenic exterior and associated membrane functions of the source cells, which makes them ideal decoys of neutrophil-targeted biological molecules. It is shown that these nanoparticles can neutralize proinflammatory cytokines, suppress synovial inflammation, target deep into the cartilage matrix, and provide strong chondroprotection against joint damage. In a mouse model of collagen-induced arthritis and a human transgenic mouse model of arthritis, the neutrophil membrane-coated nanoparticles show significant therapeutic efficacy by ameliorating joint damage and suppressing overall arthritis severity.
29372595 Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis: a populat 2018 Aug AIM: To investigate the effects of hydroxychloroquine, sulfasalazine and methotrexate on ischemic stroke in patients with rheumatoid arthritis (RA). METHODS: This population-based retrospective cohort study included 7904 RA patients and 15 808 non-RA patients between 2000 and 2010. All of the participants were sampled from the National Health Insurance Research Database (NHIRD) of Taiwan. Using univariate analyses, these two groups of patients were compared to evaluate the differences in disease-modifying anti-rheumatic drugs usage and demographic variables. Cox proportional hazard models and Schoenfeld residuals test were performed to estimate the hazard ratios for ischemic stroke and proportional hazard assumptions of these drugs, respectively. RESULTS: The mean age of participants was about 53 years old, and about 70% of RA patients were women. The hazard ratio for ischemic stroke was 1.21 (95% CI: 1.10-1.34; P < 0.01) in the case group compared with the control group, and this significant difference persisted throughout the 10-year period. With respect to RA patients, while hydroxychloroquine showed an insignificant protective effect on ischemic stroke, sulfasalazine and methotrexate were found out to have inconsistent effects during these 10 years. The proportional hazard assumption test of methotrexate at > 0.5 defined daily dose (8.75 mg/week) was violated at a significant level after adjustment (P = 0.0002). CONCLUSIONS: At a dosage of > 0.5 defined daily dose, short-term methotrexate might decrease ischemic stroke risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.
29858238 Lack of Association among Peptidyl Arginine Deiminase Type 4 Autoantibodies, PADI4 Polymor 2018 Aug OBJECTIVE: We aimed to jointly investigate the role of antipeptidyl arginine deiminase type 4 antibodies (anti-PAD4) and polymorphisms in the PADI4 gene together with clinical variables in rheumatoid arthritis (RA). METHODS: Serum IgG autoantibodies to human recombinant PAD4 were identified by DELFIA technique in 745 patients with RA (366 available from previous studies). Genotyping of PADI4 was performed using TaqMan assays in 945 patients and 1118 controls. Clinical data, anticitrullinated protein antibodies (ACPA) status, shared epitope status, and a combined genetic risk score were also available. RESULTS: Anti-PAD4 antibodies were detected in 193 (26%) of 745 patients with RA; 149 (77%) of these were also ACPA-positive. No association was observed between anti-PAD4 status and clinical characteristics, PADI4 polymorphisms, or genetic risk scores after stratification for ACPA status. CONCLUSION: Taken together, the results from these combined serological, genetic, and clinical analyses suggest that anti-PAD4 appears to be a bystander autoantibody with no current clinical utility in RA.
29858113 Effect of treat-to-target strategies on bone erosion progression in early rheumatoid arthr 2018 Dec OBJECTIVES: To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI ≤ 3.3) compared to DAS28 remission (DAS28 < 2.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI ≤ 3.3 and group 2 (n = 43) aimed at DAS28-CRP < 2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months. RESULTS: After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor >16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair. CONCLUSIONS: Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair.
30168277 Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control s 2019 Jan Rheumatoid arthritis (RA) is a chronic, inflammatory disease closely linked with atherosclerosis. Recommended cardiovascular disease (CVD) integral evaluation includes screening for asymptomatic atherosclerosis plaques with carotid ultrasound (US). The aim of this study is to evaluate the carotid US characteristics, including carotid intima media thickness (cIMT) and carotid plaque (CP), and compare RA-patients and controls in a Mexican-mestizo population. METHOD: Prospective cross-sectional, observational study comparing RA-patients and matched controls without RA. Medical history and physical exam was performed in all subjects by a rheumatologist and two clinical blinded radiologists did the carotid US. Increased cIMT was defined as ≥0.9 mm. CP was defined as a focal narrowing ≥0.5 mm of the surrounding lumen or a cIMT ≥1.2 mm. Multivariable analysis was done comparing RA-patients and control subjects characteristics with carotid US. RESULT: In the final analysis 209 patients were included, 103 patients with RA and 106 controls. Bilateral CP was found more than twice in RA than controls (15.5% vs 6.6%). Unilateral CP was more common in either side evaluated, being heterogeneous plaques the most common in RA-patients. The prevalence of increased cIMT was found higher in RA-patients either in both sides (right 37.9% vs 15.1%, P = 0.00; left 43.7% vs 19.8%, P = 0.00) were statistically significant. CONCLUSION: It was confirmed that RA-patients have greater subclinical atherosclerosis represented in the carotid US measuring cIMT and CP as surrogates. RA-patients with subclinical atherosclerotic disease have more heterogeneous plaques characteristics.
29143933 Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified b 2018 Apr In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naïve patients and those with previous failures of biologic disease-modifying antirheumatic drugs (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or ≥ 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naïve patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with ≥ 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with ≥ 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with ≤ 2 bDMARD failures but significantly lower in those with ≥ 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.
29158166 The association between caspase-5 gene polymorphisms and rheumatoid arthritis in a Chinese 2018 Feb 5 Genetic factors are widely recognized to have a substantial effect on the susceptibility to rheumatoid arthritis (RA). We examined the contribution of caspase-5 (CASP5) gene polymorphisms to RA risk in a Chinese population. We conducted a case-control study involving 500 RA patients and 500 controls and performed co-expression analysis to identify genes associated with CASP5. We attempted to analyze the functions of these genes by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. We carried out genotyping using a custom-by-design 48-Plex SNP (single nucleotide polymorphism) Scanâ„¢ Kit. The independent effects of these genetic loci were evaluated by creating genetic risk scores (GRS). Bioinformatics analysis confirmed that CASP5 was related to the development of inflammation, which is the main feature of RA. In addition, the CASP5 rs9651713 polymorphism was associated with an increased risk of RA, but there was no significant association between any other tested polymorphism (rs2276414, rs2282657, rs3181171, rs3181318, rs3181175, rs3181337, and rs552217) and RA risk. In addition, a high GRS was positively correlated with the risk of RA. In conclusion, CASP5 may contribute to the development of RA by mediating inflammation. Larger studies with more diverse ethnic populations are needed to confirm these results.
30349197 miR-708-5p promotes fibroblast-like synoviocytes' cell apoptosis and ameliorates rheumatoi 2018 AIM: MicroRNAs (miRNA) are a class of small, highly conserved noncoding RNA molecules, which contain 18-28 nucleotides and are involved in the regulation of gene expression. It has been proved that microRNAs play a very important role in several key cellular processes, such as cell differentiation, cell cycle progression, and apoptosis, as well as in autoimmune disease. One recently identified miRNA, miR-708-5p, has been demonstrated to have profound roles in suppressing oncogenesis in different types of tumors. However, the role of miR-708-5p in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, in this study, we are aiming to identify the role of miR-708-5p in RA. METHODS: The expression level of miR-708-5p in synovial tissues of patients with RA is much lower than in non-RA controls. The effects of miR-708-5p on cell apoptosis, colony formation, and migration in fibroblast-like synoviocytes were assessed in MH7A cells. RESULTS: Results showed that delivery of miR-708-5p mimics into synovial fibroblasts MH7A could induce cell apoptosis and inhibit colony formation and migration. In addition, miR-708-5p mimics significantly inhibit Wnt3a/β-catenin pathway activity both in transcription and protein level, which could be reversed by the addition of R-spondin 1, an activator of Wnt pathway. R-spondin 1 could also reverse the inhibition of cell survival and proliferation, which was induced by miR-708-5p mimics in MH7A. Moreover, injection of miR-708-5p mimics into collagen-induced rat RA model could ameliorate the RA index and decrease Wnt3a/β-catenin expression in rat joint tissues. CONCLUSION: Therefore, we concluded that miR-708-5p is likely to be involved in RA pathogenesis via inhibition of Wnt3a/β-catenin pathway.
29314738 Long-term efficacy and safety of add-on tacrolimus for persistent, active rheumatoid arthr 2018 Mar AIM: To assess the long-term efficacy and safety of adding tacrolimus for patients with active rheumatoid arthritis (RA) despite anti-tumor necrosis factor (TNF) therapy with methotrexate. METHODS: Consecutive patients who were treated with adding tacrolimus onto anti-TNF therapy with methotrexate for active RA despite anti-TNF therapy with methotrexate, were retrospectively analyzed in terms of treatment response, achieving remission, subsequent treatment tapering and adverse events. RESULTS: Fifteen patients could be analyzed. Median symptom duration was 2.9 years and prior duration of anti-TNF therapy was 40 weeks. Median value of Disease Activity Score in 28 joints was 4.6. Five, eight and two were on infliximab, etanercept and adalimumab at the onset of tacrolimus, respectively. At 2 years, the proportions of patients achieving responses of American College of Rheumatology 50, 70 and 90, were 80%, 73% and 40%, respectively, and those achieving remission as defined by Simplified Disease Activity Index ≤ 3.3 were 67%. All patients could discontinue oral glucocorticoids and 10 had been successfully withdrawn from anti-TNF therapy for more than 1 year at the final observation. CONCLUSION: Adding tacrolimus onto anti-TNF therapy is a promising therapeutic option with sustained benefit for refractory RA patients despite treatment with anti-TNF therapy combined with methotrexate.
29740454 Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rhe 2018 Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are the most commonly used diagnostic markers of rheumatoid arthritis (RA). These antibodies are predominantly of the immunoglobulin (Ig) M (RF) or IgG (ACPA) isotype. Other subtypes of both antibodies-particularly IgA isotypes and other autoantibodies-such as RA33 antibodies-have been repeatedly reported but their diagnostic value has still not been fully elucidated. Here, we investigated the prevalence of IgA, IgG, and IgM subtypes of RF, ACPA, and RA33 antibodies in patients with RA. To determine the diagnostic specificity and sensitivity sera from 290 RA patients (165 early and 125 established disease), 261 disease controls and 100 healthy subjects were tested for the presence of IgA, IgG, and IgM isotypes of RF, ACPA, and RA33 by EliA™ platform (Phadia AB, Uppsala, Sweden). The most specific antibodies were IgG-ACPA, IgA-ACPA, and IgG-RF showing specificities >98%, closely followed by IgG- and IgA-RA33 while IgM subtypes were somewhat less specific, ranging from 95.8% (RA33) to 90% (RF). On the other hand, IgM-RF was the most sensitive subtype (65%) followed by IgG-ACPA (59.5%) and IgA-RF (50.7%). Other subtypes were less sensitive ranging from 35 (IgA-ACPA) to 6% (IgA-RA33). RA33 antibodies as well as IgA-RF and IgA-ACPA were found to increase the diagnostic sensitivity of serological testing since they were detected also in seronegative patients reducing their number from 109 to 85. Moreover, analyzing IgM-RF by EliA™ proved more sensitive than measuring RF by nephelometry and further reduced the number of seronegative patients to 76 individuals. Importantly, among antibody positive individuals, RA patients were found having significantly more antibodies (≥3) than disease controls which generally showed one or two antibody species. Thus, increasing the number of autoantibodies in serological routine testing provides valuable additional information allowing to better distinguish between RA and other rheumatic disorders, also in patients not showing antibodies in current routine diagnostics. In conclusion, testing for multiple autoantibody specificities increases the diagnostic power of autoimmune diagnostics and could further support physicians in clinical decision-making.
29452240 The effect of non-TNF-targeted biologics and small molecules on insulin resistance in infl 2018 Apr Inflammatory arthritides are chronic diseases characterised by an increase in cardiovascular risk, largely attributable to the synergy between high-grade systemic inflammation and an elevated prevalence of traditional cardiovascular risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D) play a key position. Previous studies demonstrated a potential insulin-sensitizing effect of anti-TNF biologic medications. For converse, less is known about the role of newer biologics or small molecules. For this reason, we performed a systematic review of the literature in order to identify the available data on the effect on insulin resistance of non-TNF targeting biologics and small molecules approved for the treatment of inflammatory arthritides. The search strategy initially retrieved 486 records of which only 10 articles were selected for inclusion in the final review. According to the available evidence, some of the newest molecules, in particular tocilizumab and abatacept, may have a role in improving insulin sensitivity; for converse, anakinra-mediated effect on glucose metabolism may exploit different facets of T2D pathophysiology, such as the preservation of beta-cell function. However, the data available on this issue are largely inconsistent and future, adequately designed studies are still needed to clarify the differential impact of novel therapeutics on individual pathophysiological features of T2D and other emerging cardiovascular risk factors.
30536918 Biological links in periodontitis and rheumatoid arthritis: Discovery via text-mining PubM 2019 Aug BACKGROUND AND OBJECTIVE: Primary research concerning molecular pathways that link rheumatoid arthritis with periodontitis is limited. Biomedical literature data mining can offer insights into putative linkage mechanisms toward hypothesis development, based on information discovery. The aim of this study was to explore potential Periodontitis-Rheumatoid Arthritis biological links by analysing "overlapping" genes reported in biomedical abstracts. MATERIAL AND METHODS: PubMed abstracts for terms: (a) "Periodontitis" or "Periodontal Diseases" (PD), (b) "Rheumatoid arthritis" (RA), and (c) their combination with "AND" (RA+PD), were each text-mined to extract genes using "Human Genome Nomenclature Committee" (HGNC) symbols. A gene-set common to RA and PD abstracts was determined (RA∩PD). Gene ontology (GO) profiles of RA∩PD and RA+PD were compared using "GoProfiler." Minimum order protein-protein interaction (PPI) and gene-miRNA networks of "differential genes" between RA∩PD and RA+PD were constructed with "networkAnalyst." RESULTS: Among 1676 genes documented in RA (10 5241 abstracts), and 893 genes in PD (80 982 abstracts), 535 genes were common (RA∩PD), from which 35 genes were also documented in RA+PD (415 abstracts). 41 GO-terms significantly different between RA∩PD and RA+PD GO profiles represented 38 biological processes including; nitric oxide metabolism, immunoglobulin production, hormonal regulation, catabolic process down-regulation, and leukocyte proliferation. The 500 differential genes' PPI and gene-miRNA networks showed REL, TRAF2, AQP1 genes, and miRNAs 335-5p, 17-5p, 93-5p with genes HMOX1 and SP1 as hub nodes. CONCLUSIONS: Text-mining biomedical abstracts revealed potentially shared but un-investigated links between PD and RA, meriting further research.
29777367 Effects of crocin on inflammatory activities in human fibroblast-like synoviocytes and col 2018 Jun Rheumatoid arthritis (RA) is a systemic autoimmune disease, characterized by the irreversible joint destruction resulted from the attack of inflammatory cells to the joints. Recent studies demonstrated that crocin is able to alleviate arthritis and suppress inflammatory responses, implying crocin as a potential promising antiarthritic agent. In this study, we confirmed the effect of crocin on RA and revealed its underlying mechanism by measuring lipopolysaccharides (LPS)-stimulated cytokine production in presence or absence of crocin. The effect of crocin was also tested in vivo using a mouse model of collagen-induced arthritis (CIA). It was found that crocin significantly repressed the LPS-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in human fibroblast-like synoviocytes (FLS). We tested the effect of crocin on nuclear factor-kappa B (NF-κB) signaling and observed that cells pre-treated with 500 μM of crocin exhibited lower levels of LPS-induced p-IκBα, p-IκB kinase (IKK) α/β, and p65 expression than those of untreated cells. In addition, we found when cells were stimulated with IKKβ, crocin pre-treatment showed significantly inhibitory effect on the luciferase activity of IL-1β. In vivo results also showed that crocin treatment dramatically reduced plasma levels of TNF-α, IL-1β, and IL-6 in CIA mice. Crocin is efficient to suppress the productions of TNF-α, IL-6, and IL-1β by blocking NF-κB signal activation through its interaction with IKK, suggesting that crocin could be an efficient treatment for RA.
30148440 Risk of hospitalisation for serious bacterial infections in patients with rheumatoid arthr 2019 Jan OBJECTIVES: The aims of this study were to define the risk of serious bacterial infections in patients receiving specific biological disease-modifying anti-rheumatic drugs (bDMARDs) and evaluating the effect of concomitant synthetic DMARDs (sDMARDs) in a large population-based sample of rheumatoid arthritis (RA) deriving from an administrative health database. METHODS: Data were extracted from health databases of Lombardy Region, Italy (2004-2013), as a part of the RECord-linkage On Rheumatic Diseases (RECORD) study. Patients with RA treated with approved bDMARDs were included. Hospitalisations for bacterial infections were evaluated by hospital discharge forms. The association between drug exposure and infections was assessed by survival models, with time-dependent covariates. Results are presented as hazard ratios (HR) and 95%CI, crude and adjusted for pre-specified confounders (sex, age, disease duration, Charlson Comorbidity Index, previous biologics, previous infections, use of methotrexate, leflunomide, corticosteroids, non-steroidal anti-inflammatory drugs). RESULTS: 4,656 RA patients with at least one bDMARD prescription were included, for a total of 7,601 biological courses; 3,603 (77.4%) women with a mean (SD) age of 55.8 (12.7) years. Crude incidence rate of hospitalised infection ranged from 0.14 to 2.95 per 1000 person-years. After multivariable adjustment, abatacept users (HR 0.29, 95%CI 0.10-0.82) had significantly lower risk of infections compared to etanercept. Concurrent treatment with methotrexate (0.72, 0.52-0.99) reduced the overall risk of infection while glucocorticoids increased it (1.09 per mg/day, 1.06-1.11). CONCLUSIONS: In RA patients treated with bDMARDs, abatacept was associated with the lowest risk of infections; overall risk was mitigated by concomitant methotrexate and increased by glucocorticoids in a dose-dependent manner.
30374749 Acceptable quality of life and low disease activity achievable among transition phase pati 2019 Mar OBJECTIVES: Across diagnosis groups, transition of adolescents and young adults from children's hospitals to adult care associates with decreased treatment adherence and suboptimal treatment results. Our aim was to compare the health-related quality of life (HRQoL) and disease activity of juvenile idiopathic arthritis (JIA) patients after the transfer of care to the adult clinic and adult patients in the same outpatient clinic. METHODS: All consecutive JIA patients aged 16 to 20 years who visited the transition clinic between September 2016 and August 2017 and all consecutive adult onset arthritis patients between December 2016 and August 2017 in the rheumatology outpatient clinic of Helsinki University Hospital were evaluated. HRQoL was measured by a generic instrument, 15D. RESULTS: A total of 291 patients, 130 JIA, and 161 adults were identified with respective median disease durations of 6.5 and 4.0 years. Adults had lower HRQoL measured by 15D (median 0.90 vs. 0.96, P < 0.001) and higher Disease Activity Score 28 (DAS28) than JIA patients (median 2.4 vs. 1.6, P < 0.001). Adults smoked more frequently than JIA patients (22% vs. 7%, P < 0.001). In multiple regression, female gender, smoking, disease activity, and obesity were associated with poorer HRQoL. Smoking adults had more active disease (DAS28 median 3.1 vs. 2.1, P = 0.031) and lower HRQoL (15D median 0.86 vs. 0.93, P < 0.001) than non-smoking adults. CONCLUSIONS: Transition phase JIA patients had acceptable HRQoL and lower disease activity than patients with adult onset rheumatic diseases with similar disease duration. Smoking was associated with more active disease and lower HRQoL.