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

ID PMID Title PublicationDate abstract
29738430 C19-Norditerpenoid Alkaloids from Aconitum szechenyianum. 2018 May 8 Three new C(19)-norditerpenoid alkaloids (1⁻3), along with two known C(19)-norditerpenoid alkaloids (4,5), have been isolated from Aconitum szechenyianum. Based on extensive spectroscopic techniques (1D, 2D-NMR, IR, and MS) and chemical methods, their structures were established as szechenyianine D (1), szechenyianine E (2), szechenyianine F (3), 8-O-methyl-14-benzoylaconine (4), and spicatine A (5). The immunosuppressive effects of compounds 1⁻5 were studied using a ConA-induced or LPS-induced splenocyte proliferation model. In vitro tests showed that Compounds 2, 4, and 5 suppressed ConA-induced or LPS-induced splenocyte proliferation in a concentration-dependent manner. The CC(50)/IC(50) values of 2, 4, and 5 suggested that these compounds were potential immunosuppressive agents for the treatment of autoimmune diseases characterized by arthritis, such as rheumatoid arthritis.
30183607 Real-world experience with tofacitinib for the treatment of rheumatoid arthritis. 2019 May OBJECTIVES: Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA). Tofacitinib 5 mg, twice daily, is approved for treatment, with or without methotrexate, of moderate to severe active RA in adults not adequately responding to, or not tolerating one or more DMARDs. In this narrative review we aimed to provide an overview of the real-world evidence for tofacitinib in RA. METHODS: The literature was reviewed up to March 2018 for studies regarding the efficacy and safety of tofacitinib for the treatment of RA. The focus was mainly on real-world studies with implications for every day clinical practice. RESULTS: The efficacy and safety of tofacitinib have been comprehensively assessed in a wide programme of randomised controlled trials. Extensive observational research on tofacitinib in RA is also ongoing worldwide and a substantial body of post-marketing real-world data from clinical practice is becoming available. There was a degree of consistency across the real-world studies reviewed. Tofacitinib tends to be used as monotherapy more frequently than bDMARDS and appears to be effective without background methotrexate. The data show a manageable safety profile, with no new safety signals and a discontinuation rate from safety issues <10%. Patients initiating tofacitinib usually have longer disease duration and have been exposed to longer bDMARDs than patients initiating a bDMARD. CONCLUSIONS: Real-world data are a key component of the evidence supporting the effectiveness of this novel drug and are of interest to all stakeholders. Treatment persistence and adherence to tofacitinib are good overall and similar to those seen for bDMARDs.
29858239 Rheumatoid Arthritis and Risk of Sexual Dysfunction: A Systematic Review and Metaanalysis. 2018 Oct OBJECTIVE: It has been reported that there is an association between rheumatoid arthritis (RA) and increased susceptibility to sexual dysfunction (SD). This systematic review and metaanalysis aimed to investigate whether RA was a risk factor for SD. METHODS: MEDLINE (PubMed), EMBASE, and the Cochrane Library were systematically searched for all studies assessing sexual function in patients with RA. The association between RA and risk of SD was summarized using relative risk (RR) with 95% CI. RESULTS: Overall, 44,745 participants (mean age 43.2 yrs) were included from 7 studies (4 cross-sectional and 3 case-control studies). Of these, 6642 were patients with RA, with the mean disease duration from 5.7 years to 12.17 years. The methodological qualities of the included studies were judged as moderate to high. Synthesis of results demonstrated that RA was significantly associated with an increased risk of SD in females (RR 1.73, 95% CI 1.36-2.22, p < 0.001; heterogeneity: I(2) 60.3%, p = 0.028) as well as in males (RR 1.99, 95% CI 1.64-2.43, p < 0.001). The outcomes related to the Grading of Recommendations Assessment, Development, and Evaluation approach showed that the absolute effect of RA on SD was 10 more per 1000 (6-15 more); the overall quality of evidence was rated as low. CONCLUSION: Evidence from included studies indicates that patients with RA have a significantly increased risk of SD, which suggests that both patients and clinicians should be aware of the potential role of RA in the development of SD.
29231278 Are obesity and rheumatoid arthritis interrelated? 2018 Jan OBJECTIVES: In recent years, both the prevalence of obesity and the incidence of RA have been rising. Our aim was to assess the association between overweight or obesity and rheumatoid arthritis (RA). DESIGN: Patients who were diagnosed with RA were compared with population-based controls, matched for age and sex (by a ratio of 1:5). Body measurements and smoking status were collected from medical records. Body mass index was classified in WHO categories of underweight, normal, overweight and obese (<18.5, 18.5-<25, 25-<30, ≥30 kg/m(2) ). χ(2) and t-tests and logistic regression models were used to compare the study groups and to assess the association between obesity and RA. SETTING: A cross-sectional analysis performed utilizing the database of Clalit Health Services, the largest healthcare provider organisation in Israel. Data were collected from the beginning of computerised database usage (around year 2000) until 2015. PARTICIPANTS: CHS covers over 4.4 million enrollees, of which all RA patients and matched controls were selected. MAIN OUTCOME MEASURES: Proportion of obesity (BMI≥30.0 kg/m(2) ) among RA patients and controls. RESULTS: The study included 11 406 patients with RA and 54 701 controls. The proportion of obese subjects among RA patients was higher in comparison with controls, (33.4% vs 31.6%, respectively). In multivariate regression model, smoking and obesity were found to be associated with RA, whereas male gender was found as inversely related to RA. CONCLUSIONS: Our findings demonstrate that obesity is significantly associated with RA. This finding underlines the role that obesity plays in inflammation and autoimmune conditions.
30189769 Pregnancy outcomes in women with rheumatoid arthritis: a retrospective population-based co 2020 Feb Purpose: To assess if pregnancies in women with rheumatoid arthritis (RA) are at a higher risk for adverse maternal and neonatal outcomes.Materials and methods: A retrospective cohort study was carried out using the Healthcare Cost and Utilization Project - National Inpatient Sample (HCUP-NIS) from the USA. All births that took place from 2004 to 2013 were identified and women were classified as having RA or not on the basis of ICD-9 coding. Unconditional logistic regression was used to evaluate the adjusted effect of RA on maternal and neonatal outcomes.Results: Of the total 8,417,607 births in our cohort, 6068 were among women with RA for an overall prevalence of 72 per 100,000 births. There was a steady increase in reported RA in pregnancy from 47 to 100 per 100,000 over the 10-year study period. Compared with women without RA, women with RA were more likely to develop pre-eclampsia/eclampsia, gestational diabetes, to present with preterm premature rupture of membranes(PPROM), to experience placental abruption and placenta previa, and to deliver by caesarean section. Postpartum, RA-complicated pregnancies were associated with wound complications and thromboembolisms. Congenital anomalies, small for gestational age and preterm birth were more common in neonates of women with RA.Conclusion: RA in pregnancy is associated with a greater likelihood of adverse maternal and neonatal outcomes. Women with RA should be made aware of these risks and be followed as a high risk pregnancy.
29193869 CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in 2018 Mar OBJECTIVE: Rheumatoid arthritis (RA) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus (eQTL) analysis of confirmed genetic risk loci in CD4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation. METHODS: RNA and DNA were isolated from purified B and/or CD4+ T cells obtained from the peripheral blood of 344 patients with early arthritis. Genotyping and global gene expression measurements were carried out using Illumina BeadChip microarrays. Variants in linkage disequilibrium (LD) with non-HLA RA single-nucleotide polymorphisms (defined as r(2) ≥ 0.8) were analyzed, seeking evidence of cis- or trans-eQTLs according to whether the associated probes were or were not within 4 Mb of these LD blocks. RESULTS: Genes subject to cis-eQTL effects that were common to both CD4+ and B lymphocytes at RA risk loci were FADS1, FADS2, BLK, FCRL3, ORMDL3, PPIL3, and GSDMB. In contrast, those acting on METTL21B, JAZF1, IKZF3, and PADI4 were unique to CD4+ lymphocytes, with the latter candidate risk gene being identified for the first time in this cell subset. B lymphocyte-specific eQTLs for SYNGR1 and CD83 were also found. At the 8p23 BLK-FAM167A locus, adjacent genes were subject to eQTLs whose activity differed markedly between cell types; in particular, the FAM167A effect displayed striking B lymphocyte specificity. No trans-eQTLs approached experiment-wide significance, and linear modeling did not identify a significant influence of biologic covariates on cis-eQTL effect sizes. CONCLUSION: These findings further refine the understanding of candidate causal genes in RA pathogenesis, thus providing an important platform from which downstream functional studies, directed toward particular cell types, may be prioritized.
30304699 Serum miRNA-371b-5p and miRNA-5100 act as biomarkers for systemic lupus erythematosus. 2018 Nov MicroRNAs (miRNAs) play important roles in the pathogenesis of systemic lupus erythematosus (SLE). Here, we investigated the serum miRNAs expression profiles in the serum of SLE and healthy controls, and identified the potential serum biomarkers for SLE. We screened and identified the differentially expressed miRNAs such as miR-371b-5p, miR-5100, miR-146a-5p among active SLE, inactive SLE and healthy controls based on the miRNAs expression array. Furthermore, the results of RT-qPCR confirmed that miR-371b-5p and miR-5100 expression was different among active SLE, inactive SLE and healthy controls. Moreover, we performed in a large cohort which we validated that expression of miR-371b-5p and miR-5100 was increased significantly in the serum of SLE compared with healthy controls and rheumatoid arthritis (RA), and was also higher in active SLE than that in inactive SLE. In addition, we found the associations between the expression levels of miR-371b-5p and miR-5100 and these clinical parameters of SLE. These results suggested that miR-371b-5p and miR-5100 may act as serum biomarkers for SLE.
29550837 Previously reported placebo-response-associated variants do not predict patient outcomes i 2019 Feb In clinical trials, a placebo response refers to improvement in disease symptoms arising from the psychological effect of receiving a treatment rather than the actual treatment under investigation. Previous research has reported genomic variation associated with the likelihood of observing a placebo response, but these studies have been limited in scope and have not been validated. Here, we analyzed whole-genome sequencing data from 784 patients undergoing placebo treatment in Phase III Asthma or Rheumatoid Arthritis trials to assess the impact of previously reported variation on patient outcomes in the placebo arms and to identify novel variants associated with the placebo response. Contrary to expectations based on previous reports, we did not observe any statistically significant associations between genomic variants and placebo treatment outcome. Our findings suggest that the biological origin of the placebo response is complex and likely to be variable between disease areas.
30056523 How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoi 2018 Dec Low-dose methotrexate (ld-MTX) that is administered during rheumatoid arthritis (RA) treatment has hematological adverse effects such as pancytopenia, although rare. Although well-established and widely used for hematological adverse effects caused by high-dose MTX, leucovorin (folinic acid) treatment does not have an agreed-upon administration for ld-MTX-induced pancytopenia. Here, we aimed to figure out whether there was any difference in response time between the regimens with and without folinic acid prescribed to our patients who developed pancytopenia while on MTX therapy, and to identify risk factors for its development. Our cases were collectively assessed together with other rare cases available in the literature that were reported in a similar manner with an explicitly indicated response time, in days. Thereupon, we looked for any difference in response time between the regimens with and without folinic acid. In total, ten of our patients experienced pancytopenia while on ld-MTX treatment. Mean day on which hematological response was achieved was as follows: 7 days in one patient on folic acid monotherapy, 6 days in three patients on granulocyte-colony stimulating factor (G-CSF) monotherapy, 4.5 days in two patients on leucovorin monotherapy, and 4 days in the remaining three patients who were treated with G-CSF + folinic acid/leucovorin. When we collectively evaluated our patients and the patients with an explicitly stated response duration in the literature (15 patients) and compared regimens including folinic acid to those without folinic acid, duration until response/recovery from pancytopenia was significantly shorter in folinic acid group than that in the group without folinic acid (5.47 ± 2.9 days vs 10 ± 3.77 days, p = 0.002). Treatment modalities including folinic acid (leucovorin) either with or without G-CSF result in a shorter recovery/response time compared to other agents. Leucovorin should definitely be considered and applied in rescue therapy for ld-MTX-associated side effects.
29352854 Fc gamma receptor binding profile of anti-citrullinated protein antibodies in immune compl 2018 Mar OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA). Here, we studied binding of ACPA-IgG immune complexes (IC) to individual Fc gamma receptors (FcγR) to identify potential effector mechanisms by which ACPA could contribute to RA pathogenesis. METHODS: ACPA-IgG1 and control IgG1(IgG1 depleted of ACPA-IgG1) were isolated from plasma and synovial fluid (SF) of RA patients by affinity chromatography using CCP2 peptides. Subsequently, IC were generated using fluorescently labelled F(ab')2 fragments against the F(ab')2 region of IgG, or by using citrullinated fibrinogen. IC were incubated with FcγR-transfected CHO cell lines or neutrophils from healthy donors. FcγR binding of IC was analysed by flow cytometry in the presence or absence of specific blocking antibodies. RESULTS: ACPA-IgG1 IC predominantly bound to FcγRI and FcγRIIIA on FcγR-transfected CHO cell lines, while much lower binding was observed to FcγRIIA and FcγRIIB. ACPA-IgG1 IC showed reduced binding to FcγRIIIA compared to control IgG1 IC, in line with enhanced ACPA-IgG1 Fc core-fucosylation. Neutrophils activated in vitro to induce de novo expression of FcγRI showed binding of ACPA-IgG IC, and blocking studies revealed that almost 30% of ACPA-IgG IC binding to activated neutrophils was mediated by FcγRI. CONCLUSIONS: Our studies show that ACPA-IgG1 IC bind predominately to activating FcγRI and FcγRIIIA, and highlight FcγRI expressed by activated neutrophils as relevant receptor for these IC. As neutrophils isolated from SF exhibit an activated state and express FcγRI in the synovial compartment, this IC-binding could contribute to driving disease pathogenesis in RA.
30468518 Comparison of rheumatoid arthritis (RA) and osteoarthritis (OA) based on microarray profil 2019 Jan The purpose of the present study was to investigate the underlying molecular mechanism of osteoarthritis (OA) and rheumatoid arthritis (RA) based on microarray profiles. Three human joint fibroblast-like synoviocytes (FLSs) microarray profiles including 26 OA samples, 33 RA samples, and 20 healthy control (HC) samples were downloaded from the GEO database. Differentially expressed genes (DEGs) between OA and HC (DEGsOA) and RA and HC (DEGsRA) were identified. Co-expressed and specific genes were analysed between DEGsOA and DEGsRA. Gene ontology, KEGG pathway enrichment, PPI network, and GSEA were performed to predict the function of DEGs. Two hundred seventy-six and 410 differential genes in DEGsOA and DEGsRA were observed. One hundred fifty coexpressed genes and 126 OA-specific genes (SELE, SERPINE1, and NFKBIA were the key genes) between DEGsOA and DEGsRA were enriched in the tumour necrosis factor (TNF) signalling pathway. However, 260 RA-specific genes of which the key genes were CCR5, CCR7, CXCR4, CCL5, and CCR4 were enriched in chemokine signalling pathway. Therefore, FLSs might exert an inflammatory effect by regulating TNF signalling pathway, targeting SELE, SERPINE1, and NFKBIA during the process of OA. Although TNF signalling pathway was also involved in the synovitis of RA, chemokine signalling pathway played the key role in RA FLSs mediating cell migration, invasion, and release of chemotaxis. In addition, CCR5, CCR7, CXCR4, CCL5, and CCR4 might be hub genes in RA. The different biomarkers and pathways identified in OA and RA may provide references for further study. SIGNIFICANCE OF THE STUDY: This study revealed the similar and different mechanisms of FLSs and different biomarkers that might with important regulatory effects on RA and OA. In OA, FLSs played an inflammatory role through TNF signalling pathway, targeting SELE, SERPINE1, and NFKBIA. Although TNF signalling pathway was also involved in the synovitis of RA, chemokine signalling pathway was a crucial pathway in mediating FLSs migration, invasion, and release of chemotaxis. CCR5, CCR7, CXCR4, CCL5, and CCR4 might be keys genes in RA. We expect that our results will bring more comprehensively understanding between RA and OA for researchers.
29929166 Effect of magnetic nanoparticles size on rheumatoid arthritis targeting and photothermal t 2018 Oct 1 Nanoparticles based multifunctional system exhibits great potential in diagnosis and therapy of rheumatoid arthritis (RA). The size of nanoparticles plays an essential role in biodistribution and cellular uptake, in turn affects the drug delivery efficiency and therapeutic effect. To investigate the optimal size for RA targeting, Fe(3)O(4) nanoparticles with well-defined particle sizes (70-350 nm) and identical surface properties were developed as model nanoparticles. The synthesized Fe(3)O(4) nanoparticles exhibited excellent biocompatibility and showed higher temperature response under irradiation of near infrared light. Size-dependent internalization was observed when incubated with inflammatory cells. Compared with large ones, small nanoparticles were more readily be phagocytized, leading to higher cytotoxicity in vitro. However, the in vivo experiment in CIA mice demonstrated a quite different result that nanoparticles with size of 220 nm exerted better accessibility to inflamed joint and resulted in higher temperature and better therapeutic effect under laser irradiation. This study not only offered a novel method for RA therapy but also a guideline for RA targeted drug carrier design.
29416136 Proteinases and their receptors in inflammatory arthritis: an overview. 2018 Mar Proteinases are enzymes with established roles in physiological and pathological processes such as digestion and the homeostasis, destruction and repair of tissues. Over the past few years, the hormone-like properties of circulating proteinases have become increasingly appreciated. Some proteolytic enzymes trigger cell signalling via proteinase-activated receptors, a family of G protein-coupled receptors that have been implicated in inflammation and pain in inflammatory arthritis. Proteinases can also regulate ion flux owing to the cross-sensitization of transient receptor potential cation channel subfamily V members 1 and 4, which are associated with mechanosensing and pain. In this Review, the idea that proteinases have the potential to orchestrate inflammatory signals by interacting with receptors on cells within the synovial microenvironment of an inflamed joint is revisited in three arthritic diseases: osteoarthritis, spondyloarthritis and rheumatoid arthritis. Unanswered questions are highlighted and the therapeutic potential of modulating this proteinase-receptor axis for the management of disease in patients with these types of arthritis is also discussed.
29176449 Can Appropriate Systemic Treatment Help Protect the Cornea in Patients With Rheumatoid Art 2018 Feb PURPOSE: To correlate rheumatologic with ophthalmic and laboratory findings in patients with rheumatoid arthritis (RA) to identify what effect these have on development of ocular disease. METHODS: This is a cross-sectional study of 172 eyes of 86 patients with RA. Patients were examined by a group of rheumatologists. Sociodemographic, clinical, and laboratory data were collected. All patients underwent complete ophthalmologic examination including corneal topography and endothelial cell count. RESULTS: There was no significant correlation between RA-negative prognostic indicators (NPIs) and pathologic corneal findings. Patients using disease-modifying antirheumatic drugs (DMARDs) and antimalarial drugs had greater corneal volumes (mean difference 8.51 mm, 90% confidence interval [CI], 3.98-13.04, P = 0.004; and 2.24, 90% CI, 0.32-4.54, P = 0.048, respectively). Patients using azathioprine had lower endothelial cell counts compared with those using other drugs (mean difference 180 cells/mm, 90% CI, 69-291, P = 0.008). Patients using biologic DMARDs had better tear osmolarity values (between 280 and 300 mOsm/L) than patients not using them (mean difference 14.3 mOsm/L, P = 0.022). There was no correlation between NPIs of RA and positive keratoconus screening indices (Spearman correlation OD -0.013, P = 0.91; OS -0.033, P = 0.76). CONCLUSIONS: There was no clear correlation between RA-NPIs and pathologic corneal findings in our study. DMARDs treatment may help maintain corneal integrity in our patients and prevented collagenolytic manifestations of RA. Other medications such as azathioprine should be used carefully, as endothelial damage may potentially occur.
30374689 Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid 2019 Feb Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima-media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRS(IMT), GRS(CP) and GRS(CAD), comprising intima-media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRS(IMT). Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRS(IMT) among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.
29748156 TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway 2018 Mar 1 Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients' samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
29655777 Body composition evaluated by body mass index and bioelectrical impedance vector analysis 2018 Sep BACKGROUND: Rheumatoid arthritis (RA) is a complex inflammatory disease that modifies body composition. Although body mass index (BMI) is one of the clinical nutrition tools widely used to assess indirectly nutritional status, it is not able to identify these body alterations. Bioelectrical Vector Analysis (BIVA) is an alternative method to assess hydration and body cell mass of patients with wasting conditions. OBJECTIVE: To investigate the differences in nutrition status according to BMI groups (normal, overweight and obesity) and BIVA classification (cachectic and non-cachectic) in women with RA. METHODS: Women with confirmed diagnosis of RA were included from January 2015 to June 2016. Whole-body bioelectrical impedance was measured using a tetrapolar and mono-frequency equipment. Patients were classified according to BMI as: low body weight (n = 6, 2.7%), normal (n = 59, 26.3%), overweight (n = 88, 39.3%) and obese (n = 71, 31.7%), and each group was divided into BIVA groups (cachectic 51.8% and non-cachectic 48.2%). RESULTS: A total of 224 RA patients were included, with mean age 52.7 years and median disease duration of 12 years. Significant differences were found in weight, arm circumference, waist, hip, resistance/height, reactance/height and erythrocyte sedimentation rate among all BMI groups. However, serum albumin levels were significantly different between cachectic and non-cachectic patients independently of BMI. In all BMI categories, cachectic groups had lower reactance and phase angle than non-cachectic subjects. CONCLUSION: RA patients with normal or even high BMI have a significantly lower muscle component. Evaluation of body composition with BIVA in RA patients could be an option for cachexia detection.
29692777 Long Non-Coding RNA GAPLINC Promotes Tumor-Like Biologic Behaviors of Fibroblast-Like Syno 2018 Rapidly accumulating evidence has now suggested that the long non-coding RNAs (LncRNAs), a large and diverse class of non-coding transcribed RNA molecules with diverse functional roles and mechanisms, play a major role in the pathogenesis of many human inflammatory diseases. Although some LncRNAs are overexpressed in plasma, T cell, and synovial tissues of patients with rheumatoid arthritis (RA), there is a dearth of knowledge in what role these transcripts play in fibroblast-like synoviocytes (FLSs) of these patients. Here, our studies showed that GAPLINC, a newly identified functional LncRNA in oncology, displayed a greater degree of expression in FLSs from RA than in patients with traumatic injury. GAPLINC suppression in RA-FLS cells revealed significant alterations in cell proliferation, invasion, migration, and proinflammatory cytokines production. Additionally, we performed a preliminary bioinformatics analysis of GAPLINC gene sequence in order to find its target molecules, using miRanda, PITA, RNAhybrid algorithms, Kyoto encyclopedia of genes and genomes, and gene ontology analysis. Since the results predicted that some of microRNAs and mRNA may interact with GAPLINC, we simulated a gene co-action network model based on a competitive endogenous RNA theory. Further verification of this model demonstrated that silencing of GAPLINC increased miR-382-5p and miR-575 expression. The results of this study suggest that GAPLINC may function as a novel microRNAs sponging agent affecting the biological characteristics of RA-FLSs. Additionally, GAPLINC may also promote RA-FLS tumor-like behaviors in a miR-382-5p-dependent and miR-575-dependent manner. Based upon these findings, LncRNA GAPLINC may provide a novel valuable therapeutic target for RA patients.
29325766 Duration of treatment with bisphosphonates at the time of osteonecrosis of the jaw onset i 2018 Jun INTRODUCTION: Rheumatoid arthritis (RA) is a frequent and co-morbid condition. One of the main complications is induced osteoporosis. Treatments related to this complication significantly modify oral and implant management. Affected patients represent a population at intermediate risk of osteonecrosis of the jaw (ONJ). The objective was to search the literature for durations of treatment with bisphosphonates at the time of ONJ occurrence in patients with RA in order to obtain an average duration. MATERIALS AND METHODS: A bibliographic search in the PubMed/Medline database was carried out using the following equation "(osteonecrosis and jaw) and rheumatoid arthritis" with no time limitation. The primary study endpoint was the duration of treatment with bisphosphonates (BP) at the time of ONJ onset in patients with RA. RESULTS: Twelve articles accounting for 50 patients were included. Patients had had a median of 46.8 months of treatment with BP before ONJ occurred. Mean, minimum and maximum treatment times were 48.68, 6 and 120 months, respectively. The standard deviation was 27.77 months. DISCUSSION: The median treatment duration in our cohort of patients with RA was less than that reported for osteoporosis. We therefore, recommend that practitioners take additional precautions regarding oral surgery or implant procedures, particularly in patients with RA who have been treated with BP for more than 4 years.
29246891 Corneal perforation from peripheral ulcerative keratopathy in patients with rheumatoid art 2018 Sep BACKGROUND/AIMS: This study quantifies the threat to vision and the survival in patients presenting with peripheral ulcerative keratopathy (PUK) corneal perforation associated with rheumatoid arthritis (RA) in the UK. METHODS: New cases of corneal perforation from PUK in patients with RA were prospectively collected from the UK via the British Ophthalmological Surveillance Unit from July 2012 to June 2014. An initial questionnaire collected data on presentation and the first 2 weeks' management, and a follow-up questionnaire collected 1-year data on ocular morbidity and mortality. RESULTS: 30 eyes of 28 patients were identified over 2 years, estimating a UK incidence of 0.234/million/year. 20/27 (74%) were female, with a median age of 68 years (range 41-84). The most common initial management was cyanoacrylate glue with a bandage contact lens, oral steroids, topical and oral antibiotics, and lubricants. Long-term management included corneal grafting in 12/20 (60%) eyes of patients living at 1 year. The 1-year all-cause mortality was 6/25 (24%), which increased to 1/2 (50%) if both eyes had perforated. In the remaining patients alive at 1-year follow-up, there was a 13/20 (65%) poor visual outcome of less than or equal to counting fingers. 8/25 (40%) patients had bilateral PUK, with 2/25 (8%) having bilateral perforation. 5/19 (26%) patients alive at 1-year follow-up were eligible for sight impairment registration. CONCLUSION: This study highlights the serious ocular morbidity and high mortality associated with corneal perforation from PUK in patients with RA despite treatment. The mortality doubled if both eyes perforated, which should serve as a harbinger of impending serious medical problems.