Browse

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

ID PMID Title PublicationDate abstract
28791676 Wolf's post-herpetic isotopic response to tocilizumab for rheumatoid arthritis. 2018 May Immediate and delayed hypersensitivity reactions may occur after the first or many exposures to tocilizumab, and they have varying presentations. Here, we describe a Wolf's isotopic response that manifested in a patient as erythema on the same site of a previous healed herpes zoster infection. This phenomenon has rarely been reported in the literature.
28582403 Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind pl 2017 The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.
27143107 Efficacy of add-on tacrolimus on methotrexate to maintain clinical remission after redisco 2017 Jan OBJECTIVES: To describe the efficacy of adding tacrolimus to maintain remission in patients with rheumatoid arthritis (RA) on methotrexate after discontinuation of tumor necrosis factor inhibitor (TNFi) therapy. METHODS: Consecutive patients with RA, who resumed a TNFi to treat flares after initial TNFi-free remission and discontinued a TNFi again after achieving remission and adding tacrolimus were enrolled. The lengths of remission after discontinuation of TNFi without or with tacrolimus were analyzed. RESULTS: Thirteen TNFi-free periods in six patients, in which seven were without and six were with tacrolimus were analyzed. All were seropositive females with a median age of 46 years and symptom duration of 1.2 years at the onset of TNFi therapy. Two were treated with infliximab and four were with etanercept. The median dose of tacrolimus was 2 mg/day with trough level of 4.5 ng/ml. The length of time to flare after discontinuation of TNFi therapy with tacrolimus was significantly longer than those without tacrolimus (median 107 weeks [range 4-207] versus 13 weeks [2-36]). After adding tacrolimus, only one patient resumed TNFi therapy and three had no flare until final observation. CONCLUSIONS: Add-on tacrolimus was effective in maintaining TNFi-free remission in patients with RA who ever relapsed after TNFi-free remission.
27501914 Depression risk in patients with late-onset rheumatoid arthritis in Germany. 2017 Feb GOAL: The goal of this study was to determine the prevalence of depression and its risk factors in patients with late-onset rheumatoid arthritis (RA) treated in German primary care practices. METHODS: Longitudinal data from general practices (n=1072) throughout Germany were analyzed. Individuals initially diagnosed with RA (2009-2013) were identified, and 7301 patients were included and matched (1:1) to 7301 controls. The primary outcome measure was the initial diagnosis of depression within 5 years after the index date in patients with and without RA. Cox proportional hazards models were used to adjust for confounders. RESULTS: The mean age was 72.2 years (SD: 7.6 years). A total of 34.9 % of patients were men. Depression diagnoses were present in 22.0 % of the RA group and 14.3 % of the control group after a 5-year follow-up period (p < 0.001). In the multivariate regression model, RA was a strong risk factor for the development of depression (HR: 1.55, p < 0.001). There was significant interaction of RA and diagnosed inflammatory polyarthropathies (IP) (RA*IP interaction: p < 0.001). Furthermore, dementia, cancer, osteoporosis, hypertension, and diabetes were associated with a higher risk of developing depression (p values <0.001). CONCLUSION: The risk of depression is significantly higher in patients with late-onset RA than in patients without RA for subjects treated in primary care practices in Germany. RA patients should be screened routinely for depression in order to ensure improved treatment and management.
27733572 Neutrophil biomarkers predict response to therapy with tumor necrosis factor inhibitors in 2017 Mar Neutrophils are implicated in the pathology of rheumatoid arthritis (RA), but the mechanisms regulating their activation are largely unknown. RA is a heterogeneous disease, and whereas many patients show clinical improvement during TNF inhibitor (TNFi) therapy, a significant proportion fails to respond. In vitro activation of neutrophils with agents, including TNF, results in rapid and selective changes in gene expression, but how neutrophils contribute to TNF signaling in RA and whether TNFi sensitivity involves differential neutrophil responses are unknown. With the use of RNA sequencing (RNA-Seq), we analyzed blood neutrophils from 20 RA patients, pre-TNFi therapy, to identify biomarkers of response, measured by a decrease in disease activity score based on 28 joint count (DAS28), 12 wk post-therapy. Biomarkers were validated by quantitative PCR (qPCR) of blood neutrophils from 2 further independent cohorts of RA patients: 16 pre-TNFi and 16 predisease-modifying anti-rheumatic drugs (DMARDs). Twenty-three neutrophil transcripts predicted a 12-wk response to TNFi: 10 (IFN-regulated) genes predicting a European League against Rheumatism (EULAR) good response and 13 different genes [neutrophil granule protein (NGP) genes] predicting a nonresponse. Statistical analysis indicated a predictive sensitivity and specificity of each gene in the panel of >80%, with some 100% specific. A combination of 3 genes [cytidine monophosphate kinase 2 (CMPK2), IFN-induced protein with tetratricopeptide repeats 1B (IFIT1B), and RNASE3] had the greatest predictive power [area under the curve (AUC) 0.94]. No correlation was found for a response to DMARDs. We conclude that this panel of genes is selective for predicting a response to TNFi and is not a surrogate marker for disease improvement. We also show that in RA, there is great plasticity in neutrophil phenotype, with circulating cells expressing genes normally only expressed in more immature cells.
28275265 Beyond citrullination: other post-translational protein modifications in rheumatoid arthri 2017 Jun The presence of autoantibodies is one of the hallmarks of rheumatoid arthritis (RA). In the past few decades, rheumatoid factors (autoantibodies that recognize the Fc-tail of immunoglobulins) as well as anti-citrullinated protein antibodies (ACPAs) have been studied intensively. ACPAs recognize post-translationally modified proteins in which the amino acid arginine has been converted into a citrulline. More recently, other autoantibody systems recognizing post-translationally modified proteins have also gained attention, including autoantibodies recognizing fragmented immunoglobulin (anti-hinge antibodies), autoantibodies recognizing acetylated proteins and autoantibodies recognizing proteins that are modified by adducts formed under oxidative stress. In particular, detailed insights have been obtained on the presence and properties of autoantibodies recognizing carbamylated proteins, commonly called anti-carbamylated protein (anti-CarP) antibodies. In this Review, we summarize the current knowledge relating to these emerging autoantibodies that recognize post-translationally modified proteins identified in RA, with an emphasis on anti-CarP antibodies.
28017911 Apelin concentrations are associated with altered atherosclerotic plaque stability mediato 2017 Jan BACKGROUND AND AIMS: Apelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. METHODS: Apelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis. RESULTS: In all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7). CONCLUSIONS: Apelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.
28975568 Modeled Health Economic Impact of a Hypothetical Certolizumab Pegol Risk-Sharing Scheme fo 2017 Oct PURPOSE: To model the American College of Rheumatology (ACR) outcomes, cost-effectiveness, and budget impact of certolizumab pegol (CZP) (with and without a hypothetical risk-sharing scheme at treatment initiation for biologic-naïve patients) versus the current mix of reimbursed biologics for treatment of moderate-to-severe rheumatoid arthritis (RA) in Finland. METHODS: A probabilistic model with 12-week cycles and a societal approach was developed for the years 2015-2019, accounting for differences in ACR responses (meta-analysis), mortality, and persistence. The risk-sharing scheme included a treatment switch and refund of the costs associated with CZP acquisition if patients failed to achieve ACR20 response at week 12. For the current treatment mix, ACR20 at week 24 determined treatment continuation. Quality-adjusted life years were derived on the basis of the Health Utilities Index. RESULTS: In the Finnish target population, CZP treatment with a risk-sharing scheme led to a estimated annual net expenditure decrease ranging from 1.7% in 2015 to 5.6% in 2019 compared with the current treatment mix. Per patient over the 5 years, CZP risk sharing was estimated to decrease the time without ACR response by 5%-units, decrease work absenteeism by 24 days, and increase the time with ACR20, ACR50, and ACR70 responses by 5%-, 6%-, and 1%-units, respectively, with a gain of 0.03 quality-adjusted life years. The modeled risk-sharing scheme showed reduced costs of €7866 per patient, with a more than 95% probability of cost-effectiveness when compared with the current treatment mix. CONCLUSION: The present analysis estimated that CZP, with or without the risk-sharing scheme, is a cost-effective alternative treatment for RA patients in Finland. The surplus provided by the CZP risk-sharing scheme could fund treatment for 6% more Finnish RA patients. FUNDING: UCB Pharma.
28807007 TNF-α-induced miR-155 regulates IL-6 signaling in rheumatoid synovial fibroblasts. 2017 Aug 14 BACKGROUND: MicroRNAs (miRNAs) are important regulators of a variety of inflammatory mediators. The present study was undertaken to elucidate the role of miRNAs in the rheumatoid cytokine network. METHODS: We analyzed miRNA expression in rheumatoid synovial fibroblasts (RASFs). miRNA array-based screening was used to identify miRNAs differentially expressed between tumor necrosis factor-α (TNF-α)-activated RASFs and untreated RASFs. Transfection of RASFs with miR-155 was used to analyze the function of miR-155. Real-time polymerase chain reaction (PCR) was used to measure the levels of miR-155 in RASFs. RESULTS: miRNA microarray analysis revealed that miR-155-5p was the most highly induced miRNA in TNF-α-stimulated RASFs. TNF-α-induced miR-155 expression in RASFs was time-dependent and TNFα dose-dependent, whereas, IL-6 stimulation did not affect miR-155 expression in RASFs. Transfection of miR-155 mimics into RASFs resulted in the decrease JAK2/STAT3 phosphorylation in IL-6-treated RASFs. CONCLUSIONS: The current results demonstrate that TNF-α modulated miRNA expressions in RASFs. Our data showed that miR-155, which is highly induced by TNF-α stimulation, inhibits IL-6-mediated JAK2/STAT3 activation in RASFs. These findings suggest that miR-155 contributes to the cross-regulation between TNF-α and IL-6-mediated inflammatory pathways in RA.
28857474 Association between serum vitamin D levels and neuropathic pain in rheumatoid arthritis pa 2018 Feb AIM: Recent literature suggests that neuropathic pain (NP) and vitamin D deficiency can occur concurrently in patients with rheumatoid arthritis (RA). This study aimed to examine the development of NP in patients with RA and the relationship between NP and vitamin D. METHODS: We used the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire to evaluate NP in 93 patients with RA. Demographic and clinical data were obtained from patient files and interviews, and patients' serum vitamin D levels were recorded. Patients were requested to complete both the Short Form-36 survey and the Health Assessment Questionnaire. RESULTS: Seventy-five of the eligible patients were female (80.6%), and 31 (33.3%) were diagnosed with NP according to the LANSS. There was a negative correlation between vitamin D levels and the LANSS score (P = 0.001). The prevalence of NP was 5.8 times higher among patients with serum vitamin D levels below 20 ng/mL than in patients with vitamin D levels ≥ 30 ng/mL. Based on the area under curve (AUC) values, we found that serum levels of vitamin D were a good predictor of NP diagnoses in patients with RA (AUC = 0.71). CONCLUSION: We found that vitamin D deficiency was asssociated with increased NP in patients with RA. Although further research is needed to clarify the association between serum vitamin D levels and NP, our study raises awareness of the need to screen for vitamin D deficiency in RA patients with NP.
28771010 Systems Pharmacology Dissection of Multiscale Mechanisms of Action for Herbal Medicines in 2017 Sep 5 As a chronic inflammatory and angiogenic disease with increased morbidity and mortality, rheumatoid arthritis (RA) is characterized by the proliferation of synovial tissue and the accumulation of excessive mononuclear infiltration, which always results in the joint deformity, disability, and eventually the destruction of the bone and cartilage. Traditional Chinese Medicine (TCM), with rich history of proper effectiveness in treating the inflammatory joint disease containing RA, has long combated such illness from, actually, an integrative and holistic point of view. However, its "multi-components" and "multi-targets" features make it very difficult to decipher the molecular mechanisms of RA from a systematic perspective if employing only routine methods. Presently, an innovative systems-pharmacology approach was introduced, which combined the ADME screening model, drug targeting, and network pharmacology, to explore the action mechanisms of botanic herbs for the treatment of RA. As a result, we uncovered 117 active compounds and 85 key molecular targets from seven RA-related herbs, which are mainly implicated in four signaling pathways, that is, vascular endothelial growth factor, PI3K-Akt, Toll-like receptor, and T-cell-receptor pathways. Additionally, the network relationships among the active components, target proteins, and pathways were further built to uncover the pharmacological characters of these herbs. Besides, molecular dynamics (MD) simulations and molecular mechanics-Poisson-Boltzmann surface area calculations were carried out to explore the binding interactions between the compounds and their receptors as well as to investigate the binding affinity of the ligand to their protein targets. In vitro experiments by ligand binding assays validate the reliability of the drug-target interactions as well as the MD results. The high binding affinities and good inhibitions of the active compounds indicate that the potential therapeutic effects of these herbal medicines for treating RA are exerted probably through the modulation of these relevant proteins, which further validates the rationality and reliability of the drug-target interactions as well as our the network-based analytical methods. This work may be of help for not only understanding the action mechanisms of TCM and for discovering new drugs from plants for the treatment of RA, but also providing a novel potential method for modern medicine in treating complex diseases.
27909081 Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthr 2017 Feb OBJECTIVE: To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798). METHODS: Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy. RESULTS: Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported. CONCLUSION: Longterm monotherapy with TCZ demonstrated continuing efficacy and safety.
28583713 IGF-1R signalling contributes to IL-6 production and T cell dependent inflammation in rheu 2017 Sep BACKGROUND: Signalling through insulin-like growth factor 1 receptor (IGF-1R) is essential for cell survival, but may turn pathogenic in uncontrolled tissue growth in tumours. In rheumatoid arthritis (RA), the IGF-1R signalling is activated and supports expansion of the inflamed synovia. AIM: In the present study, we assess if disruption of IGF-1R signalling resolves arthritis. MATERIAL AND METHODS: Clinical associations of IGF-1R expression in leukocytes of the peripheral blood were studied in 84 RA patients. Consequences of the IGF-1R signalling inhibition for arthritis were studied in mBSA immunised Balb/c mice treated with NT157 compound promoting degradation of insulin receptor substrates. RESULTS: In RA patients, high expression of IGF-1R in leukocytes was associated with systemic inflammation as verified by higher expression of NF-kB, serum levels of IL6 and erythrocyte sedimentation rate, and higher pain perception. Additionally, phosphorylated IGF-1R and STAT3 enriched T cells infiltrate in RA synovia. Treatment with NT157 inhibited the phosphorylation of IGF-1R and STAT3 in synovia, and alleviated arthritis and joint damage in mice. It also reduced expression of IGF-1R and despaired ERK and Akt signalling in spleen T cells. This limited IL-6 production, changed RoRgt/FoxP3 balance and IL17 levels. CONCLUSION: IGF-1R signalling contributes to T cell dependent inflammation in arthritis. Inhibition of IGF-1R on the level of insulin receptor substrates alleviates arthritis by restricting IL6-dependent formation of Th17 cells and may open for new treatment strategies in RA.
28935500 Mold metabolites drive rheumatoid arthritis in mice via promotion of IFN-gamma- and IL-17- 2017 Nov Environmental factors have been discussed as triggers for autoimmune diseases like rheumatoid arthritis (RA). However, the role of chemical exposures in activation or exacerbation of RA is not clarified yet. Exposure of DBA/1 mice to the mold metabolites ochratoxin A (OTA) or deoxynivalenol (DON) increased the prevalence and the clinical severity of RA compared to un-exposed mice using an experimental collagen-induced arthritis model. Mycotoxin-exposed mice showed enhanced serum IgG1 and IgG2a levels and an elevated production of IL-1β and IL-6 in inflamed joints and of IFN-γ and IL-17 in splenocytes. Additionally, OTA and DON increased the release of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in activated murine macrophages and supported the differentiation of naïve T cells into Th1 cells, while treatment of CD4+T cells with the supernatant from mycotoxin-exposed macrophages induced IL-17 production. Furthermore, exposure of mice to OTA or DON enhanced the gene expression of Stat1, Stat3 and Stat4 in the spleen while the collagen-induced increase of Socs1 and Socs3 was abolished. Our results demonstrate that mycotoxins increase the susceptibility to develop RA via an enhanced stimulation of macrophages and promotion of Th1/Th17 cell differentiation by induction of Stat signalling pathways and down-regulation of the Socs-mediated feedback inhibition.
27502891 Risk of lymphoma in patients exposed to antitumour necrosis factor therapy: results from t 2017 Mar OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of lymphoma compared with the general population. There are concerns that tumour necrosis factor inhibitors (TNFi) may exacerbate this risk. However, since the excess risk of lymphoma in RA is related to the cumulative burden of inflammation, TNFi may conversely reduce the risk of lymphoma by decreasing the burden of inflammation. The aim of this study was to compare the risk of lymphoma in subjects with RA treated with TNFi with those treated with non-biological therapy. METHODS: Subjects diagnosed by a rheumatologist with RA enrolled in the British Society for Rheumatology Rheumatoid Arthritis Register (BSRBR-RA), a prospective cohort study, were followed until first lymphoma, death or until 30 November 2013. Rates of lymphoma in the TNFi and non-biological-treated cohorts were compared using Cox regression. RESULTS: 11 931 TNFi-treated patients were compared with 3367 biological-naive patients. 84 lymphomas (88 (95% CI 70 to 109) per 100 000 person-years) were reported in the TNFi cohort and 30 lymphomas (154 (95% CI 104 to 220)) in the biological-naive cohort. After adjusting for differences in baseline characteristics, there was no difference in the risk of lymphoma for the TNFi versus the biological-naive group: HR 1.00 (95% CI 0.56 to 1.80). No risk differences were observed for individual TNFi. CONCLUSIONS: In medium-term follow-up, there is no evidence that tumour necrosis factor inhibition influences the risk of lymphoma over the background risk in subjects with RA.
28631046 Adherence of rheumatoid arthritis patients to biologic disease-modifying antirheumatic dru 2017 Oct The aims of this study were to evaluate adherence of rheumatoid arthritis (RA) patients to biological disease-modifying antirheumatic drugs (bDMARDs), identify potential risk factors, and analyze the discriminative ability of the Morisky-Green test (MGT) to detect bDMARD nonadherence. One hundred and seventy-eight adult RA patients treated with bDMARDs were included. Adherence was measured using the medication possession ratio (MPR) of the previous 6 months. An MPR >80% was considered good adherence. Patient demographics, clinical characteristics, and MGT scores were assessed through a standardized clinical interview at the cross-sectional date. One-hundred and twelve patients (63%) were taking subcutaneous bDMARDs, while 66 (37%) were taking intravenous drugs. One-hundred fifty-eight (88.8%) showed good adherence to bDMARDs, while 79 (61.2%) also correctly took concomitant conventional synthetic DMARDs (csDMARDs). In logistic regression models, nonadherence to bDMARDs was associated with higher disease activity [odds ratio (OR) 1.45; 95% CI, 1.03-2.03; p = 0.032] and subcutaneous route (OR 3.70; 95% CI 1.02-13.48; p = 0.040). MGT accurately identified an MPR >80% of bDMARDs in 76.9% of the patients. A sensitivity of 78%, specificity of 70%, positive predictive value of 95.3%, negative predictive value of 28.5%, positive likelihood ratio (LR) of 2.6, and negative LR of 0.3% were obtained. Adherence may be good for bDMARDs but is low for csDMARDs. Low adherence for bDMARDs is associated with poorer disease control during the past 6 months and use of subcutaneous route. These findings should alert doctors to consider possible low adherence before declaring treatment failure.
28147263 Subclinical atherosclerosis in Systemic Lupus Erythematosus: Comparable risk with Diabetes 2017 Mar OBJECTIVE: Although a high risk of subclinical atherosclerosis has been reported in Systemic Lupus Erythematosus (SLE), it is not adequately compared with that observed in other rheumatic and non-rheumatic high-cardiovascular (CVD) risk diseases, such as Rheumatoid Arthritis (RA) and Diabetes Mellitus (DM). Our objective was to evaluate the relative risk (RR) of subclinical atherosclerosis in SLE, RA and DM patients compared to healthy controls, and examine potential associations with traditional and disease-related CVD risk factors in SLE. METHODS: We examined for atherosclerotic plaques 460 individuals (92% female) without CVD history, using carotid and femoral artery ultrasound: 115 SLE patients and matched 1:1 for age and gender RA, DM, and control subjects. Multivariate models were used to determine relative risk estimates for the number of atherosclerotic plaques in patient groups versus controls, and associations of plaques with traditional CVD and disease-related factors in SLE. RESULTS: A nearly two-fold higher number of atherosclerotic plaques in the carotid and femoral arteries was detected in each of SLE, RA and DM groups compared to controls, after adjusting for the effect of traditional CVD risk factors (RR=1.80, 95% CI 1.05-3.08, p=0.033, RR=1.90 (1.11-3.26), p=0.019, RR=1.93 (1.14-3.28), p=0.015, respectively). In SLE patients, the number of atherosclerotic plaques was associated with age (p<0.001), smoking (p=0.016), hypertension (p=0.029), and cumulative corticosteroid dose (p=0.007). CONCLUSION: The relative risk of subclinical atherosclerosis in SLE was comparable to that found in RA and DM, indicating that SLE patients merit a similar diligence in CVD risk assessment and management measures.
28965939 Impaired intracellular pathogen clearance and inflammatory joint disease: Is Whipple's dis 2018 Oct Whipple's disease can mimic spondyloarthritis (SpA) or rheumatoid arthritis (RA) for many years and, in a few cases, induces the development of antibodies to cyclic citrullinated peptides. The causative agent Tropheryma whipplei can smolder within cells, including macrophages, by suppressing the xenophagic process, a type of selective autophagy that targets pathogens. Other inflammatory joint diseases may also stem from impaired xenophagy with persistence of bacteria or viruses that can eventually migrate from the mucous membranes to the joints and entheses, where they may exert adverse effects on immune responses, even if they fail to replicate. Xenophagy interferes with the loading of peptides (including self-peptides) onto major histocompatibility complex proteins. Another effect of xenophagy is the induction of citrullination, which accelerates pathogen clearance but can also contribute to loss of self-tolerance. Pathogens react to citrullination by becoming dormant. These facts suggest a role in SpA and RA for impaired xenophagy with migration of pathogens to joints and entheses, where they may remain dormant. Studies of fibroblast-like synoviocytes showed alterations in autophagy that correlated with citrullination of vimentin, alpha-enolase, and filaggrin, which are targets of RA-specific autoantibodies. Compared to autoimmune responses (T-cell or B-cell clones, autoantibodies) alone, metastatic spread of pathogens initially located in the mucous membranes as the event inducing inflammatory joint disease would constitute a better explanation to the heterogeneous distribution of the joint involvement, palindromic onset in some cases (as seen in Whipple's disease), occurrence of flares, and possible development of escape phenomenon to immunomodulating drugs in a manner reminiscent of delayed antibiotic resistance.
28201972 Cell-based Tolerogenic Therapy, Experience from Animal Models of Multiple Sclerosis, Type 2017 Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans. Also, perspectives for further improvement of tolerogenic cell preparation towards enhanced suppressive activity and stability of the cells will be discussed.
28608150 [Arthroscopy of the proximal interphalangeal joint]. 2017 Aug OBJECTIVE: Pain reduction in the affected proximal interphalangeal joint (PIP joint) by synovectomy, loose body extraction, dorsal arthrolysis. INDICATIONS: Therapy-resistant synovitis in rheumatoid arthritis (RA), early stage primary and secondary degenerative arthritis, loose bodies, capsular contracture. CONTRAINDICATIONS: Established biomechanic changes in RA (boutonniere and swanneck deformity). Large dorsal synovial cysts. Advanced radiologic changes in degenerative arthritis. Joint instability. Fresh skin lesion near portals. SURGICAL TECHNIQUE: Vertical traction of the affected finger in a Chinese finger trap if arthroscopy of a metacarpophalangeal joint is also planned, otherwise the joint can be placed on a hand table. Fill joint with Ringer solution. A radial and ulnar dorsal portal is created at joint space level, between the lateral band of the extensor tendon and the collateral ligament. Diagnostic arthroscopy. With insufficient visibility, "blind" shaving in dorsal recess. Completion of synovectomy under vision; 1.9 mm arthroscope with 30° angle of vision; 2.0 mm shaver (aggressive cutter). Closure of portals. Soft padded dressing. POSTOPERATIVE MANAGEMENT: Immediate postoperative mobilization for full range of finger movement. RESULTS: From 2009-2011, 91% of the patients treated with arthroscopic PIP joint synovectomy interviewed by telephone about pain reduction and satisfaction with the operation. Half of the 22 patients had RA and the other half degenerative arthritis, each with 14 joints treated. In all, 9 RA patients (11 treated joints, 79%) and only 1 patient with degenerative arthritis (2 treated joints, 14%) were content. The procedure achieves good pain reduction and functional improvement of the hand in RA. It can however not be recommended for degenerative arthritis except in selected cases.