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ID PMID Title PublicationDate abstract
29328507 Genetics of immune-mediated inflammatory diseases. 2018 Jul Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation of the normal immune response, which leads to inflammation. Together, they account for a high disease burden in the population, given that they are usually chronic conditions with associated co-morbidities. Examples include systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes. Since the advent of genome-wide association studies, evidence of considerable genetic overlap in the loci predisposing to a wide range of IMIDs has emerged. Understanding the genetic risk and extent of genetic overlap between IMIDs may help to determine which genes control which aspects of the different diseases; it may identify potential novel therapeutic targets for a number of these conditions, and/or it may facilitate repurposing existing therapies developed originally for different conditions. The findings show that autoantibody-mediated autoimmune diseases cluster more closely with each other than autoantibody-negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and ankylosing spondylitis which, instead, form a seronegative genetic cluster. The genetic clustering largely mirrors the known response to existing biological therapies, but apparent anomalies in treatment response are discussed.
29540697 Kaempferol targeting on the fibroblast growth factor receptor 3-ribosomal S6 kinase 2 sign 2018 Mar 14 Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68(+) macrophages with high frequency, while pRSK2-expressing CD4(+) T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.
30406565 Autoantibody and metalloproteinase activity in early arthritis. 2019 Mar OBJECTIVES: The aim of the study was to evaluate the frequency of anti-mutated citrullinated vimentin antibodies (a-Sa), anti-citrullinated α-enolase peptide 1 antibodies (a-CEP-1), anti-filaggrin antibodies (AFAs), heterogeneous nuclear ribonucleoprotein compies/anti-RA33-antibodies (a-hnRNP/RA33), anti-carbamylated protein antibodies (a-CarP), and metalloproteinase (MMPs) activity in patients with early inflammatory arthritis (EIA). METHODS: Seventy-four patients with EIA: 51 diagnosed with RA (rheumatoid arthritis) and 23 with UA (undifferentiated arthritis), and 20 healthy volunteers were enrolled to the study. Inflammatory markers, rheumatoid factor (RF), and antibodies mentioned above were assessed in all patients. RESULTS: In the EIA group, we observed significantly higher concentration of a-CEP-1 (65.8 ± 111.6 RU/mL) than in controls (2.0 ± 0.0 RU/mL). In RF(+) RA patients, we observed higher concentration of a-Sa and a-CEP-1 than in other groups. A-Sa were positive in 69% of RF(+) RA, 37% of RF(-) RA, 26% of UA patients and in 10% of controls. A-CEP-1 were positive in 77% of RF(+) RA patients, in 56% of RF(-) RA patients, in 8.7% of UA patients, but they were negative in controls. In patients with RF(+) RA, positive a-CarP were present statistically significantly more often than in RF (-) RA patients. No statistically significant difference in frequency of a-hnRNP/RA33 and AFA between RF(+) RA, RF(-) RA, and UA was observed. CONCLUSIONS: Our results suggest that a-CEP-1 may help in differentiation between RF(-) RA and UA. a-CEP-1 and a-Sa may be useful while diagnosing EIA. a-CarP may be used in differentiation of RA RF(-) and UA. However, a follow-up study is needed to evaluate the prognostic value of analyzed antibodies.
29606988 Methylglyoxal: A Relevant Marker of Disease Activity in Patients with Rheumatoid Arthritis 2018 BACKGROUND: The contribution of methylglyoxal (MGO) and soluble receptor for advanced glycation end products (sRAGE) in the presence of rheumatoid arthritis (RA) is still unknown. We investigated whether serum MGO and sRAGE were related to the presence of disease activity in RA. METHODS: 80 patients with RA and 30 control subjects were included in a cross-sectional study. The severity of RA was assessed using the disease activity score for 28 joints (DAS28). Serum MGO and sRAGE were measured by ELISA. RESULTS: Serum MGO levels were significantly higher in patients with RA versus control subjects (P < 0.001) and were increased in RA patients with higher disease activity versus RA patients with moderate disease activity (P = 0.019). Serum sRAGE concentrations were significantly decreased in RA patients with higher disease activity versus RA patients with moderate disease activity and versus control subjects (P = 0.004; P = 0.002, resp.). A multiple logistic regression analysis demonstrated that MGO was independently associated with the presence of activity disease in RA (OR = 1.17, 95% CI: 1.02-1.31, P = 0.01). CONCLUSION: Serum MGO and sRAGE levels are inversely related to the activity of RA, and MGO is independently associated with a higher disease activity of RA.
30008151 Cell adhesion molecules and plasminogen activator inhibitor type-1 (PAI-1) in patients wit 2018 Nov Rheumatoid arthritis (RA) is a chronic inflammatory and systemic disease characterized by endothelial activation. The main objective of this study was to verify the profile of cell adhesion molecules (CAM) in RA patients, and the influence of metabolic syndrome (MetS) and drugs used in the treatment of RA in this profile. A second objective was to propose models of prediction of activity in RA using these biomarkers. A total of 115 healthy individuals and 144 RA patients were enrolled. Disease activity was determined by DAS28 (disease activity score 28) based on erythrocyte sedimentation rate (DAS28-ESR) or C-reactive protein (DAS28-CRP). Serum CAM and plasminogen activator inhibitor type-1 (PAI-1), anthropometric and immunological parameters were measured. Vascular cell adhesion molecule-1 (VCAM-1) was significantly decreased, and PAI-1 was significantly higher in RA patients as compared to controls. Binary logistic regression analysis showed that VCAM-1, CRP, and tumor necrosis factor-α (TNF-α) predicted RA with a sensitivity of 95.9% and a specificity of 89.5%. 42.9% of the variance in DAS28-ESR and 49.2% of the variance in DAS28-CRP are explained by increased PAI-1, TNF-α, body mass index (BMI) and decreased platelet endothelial cell adhesion molecule 1 (PECAM-1). Our data show that lower levels of VCAM-1 are associated with RA independently of MetS, while increased PAI-1 levels were associated with both RA and MetS and increased selectins (E-selectin and P-selectin) were exclusively associated with MetS and not with RA. A model to predict disease activity based on PECAM-1, PAI-1, TNF-α, age and BMI is proposed.
29465369 Altered gene expression profiles of histone lysine methyltransferases and demethylases in 2018 Mar OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs. RESULTS: The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs. CONCLUSIONS: The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.
29907885 Recognition and control of hypertension, diabetes, and dyslipidemia in patients with rheum 2018 Aug Absolute cardiovascular risk of an individual with rheumatoid arthritis (RA) is greater when compared to the general population, and several factors have proven to be important for the development of coronary artery disease (CAD) in these patients, including factors related to the underlying disease, such as the systemic inflammatory response, drugs used in its treatment, and a higher prevalence of traditional risk factors for CAD. Our aim is to describe the recognition and control frequencies of systemic arterial hypertension (SAH), dyslipidemia, and diabetes mellitus (DM) in RA patients. Patients with RA answered a questionnaire focused on their general knowledge of the risk factors for CAD, as well as on the recognition of the risk factors that they possess. The patient's information, collected from a structured medical record, was reviewed to evaluate the control of risk factors. Hundred and thirty-four patients were included in the study. One patient was excluded due to the impossibility of reviewing her medical records. Therefore, 133 patients remained in the study. Patients had a mean (SD) age of 57.3 (12.9) years. SAH was diagnosed in 88 subjects, with a recognition frequency of 89.8%, and 63.3% had desirable blood pressure control. Seventy-two patients were diagnosed with dyslipidemia; 68.1% recognized that they had dyslipidemia and 69.4% achieved desirable LDL-c control. Twenty-two patients had DM; 90.9% admitted being diabetic and 40.9% had desirable glycemic control. The frequencies of the CAD risk factor recognition and control were high in comparison to those described for the general population.
29748857 Dynamic of changes in coronary artery calcification in early rheumatoid arthritis patients 2018 Jul The coronary artery calcification (CAC) progression may be useful noninvasive predictor of future cardiovascular events (CVE). The progression rate of CAC in patients with early rheumatoid arthritis (RA) is poorly understood. To assess the dynamic of CAC scores in early RA patients for 18 months, 74 RA adult patients (ACR/EULAR criteria, 2010, duration ≤ 12 months, with moderate/high RA activity, without prior administration of disease-modifying anti-rheumatic drugs or glucocorticoids) were enrolled within the framework of the observational study: women 73%, median age 56 years, median RA duration 6 months, median DAS28[ESR] 5.4. Most of the patients had multiple Traditional Risk Factors (TRFs) of Cardiovascular Disease (CVD). All patients at baseline and after 18 months underwent 32-row scanning for CAC scoring. In patients younger than 45 years (n = 16) any CAC was not detected during 18 months. Among patients older than 45 years four new events of CAC were detected. Among patients older than 45 years with baseline CAC (n = 34) increase in CAC scores was detected in 82% cases. Among them, Δ Agatston Score exceeded the median annual Agatston Score progression predicted for the general population according to the Multi-Ethnic Study of Atherosclerosis (MESA) data in 57% of early RA patients. The significant increase of Agatston Score in accordance with Sevrukov's method was met in one patient with newly diagnosed CAC and among patients with baseline CAC-in 29%. The presence of CAC progression was associated with lower baseline total cholesterol (TC) level (p < 0.05). The extent of CAC progression associated with male gender and arterial hypertension (AH) (p < 0.05). Association between CAC dynamic and statin therapy, RA activity and cumulative inflammatory burden, response to anti-rheumatic therapy and the type of this therapy were not detected. Early RA patients older than 45 years have high incidence of CAC progression during 18 months. More than half of the early RA patients had the increase in AS which exceeded the median annual progression of Agatston Score in the MESA. The CAC progression was associated with male gender, AH and lower baseline TC level. We did not detect any association between CAC progression and statin therapy, RA activity and type of anti-rheumatic therapy.
30245282 The Effect of Puerarin on Carotid Intima-media Thickness in Patients With Active Rheumatoi 2018 Oct PURPOSE: Cardiovascular and diabetic complications are the main causes of death in patients with rheumatoid arthritis (RA). Puerarin has potential protective effects against subclinical atherosclerosis and insulin resistance, but the clinical evidence is still not sufficient to draw definitive conclusions. Therefore, we performed the clinical trial to assess the effect of puerarin on carotid intima-media thickness (CIMT) in RA. METHODS: This is an open, controlled, randomized, and parallel-group comparison study of 119 patients with a definite diagnose of active RA. All 119 consecutive patients with RA receiving routine antirheumatic care were randomized to receive treatment with (n = 60; 16 males and 44 females; mean age, 52.97 years; 95% CI, 49.78-56.15 years) or without (n = 59; 17 males and 42 females; mean age, 54.05 years; 95% CI, 50.03-58.07 years) 400mg of puerarin. The effects of both interventions on CIMT, homeostasis model assessment of insulin resistance (HOMA-IR) value, and possible adverse events were assessed and compared at entry, 12 weeks, and 24 weeks. The collected data were processed and assessed using ANCOVA, paired t test, repeated-measure ANOVA, one-way ANOVA, Pearson's χ(2) test, Fisher exact test, Kaplan-Meier survival analysis, Pearson correlation, and LOESS (locally weighted smoothing) regression analysis. FINDINGS: No significant adverse effects occurred concerning the use of puerarin, and both interventions were generally well tolerated in all the patients. A tiny but significant decrease of CIMT was observed in puerarin-treated patients at 24 weeks (-0.003 mm; 95% CI, -0.005 to -0.001vs 0.019 mm; 95% CI, -0.002 to 0.040; P < 0.001). At 24 weeks, insulin resistance was indicated with more pronounced improvement in the puerarin group versus the control group (homeostasis model assessment, -0.40; 95% CI, -0.47 to -0.33vs -0.05; 95% CI, -0.08 to -0.01; P < 0.001). Correlation analysis indicated an interaction between the parallel reductions in CIMT and insulin resistance in the puerarin group (r = 0.878, P < 0.001) but not in the control group. IMPLICATIONS: In the study, 24 weeks of treatment with 400mg of puerarin exerted a significant effect against CIMT progression in patients with active RA, which may be associated with the improvement of insulin resistance. Puerarin holds promise as a drug candidate for the prevention and treatment of cardiometabolic comorbidities in patients with active RA. However, more strictly designed trials, such as double-blind and placebo-controlled trials, are still required. ClinicalTrials.gov identifier: NCT02254655.
29895378 Effect of anti-rheumatic treatment on selenium levels in inflammatory arthritis. 2018 Sep OBJECTIVES: The reason for increased cardiovascular risk in inflammatory arthritis (IA) is unclear. Interestingly, selenium-deficiency is suspected to contribute to the development of cardiovascular disease (CVD) in the general population. Although the reference range of serum selenium (s-selenium) is 50-120 μg/L, there are indications that levels up to 85 μg/L might not be sufficient for optimal cardioprotection. Our aim was to examine s-selenium levels in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), to evaluate the effect of anti-rheumatic treatment on s-selenium levels, and to assess relationships between s-selenium levels and clinical and laboratory parameters including markers of disease activity and CVD risk. METHODS: We examined 64 patients with RA, 40 with PsA and 26 with AS starting with methotrexate (MTX) monotherapy or anti-tumor necrosis factor therapy (anti-TNF) with or without methotrexate (anti-TNF ± MTX) due to active disease. S-selenium, inflammatory biomarkers, endothelial function (EF) and other variables were examined at baseline and after 6 weeks and 6 months of treatment. RESULTS: In the total IA group, s-selenium increased within 6 weeks of anti-rheumatic treatment, and thereafter the levels remained stable until the end of the 6 months follow-up period. There were no significant differences in s-selenium changes between the three diagnostic groups and between the two treatment regimens. Changes in s-selenium were negatively related to changes in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), but there were no significant relationships to any other of the examined risk parameters for CVD including EF. CONCLUSION: IA patients had s-selenium within the reference range, but below the level that might be necessary for optimal CVD protection. Anti-rheumatic treatment had a relatively rapid and sustained effect on s-selenium levels. The increase in s-selenium was related to reduction in inflammatory activity. In theory, anti-rheumatic drugs might improve s-selenium levels through inhibition of pro-inflammatory processes or through other mechanisms. Although we have not revealed any significant relationships between s-selenium and CVD risk parameters, the role of suboptimal s-selenium levels in pathogenesis of premature CVD in IA cannot be ruled out.
30328021 Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthrit 2018 Dec This study aimed to explore whether interleukin-10 polymorphisms are associated with susceptibility to rheumatoid arthritis (RA). Studies that have analyzed the associations of the interleukin-10-1082G>A, -592C>A, and -819C>T polymorphisms with RA were searched for in PubMed and EMBASE. Sensitivity and cumulative analyses were conducted to measure the robustness of our findings. Egger's linear regression and Begg's funnel plots were performed to analyze publication bias. The source of heterogeneity was analyzed by subgroup analysis and meta-regression. This meta-analysis involved 2661 RA patients and 3249 controls in 16 studies. There were significant associations with RA in the AG vs AA model (OR = 0.79, 95% CI = 0.67-0.93, P < 0.01) and the AG + GG vs AA model (OR = 0.80, 95% CI = 0.69-0.93, P < 0.01) for the interleukin-10-1082G>A polymorphism, in the TC vs TT model (OR = 0.61, 95% CI = 0.44-0.84, P < 0.01) and the CC vs TT model (OR = 0.64, 95% CI = 0.46-0.89, P < 0.01) for the interleukin-10-819C>T polymorphism, and in the AC vs AA model (OR = 0.73, 95% CI = 0.56-0.96, P = 0.03) and the AC + CC vs AA model (OR = 0.68, 95% CI = 0.47-0.98, P = 0.04) for the interleukin-10-592C>A polymorphism. Meta-regression revealed that the genotyping method was a major cause of heterogeneity in the AC vs AA model and the AC + CC vs AA model for the interleukin-10-592C>A polymorphism. This meta-analysis showed the interleukin-10-1082G>A, -592C>A, and -819C>T polymorphisms are correlated with the susceptibility to RA. Meta-regression indicated that the genotyping method is a major driver of heterogeneity in the relationship between the interleukin-10-592C>A polymorphism and RA.
30008459 Primary and Secondary Fibromyalgia Are The Same: The Universality of Polysymptomatic Distr 2019 Feb OBJECTIVE: Polysymptomatic distress (PSD) is the underlying metric of fibromyalgia (FM), and levels of PSD can identify criteria-positive FM with > 90% accuracy. We used levels of the PSD scale to test whether symptom levels in primary FM (PFM) and secondary FM (SFM) were the same and whether symptoms were equivalent in persons not meeting FM criteria. METHODS: We studied 1525 patients with a clinical diagnosis of FM and 12,037 patients with rheumatoid arthritis (RA). We used regression models to compare patients with potential and actual PFM to RA patients with potential and actual SFM for 17 key clinical variables. RESULTS: When controlled for PSD values, the widespread pain index, symptom severity scale, and pain, global, quality of life, and physical and mental component scores were essentially the same or only slightly different in PFM and SFM. Health Assessment Questionnaire-Disability Index scores were slightly higher in SFM (0.21 units), as was the painful joint count (1.6 joints). Overall, higher PSD scores were associated with more severe symptoms or abnormal status. PSD scores in patients not satisfying FM criteria and in patients satisfying criteria operated similarly. CONCLUSION: PFM and SFM are equivalent regarding symptom burden. PSD scores are more informative about severity and severity within diagnosis than dichotomization into FM/non-FM. Studies of FM versus "healthy individuals," or FM versus other diseases, are inherently defective, while studies of FM and PSD in RA offer the opportunity to have meaningful comparison groups, because there are no readily available unbiased appropriate controls for PFM.
29982776 Autophagy induces protein carbamylation in fibroblast-like synoviocytes from patients with 2018 Nov 1 OBJECTIVES: Autophagy is a homeostatic and physiological process that promotes the turnover of proteins and organelles damaged in conditions of cellular stress. We previously demonstrated that autophagy represents a key processing event creating a substrate for autoreactivity, which is involved in post-translational changes and generation of citrullinated peptides, recognized by the immune system in RA. In this study, we analysed whether autophagy is involved in other post-translational changes that can generate autoantigens, focusing on carbamylation processes. Carbamylation is a nonenzymatic post-translational modification, in which homocitrulline is generated by the reaction of cyanate with the primary amine of lysine residues; carbamylated peptides may accumulate during inflammation conditions. METHODS: The role of autophagy in the generation of carbamylated proteins was evaluated in vitro in fibroblasts as well as in synoviocytes from RA patients, treated with 5 μM tunicamycin or 200 nM rapamycin; the correlation between autophagy and carbamylated proteins was analysed in mononuclear cells from 30 naïve early-active RA patients. RESULTS: Our results demonstrated that cells treated with tunicamycin or rapamycin showed a significant increase of carbamylated proteins. Immunoblotting and immunoprecipitation experiments identified vimentin as the main carbamylated protein. Furthermore, a correlation was found between autophagy and carbamylation levels in mononuclear cells of naïve RA patients. CONCLUSION: These data indicate that autophagy is able to induce in vitro carbamylation processes, and in vivo appears to be related to an increase in carbamylation during RA. These observations introduce a new pathogenetic mechanism of disease, which could contribute to more accurate monitoring of patients.
30140263 Smoking Is Associated With Low Levels of Soluble PD-L1 in Rheumatoid Arthritis. 2018 BACKGROUND: Smoking is a risk factor for developing rheumatoid arthritis (RA), but the mechanism remains uncertain. We previously demonstrated that smoking lowers the T cell activation threshold by limiting programmed death protein 1 (PD-1) expression. AIM: To investigate how smoking influence the levels of soluble PD-1 ligand (sPD-L1). METHOD: Serum levels of sPD-L1 were measured in 246 RA patients and in 168 healthy subjects. The analysis was done with respect to inflammation, smoking, treatments, and autoantibody status. The effect of therapeutic TNF-inhibiting antibodies (TNFi) on sPD-L1 was studied in 16 RA patients at their first infliximab infusion. The expression of Fcγ-receptor (FcγR) subclass IIB and IIIA was analyzed with quantitative polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) from 12 RA patients and 15 healthy controls, and in healthy PBMC exposed to IgG containing antibodies to cyclic citrullinated peptides (aCCP). RESULTS: The negative association between smoking and sPD-L1 in RA patients was established by multiple logistic regression (OR = 0.52, p = 0.038). Other covariates in the regression model were serum levels of IL-1β representing inflammation (OR = 1.6, p = 0.0076) and aCCP positivity (OR = 1.9, p = 0.047). First infliximab infusion repressed sPD-L1 (p = 0.023) in patients, and low levels of sPD-L1 were found in patients with early RA treated with TNFi (p = 0.018). Treatment with TNFi was associated with higher sPD-L1 in patients with long disease duration (p = 0.041) and restored levels in smokers. In vitro exposure to aCCP+ IgG suppressed sPD-L1 (p = 0.036), but aCCP+ patients with long disease duration had higher sPD-L1 (p = 0.016). High ratio of the inhibitory FcγR subclass IIB over the stimulatory IIIA resulted in low sPD-L1 release (p = 0.029). Smoking was associated with a higher FcγR IIB/IIIA ratio (p = 0.00062) and lower levels of sPD-L1 (p = 0.013). CONCLUSION: In RA, serum sPD-L1 was related to systemic inflammation and aCCP positivity. Smoking altered the expression of FcγRs and limited sPD-L1 in RA patients, permitting inappropriate T cell responses. Differential regulation of sPD-L1 during the early and late RA may indicate transposition from acute to chronic inflammation.
29047218 Risk of Incident Chronic Obstructive Pulmonary Disease in Rheumatoid Arthritis: A Populati 2019 May OBJECTIVE: Studies have demonstrated a link between chronic obstructive pulmonary disease (COPD) and inflammation, raising the question whether chronic inflammatory conditions, such as rheumatoid arthritis (RA), predispose to COPD. Our objective was to evaluate the risk of incident COPD hospitalization in RA compared to the general population. METHODS: We studied a population-based incident RA cohort with matched general population controls, using administrative health data. All incident RA cases in British Columbia who first met RA definition between January 1996 and December 2006 were selected using previously published criteria. General population controls were randomly selected, matched 1:1 to RA cases on birth year, sex, and index year. COPD outcome was defined as hospitalization with a primary COPD code. Incidence rates, 95% confidence intervals (95% CIs), and incidence rate ratios (IRRs) were calculated for RA and controls. Multivariable Cox proportional hazards models estimated the risk of COPD in RA compared to the general population after adjusting for potential confounders. Sensitivity analyses were performed to test the robustness of the results to the possible confounding effect of smoking, unavailable in administrative data, and to COPD outcome definitions. RESULTS: The cohorts included 24,625 RA individuals and 25,396 controls. The incidence of COPD hospitalization was greater in RA than controls (IRR 1.58, 95% CI 1.34-1.87). After adjusting for potential confounders, RA cases had a 47% greater risk of COPD hospitalization than controls. The increased risk remained significant after modeling for smoking and with varying COPD definitions. CONCLUSION: In our population-based cohort, individuals with RA had a 47% greater risk of COPD hospitalization compared to the general population.
30357484 Tocilizumab-induced psoriasis-like eruption resolved by shortening the dose interval in a 2019 Jan Tocilizumab (TCZ) is a humanized antihuman interleukin-6 (IL-6) receptor antibody used for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). While TCZ could act as a therapeutic agent, it has a potential for inducing adverse drug events including psoriasis-like eruption. Seven cases with specific reference to TCZ-induced psoriasis eruption have been reported worldwide so far. In these cases, treatments with the same dosage of TCZ were either maintained or discontinued. Herein, we report a case involving a 74-year-old man diagnosed with rheumatoid factor-positive and anti-citrullinated protein antibody-positive RA with comorbidity of atopic dermatitis. TCZ was administered intravenously with oral methotrexate. After the third infusion, the patient developed TCZ-induced psoriasis-like eruptions, which were resolved by shortening the dose interval. Eruption recurrence was not observed after frequent TCZ subcutaneous injection. Our case may help physicians manage TCZ-induced psoriasis-like eruption.
30245093 Predictors for progression of two different types of cervical lesions in rheumatoid arthri 2019 Mar BACKGROUND: Biologic agents (BAs) enabled not only a reduction of disease activity but also a slowing down of structural damage to the joints in patients with rheumatoid arthritis (RA). However, the incidence of cervical lesions in patients with RA is still high. PURPOSE: To elucidate the predictors for the progression of two different cervical lesions in patients with RA under BA treatment. METHODS: Of 151 subjects who received more than two years of continuous BA treatment, 101 subjects who had cervical X-ray images taken at baseline and final visit were enrolled. The mean disease duration and mean radiography interval were 10.6 years and 4.4 years, respectively. The existence and progression of cervical lesions (atlanto-axial subluxation [AAS], vertical subluxation [VS], and subaxial subluxation [SS]) were investigated. And predictors for the AAS or VS progression were analyzed by multivariate logistic regression analysis. RESULTS: The incidence of cervical lesions at baseline were no pre-existing cervical lesion (none) in 50 cases (50%), AAS only in 32 (32%), both AAS and VS in 12 (12%), and VS only in 7 cases (7%). In the none group, only 4 cases of AAS progression (8%) was observed during the follow-up. In contrast, in the groups with pre-existing cervical lesions, a high incidence of VS progression was observed (63% in the AAS only group, 58% in the AAS + VS group, and 71% in the VS only group). Multivariate regression analysis demonstrated that the DAS-CRP value at baseline (odds ratio [OR] = 9.23) and matrix metaloprotease-3 level at baseline (OR = 1.01) were significant predictors for the progression of AAS, and pre-existing AAS (OR = 18.38) was a sole significant predictor for the progression of VS. CONCLUSIONS: Cervical lesions progressed irrespective of disease activity after AAS development. Strict disease control before the development of AAS is crucial for preventing further progression and development of cervical lesions.
30071898 ADAM-17 is expressed on rheumatoid arthritis fibroblast-like synoviocytes and regulates pr 2018 Aug 2 BACKGROUND: To examine the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs). METHODS: ADAM-17 expression was measured by enzyme-linked immunosorbent assays (ELISAs) in serum from normal (NL) subjects, osteoarthritis (OA) patients, and RA patients. We also analyzed the correlation between ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 in RA synovial tissues (STs) and RA FLS, we performed immunofluorescence analyses. To determine the role of ADAM-17 in RA, we transfected RA FLSs with small interfering RNA (siRNA) against ADAM-17. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was measured. Finally, adhesion molecules on ADAM-17 siRNA-transfected RA FLSs were measured using cell surface ELISAs. RESULTS: ADAM-17 in RA serum was significantly higher than that in NL and OA serum and correlated with DAS28. ADAM-17 in RA synovial fluids was higher than that in OA synovial fluids. ADAM-17 was expressed on RA cells lining STs and RA FLSs. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was decreased compared with that to control siRNA-transfected RA FLSs. ICAM-1 on TNF-α-stimulated ADAM-17 siRNA-transfected RA FLSs was significantly decreased compared with that on control siRNA-transfected RA FLSs. CONCLUSIONS: These data indicate that ADAM-17 is expressed on RA STs and plays a role in RA inflammation by regulating monocyte adhesion to RA FLSs. ADAM-17 might be an important inflammatory mediator in inflammatory diseases such as RA.
29318928 Cone-beam computed tomography, a new low-dose three-dimensional imaging technique for asse 2018 May OBJECTIVES: To determine the intra- and inter-observer agreement of erosions detected and scored with cone-beam computed tomography (CBCT) of bones in the hands and feet, and to compare CBCT with conventional radiography (CR) for assessment of bone erosions in patients with long-standing rheumatoid arthritis (RA). METHOD: Thirty patients with long-standing RA from the Better Anti-Rheumatic PharmacOTherapy (BARFOT) cohort were examined with CBCT and CR of hands and feet at their 15 year follow-up. Intra- and inter-class correlation coefficients (ICCs) were calculated. Erosions were analysed with the total rheumatoid arthritis magnetic resonance imaging erosion score (RAMRIS erosion score) for ICCs with CBCT, and with the modified RAMRIS erosion score (RAMRIS-mod.) for the same locations as used in the Sharp van der Heijde score and Sharp van der Heijde erosion score for CR. RESULTS: All 30 patients showed erosions on CBCT and 26 on CR. The ICCs for both intra- and inter-observer reliability were 0.92-0.99. CBCT showed numerically more erosions than CR for all regions compared, although a statistically significant difference was found only for the metacarpophalangeal joints [median number of eroded joints 1.0 (range 0-14) with CBCT and 0.5 (0-13) with CR, p = 0.044]. CONCLUSION: CBCT has high reproducibility and is more sensitive than CR in detecting erosions in this cohort of patients with long-standing RA. CBCT has the potential to become an important tool in the detection and follow-up of erosions in patients with RA.
29149289 Rheumatoid arthritis patients treated in trial and real world settings: comparison of rand 2018 Feb 1 OBJECTIVE: To investigate whether patients with RA enrolled in randomized controlled trials (RCTs) and observational studies may differ in terms of characteristics that could modify treatment effects, leading to an efficacy-effectiveness gap. METHODS: We conducted systematic literature reviews to identify RCTs and observational studies with RA, treated with rituximab, tocilizumab or etanercept. We extracted baseline characteristics and compared the data of RCTs and observational studies using fixed-effects meta-analyses for the RCTs and random-effects meta-analyses for the observational studies. We also assessed whether the baseline characteristics changed over time. RESULTS: Compared with patients enrolled in RCTs, those from observational studies were on average 3.0 years older (P < 0.001), suffered from RA for 3.1 years longer (P < 0.001), had 1.6 more prior disease modifying drugs (P = 0.001), and had a lower DAS-28 (difference -0.6, P < 0.001). CRP and ESR levels were slightly higher in RCTs. The HAQ-Disability Index (HAQ-DI) score was slightly lower in the RCT group. No differences were found in the percentages of included females or RF positivity. Over time, we found a significant decrease of - 0.08 in DAS-28 and a decrease of - 0.04 in HAQ-DI both in patients in RCTs and in patients from registries. Furthermore, ESR and CRP declined over time in RCT patients, but not in patients participating in observational studies. CONCLUSION: There are substantial systematic differences in patient characteristics between RCTs and registries in RA. The efficacy seen in RCTs may not reflect real-world effectiveness.