Open Rheumatology Journal最新文献

Background: Primary Osteoarthritis (OA) is a multifactorial disease in which genetic factors are strongly associated with its development; however, recently it has been observed that epigenetic modifications are also involved in the pathogenesis of OA. DNA methylation is related to gene silencing, and several studies have investigated its role in the loci of different pathways or molecules associated to OA.

Objective: This review is focused on the current status of DNA methylation studies related to OA pathogenesis.

Method: A review of the literature was conducted on searching in PUBMED for original papers on DNA methylation in OA.

Conclusion: The DNA methylation research of loci related to OA pathogenesis has shown a correlation between methylation and gene repression; however, there are some exceptions to this rule. Recently, the development of genome-wide methylation and genome-wide hydroxymethylation profiles has demonstrated that several genes previously associated with OA can have changes in their methylation status, favoring the development of the disease, and these have even shown the role of other epigenetic markers.

Introduction: Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls.

Materials and methods: Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited. PBMCs were cultured with 5µg/ml, 50µg/ml or without any TDB for 48 hours in RPMI medium inside a 5% Co2 incubator. IL-6, TNF-α and IL-17 were measured in cell culture supernatant, which was separated from the cells at the end of the incubation period. Gene expressions of IL-6, IL-8, TNFα, IFN-γ, MINCLE and BCL-10 were quantified in real time PCR using specific primers and SYBR green chemistry.

Results: Twenty two TA patients and 21 healthy controls were recruited. Both patients and controls showed response by secreting IL-6 and TNF-α upon stimulation by TDB. Relative induction (TDB stimulated TA sample / unstimulated control) of IL-6 was significantly higher in TA [31.88(0.74-168)] patients as compared to healthy controls [1.931(0.644-8.21); p<0.002], when co-cultured with 50µg/ml TDB. The expression of MINCLE, the TDB receptor was higher in TA samples than healthy controls upon TDB stimulation.

Conclusion: Stimulation with mycobacterial synthetic analogue led to higher secretion of IL-6 and higher expression of MINCLE in PBMCs of patients with TA as compared to healthy controls.

Objectives: The study aimed to demonstrate the interethnic differences and clinical features of Spondyloarthropathy(SpA) patients in a diverse Middle Eastern Country.

Methods: A retrospective review of medical records to collect the required data was conducted for SpA patients at two study institutions in the United Arab Emirates.

Results: Of 141 SpA patients found, 88 AS(Ankylosing Spondylitis) patients and 53 'other SpA' patients were identified. Males constituted 81% of AS and 55% of 'other SpA' patients. Patients with AS and 'other SpA' had a mean age of symptom onset of 28 and 34 years, respectively.49% and 40% of AS and 'other SpA' patients had a history of Anti-TNF therapy usage. Enthesitis and Uveitis were noted in 16% and 18% of AS patients whilst 53% and 11% in 'other SpA' patients, respectively.Caucasian, Indian Subcontinent and Arabs constituted 93% of our cohort. Mean age of onset of symptoms in the Indian Subcontinent 'other SpA' group was much greater than the other two ethnicities. Duration of symptoms to diagnosis was 3.5 and 4 years in AS and other SpA patients' respectively. HLA-B27 positivity was found in 53%, 80% and 93% of Arab, Indian Subcontinent and Caucasian AS patients, respectively, whilst seen in 50%, 25% and 33% of the same respective ethnicties in 'other SpA' patients.

Conclusion: This study on 141 patients is the largest to analyse inter-ethnic variations in SpA patients in the region. Our cohort shows a short delay in diagnosis with a relatively higher Anti-TNF usage.

Background: In the past two decades, Vitamin K has been receiving more attention due to its role in bone health and metabolism. The bone mineral density does not remain steady with age, particularly declining after menopause.

Objective: This study is aimed to investigate the relationship between bone mineral density and serum vitamin K1 levels in post-menopausal women, and to evaluate serum vitamin K1 levels as a potential biomarker for postmenopausal osteoporosis.

Methods: Serum levels of vitamin k1 were measured in 23 postmenopausal osteoporotic women, and in 15 postmenopausal healthy control women using a standardized Enzyme-Linked Immune Sorbent Assay (ELISA) kit. Bone mineral density BMD was assessed at the lumbar spine.

Results: The mean serum vitamin k1 level was significantly lower in the postmenopausal osteoporotic women group than in the normal control group (mean=0.794 vs3.61ng/ml, P< 0.0001), and serum vitamin k1 concentration was positively correlated with lumbar spine BMD among postmenopausal osteoporotic women (R=0.533, p = 0.009), and in postmenopausal healthy control (R=0.563, p = 0.02).Diagnostic sensitivity and specificity of vitamin k1 for osteoporosis were 90% and 98%, respectively (cut-off value: 0.853 ng/ml). The area under the ROC curve (AUC) value for vitamin k1 was 0.984 the odd ratio result was 18.66.

Conclusion: Our results suggest that vitamin K1 may contribute to maintain bone mineral density. Vitamin K1 may have a role in diagnosing post-menopausal osteoporosis. Vitamin K1 may be a valuable diagnostic as well as therapeutic marker in post-menopausal osteoporosis.

Background: Early treatment of rheumatoid arthritis (RA) results in better long-term outcomes. However, the optimal therapeutic window has not been clearly established.

Objective: To determine the clinical outcome of Puerto Ricans with RA receiving early treatment with conventional and/or biologic disease-modifying anti-rheumatic drugs (DMARDs) based on the American College of Rheumatology (ACR) definition of early RA.

Methods: A cross-sectional study was performed in a cohort of Puerto Ricans with RA. Demographic features, clinical manifestations, disease activity, functional status, and pharmacotherapy were determined. Early treatment was defined as the initiation of DMARDs (conventional and/or biologic) in less than 6 months from the onset of symptoms attributable to RA. Patients who received early (< 6months) and late (≥6 months) treatments were compared using bivariate and multivariate analyses.

Results: The cohort comprised 387 RA patients. The mean age at study visit was 56.0 years. The mean disease duration was 14.9 years and 337 (87.0%) patients were women. One hundred and twenty one (31.3%) patients received early treatment. In the multivariate analysis adjusted for age and sex, early treatment was associated with better functional status, lower probability of joint deformities, intra-articular injections and joint replacement surgeries, and lower scores in the physician's assessments of global health, functional impairment and physical damage of patients.

Conclusion: Using the ACR definition of early RA, this group of patients treated with DMARDs within 6 months of disease had better long-term outcomes with less physical damage and functional impairment.

Objective: To compare anti-TNF dose escalation, DMARD and/or glucocorticoid intensification, switches to another biologic, and drug and drug-related costs over 12 and 18 months for rheumatoid arthritis (RA) patients initiating etanercept (ETN), adalimumab (ADA), or infliximab (IFX) in routine clinical practice across Canada.

Methods: A retrospective chart review of biologic-naïve adult RA patients newly initiating ADA, ETN, or IFX between January 01, 2006 and December 31, 2012 from 11 practices across Canada.

Results: There were 314 patients in the 12-month analysis and 217 in the 18-month analysis. No dose escalation occurred with ETN over 12 and 18 months versus 38% and 32% for IFX (p<0.001) and 2% and 2% for ADA (p=0.199, p=0.218). Over 18 months, dose escalation and/or DMARD and/or glucocorticoid intensification was less frequent among ETN (16%) versus IFX (44%, p=0.005) and ADA (34%, p=0.004). By 18 months, 22% of patients initiating ADA had switched to another biologic compared with 6% of ETN patients (p=0.001).Patients initiating ETN had lower total (drug and drug-related) costs over 12 and 18 months compared to IFX, and no difference compared to ADA when adjusted for potential confounders. Patients with dose escalation had higher costs compared to those with no dose escalation.

Conclusion: Physicians were more likely to escalate the dose of IFX, but optimize co-therapy with ADA and ETN. ETN patients had no dose escalation and were less likely to have DMARD and/or glucocorticoid intensification than ADA patients. ETN-treated patients had lower costs compared to IFX patients.

Objectives: The Simplified Disease Activity Index (SDAI) 50 has good agreement with European League Against Rheumatism (EULAR) response measures for early Rheumatoid Arthritis (RA). There have been reports on early RA, but not on long-established RA. In this study, we analysed the relationships between various baseline factors and SDAI 50 after three months of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) to determine the prognostic factors for long-established RA.

Methods: Subjects were 260 RA patients who had been treated with bDMARDs for 3 months. The following characteristics were investigated: Patient backgrounds, the erythrocyte sedimentation rate (ESR), C-reactive protein and serum matrix metalloproteinase-3 levels, SDAI scores, and health assessment questionnaire disability index and short form-36 scores. As a primary outcome index, the SDAI response was defined as a 50% reduction in the SDAI score between baseline and 3 months (SDAI 50).

Results: Baseline values of disease duration (odds ratio: 0.942, 95% CI: 0.902-0.984), smoking history (odds ratio: 2.272, 1.064-4.850), 28-tender joint count (odds ratio: 0.899, 0.827-0.977), evaluator's global assessment (odds ratio: 1.029, 1.012-1.047) and ESR (odds ratio: 1.015, 1.001-1.030) were determined to be significant factors based on logistic regression analysis.

Conclusion: Our study demonstrated that RA patients with shorter disease duration, no smoking, and higher RA disease activity are more likely to achieve SDAI 50 through bDMARD treatment.

Background: Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3-1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development.

Objective: The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a "double-hit" phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production.

Method: A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption.

Conclusion: We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology.

Background: The Infliximab, has proven effective in treating rheumatoid arthritis (RA). A good clinical response is usually associated with high serum drug levels. Development of antibodies toward Infliximab (ATI) can increase drug clearance, leading to treatment failure.

Aims: To analyze whether serum Infliximab trough levels (ITL) at the induction phase are associated with Infliximab clearance and clinical outcomes at week(W) 54 and to investigate the association with immunogenicity development.

Methods: Observational retrospective study in which ITL from 66 RA patients were measured by capture ELISA at W0, W2, W6, W14 and 22. Patients were classified as ITLpos if Infliximab was detectable at W54 and ITLneg otherwise. ATI were assayed by bridging ELISA and by two drug-tolerant assays. ITL cut-off values were established by ROC curves. The association between ITL at early-stage and clearance of Infliximab at W54 was analyzed by univariable and multivariable logistic regression.

Results: ITLneg patients (n=25) always had significantly lower Infliximab levels than ITLpos (n=41). An ITL value of 4.4 μg/mL at W6 best predicted W54 Infliximab absence. In the multivariable analysis, only ITL below the cut-off at W6 (OR: 86.6; 95%CI: 6.58-1139.99) and non-use of methotrexate (OR: 6.9; 95%CI: 1.04-45.84) remained significantly associated with W54 Infliximab absence. ATI were more frequent in patients with ITL below the cut-off at W6.

Conclusions: In RA, ITL at induction phase are inversely associated with Infliximab clearance and clinical outcomes at W54. ATI was the main reason for low early ITL. A predictive value of ITL at W6 was found as a useful prognostic measure of treatment efficacy.

Background: Smoking is one of the main environmental risk factors involved in several rheumatic diseases according to ACR 2014, it is included among the risk factors for severe axial spondyloarthritis.

Objectives: The objective is to study the association between smoking and the activity of the disease, the functional impact and the severity of the axial spondyloarthritis.

Methods: It is a transversal study with a descriptive and analytical aim, during the period between January 2014 and December 2015 conducted in the department of rheumatology at the CHU Hassan II of Fes. The data was recorded and analyzed using SPSS v20 univariate and bivariate analysis A value of p <0.005 has been used to identify factors associated with smoking.

Results: The study included 214 patients, 130 men and 84 women. The mean age was 39.77 ± 13.06 (16-68) years with an average disease duration of 7.97 ± 6.4 (2-35) years. The prevalence of smoking in patients with spondyloarthritis was 36%. According to the univariate and bivariate analysis: Smoking was associated with the male sex (p≤0.0001), with a functional impairment BASFI (p = 0.038) and activity BASDAI (p=0.004) and ASDAS CRP, (p=0.036). Multivariate logistic regression analysis suggested that smoking was associated with male sex and the severity of the disease.

Conclusion: Our study suggests that there is a significant association between smoking and male sex and the severity of the disease.