Browse

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

ID PMID Title PublicationDate abstract
28630785 Assessment of Corneal Densitometry in Rheumatoid Arthritis Patients. 2017 Jun OBJECTIVES: To evaluate corneal densitometry and anterior segment parameters of rheumatoid arthritis (RA) patients and compare these results with those of age-matched healthy control subjects. MATERIALS AND METHODS: Anterior segment parameters and corneal densitometry of patients with RA and healthy control subjects were assessed by Scheimpflug corneal topography. For densitometry analysis, the 12-mm diameter area of the cornea was subdivided into four concentric radial zones and anterior, central, and posterior layers based on corneal depth. Right eyes of subjects were used for statistical analysis. RESULTS: Twenty-three consecutive patients with RA and 22 healthy control subjects were included in the study. There was no significant difference with regard to age (p=0.487) or gender (p=0.514). When anterior segment parameters of both groups were compared, no significant difference was found (p>0.05). Total corneal densitometry values were statistically higher in the RA group (p=0.030). In addition, when subdivisions of the cornea were evaluated, higher densitometry values were found in the RA group in 0-2 and 2-6 mm radial zones both in the anterior and total depth (p=0.001, p=0.003 for the 0-2 mm zone and p=0.002, p=0.009 for the 2-6 mm zone). Corneal densitometry measurement was not correlated with central corneal thickness or simulated keratometry value in RA patients or healthy control subjects. CONCLUSION: The corneal densitometry values were higher in RA patients when compared to healthy control subjects, even if they had clinically clear corneas. Corneal densitometry as an objective measure of corneal clarity warrants further studies in order to ascertain its clinical relevance in RA patients.
28405469 What causes a small increase in radiographic progression in rheumatoid arthritis patients 2017 OBJECTIVE: In a randomised controlled trial investigating tapering of TNF inhibitors (TNFi) compared with usual care (UC) in rheumatoid arthritis patients, minimal radiographic progression was more frequent in patients who attempted tapering. Possible explanations include higher incidence of flaring, higher mean disease activity or lower TNFi use. METHODS: 18 months data from the DRESS study were used. Change in Sharp-van der Heijde (ΔSvdH) score (linear regression) and proportion of patients with >0.5 ΔSvdH (logistic regression) were used as outcomes. The cumulative incidence and number of short-lived and major flares per patient, mean time-weighted disease activity (MTW-DAS28-CRP) and TNFi use were used as independent variables. Regression models were performed stratified per study group and corrected for possible confounders. RESULTS: 175 of 180 patients had 18-month data available. The mean ΔSvdH were 0.75 and 0.15 units with 37 of 116 (32%) and 9 of 59 (15%) patients exceeding 0.5 points in the tapering and UC group, respectively (both p<0.05). MTW-DAS28-CRP, but not incidence or number of short-lived or major flares, or TNFi use, was independently associated with the mean progression score, but only in the tapering group. Additional analyses on DAS28-CRP subcomponents showed that this was mainly caused by MTW swollen joint count. No confounders were identified. CONCLUSIONS: Radiographic progression was associated with higher MTW-DAS28-CRP (and especially swollen joint count), but only in patients who tapered TNFi. This finding stresses the importance of maintaining disease activity as low as possible in patients in whom TNFi is tapered and to check for radiographic progression regularly. TRIAL REGISTRATION NUMBER: NTR 3216; Post-results.
29900992 The Relationship Between Serum Pentraxine 3 Levels and Hematological Markers in Patients W 2018 Mar OBJECTIVES: This study aims to investigate the association of pentraxin 3 (PTX3) with neutrophil/lymphocyte ratio (NLR) rather than the disease activity score 28 using C-reactive protein in rheumatoid arthritis (RA). PATIENTS AND METHODS: The study included 59 RA patients (11 males, 48 females; mean age 53.79±13.55 years; range 40 to 66 years) and 20 healthy controls (5 males, 15 females; mean age 50.41±6.11 years; range 43 to 56 years). Complete blood count tests were recorded and NLR and platelet/ lymphocyte ratio were calculated. PTX3 and interleukin-6 levels were examined in serum samples. Disease activity of RA patients was assessed by disease activity score 28. RESULTS: Demographic characteristics were similar between the two groups, with no statistically significant difference in terms of sex, age, and body mass index (p>0.05). NLR, PTX3 and interleukin-6 levels were higher in patients with RA than the control group (p<0.05). While erythrocyte sedimentation rate had a positive correlation with mean platelet volume, we found no correlation between NLR and other parameters of disease activity, PTX3, and interleukin-6. CONCLUSION: We found no correlation between PTX3 and disease activity score 28 or NLR, although PTX3 levels were higher in RA patients than the controls. As a result, we were unable to establish a relationship between PTX3 and disease activity, directly or indirectly. To our knowledge, our study was the first to investigate the relationship between PTX3 and NLR.
29326847 Corneal, Scleral, Choroidal, and Foveal Thickness in Patients with Rheumatoid Arthritis. 2017 Dec OBJECTIVES: To investigate corneal, scleral, choroidal, and foveal thicknesses in female patients with rheumatoid arthritis (RA) and compare them with healthy subjects. MATERIALS AND METHODS: This prospective study included consecutive female patients diagnosed with RA and healthy subjects. Corneal, scleral, choroidal, and retinal (foveal) thicknesses were obtained by using optical coherence tomography and a comparison was performed between groups for all outcome measures. RESULTS: Thirty-six eyes of 36 female patients diagnosed with RA (group 1) and 36 eyes of 36 healthy female volunteers (group 2) were included. Mean corneal, scleral, choroidal thicknesses and retinal thickness at the fovea of group 1 were 543.3±33.7 µm, 343.7±42.2 µm, 214.6±50, and 213.5±18.9 µm, respectively; in group 2, these values were 549.9±29.6 μm, 420.9±42.4 μm, 206.4±41.9 μm, and 222±15.5 μm, respectively. The comparison between group 1 and 2 with respect to corneal, choroidal, and foveal thicknesses did not reveal statistical significant differences (p>0.05). On the contrary, there was a statistically significant difference with respect to scleral thickness between the groups, with the RA patients demonstrating a thinner scleral layer (p<0.001). CONCLUSION: Female patients with RA seem to demonstrate statistically significant scleral thinning when compared with healthy subjects, while there was no difference concerning corneal, choroidal, and foveal thickness.
29289647 Resilience in women with autoimmune rheumatic diseases. 2018 Dec OBJECTIVE: To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. METHODS: Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. RESULTS: Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (<48years) with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis who had low socioeconomic status, whereas older patients (>50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. CONCLUSION: Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation.
28462482 What do people search online concerning the "elusive" fibromyalgia? Insights from a qualit 2017 Aug Fibromyalgia is a chronic disease, characterized by pain, fatigue, and poor sleep quality. Patients and mainly those with chronic diseases tend to search for health-related material online. Google Trends (GT), an online tracking system of Internet hit-search volumes that recently merged with its sister project Google Insights for Search (Google Inc.), was used to explore Internet activity related to fibromyalgia. Digital interest in fibromyalgia and related topics searched worldwide has been reported in the last 13 years. A slight decline in this interest has been observed through the years, remaining stable in the last 5 years. Fibromyalgia web behavior exhibited a regular, cyclic pattern, even though no seasonality could be detected. Similar findings have been reported among rheumatoid arthritis and depression. However, differently from rheumatoid arthritis and depression, the focus of the fibromyalgia-related queries was more concentrated on drug side effects and the "elusive" nature of fibromyalgia: is it a real or imaginary condition? Does it really exist or is it all in your head? A tremendous amount of information on fibromyalgia and related topics exist online. Still many queries have been raised and repeated constantly by fibromyalgia patients in the last 13 years. Therefore, physicians should be aware of the common concerns of people or patients regarding fibromyalgia in order to give a proper answers and education.
28353191 Long-Term Maintenance of Certolizumab Pegol Safety and Efficacy, in Combination with Metho 2017 Jun INTRODUCTION: The safety and efficacy of certolizumab pegol (CZP) 400 mg every 4 weeks (Q4W) monotherapy (FAST4WARD/NCT00548834) and in combination with methotrexate (MTX) (014/NCT00544154) in active rheumatoid arthritis (RA) has been published previously. This report outlines final long-term outcomes from the open-label extension (OLE) study (015/NCT00160693), which enrolled patients from these randomized controlled trials (RCTs). METHODS: Patients who withdrew from or completed the 24-week 014/FAST4WARD RCTs were enrolled and received CZP 400 mg Q4W with/without MTX. Exposure-adjusted event rates (ER) per 100 patient-years (PYs) of adverse events (AEs) and serious AEs (SAEs) were reported for all patients receiving ≥1 dose of CZP in RCTs or OLE (N = 427) between first CZP dose and up to 24 weeks after last CZP dose or study withdrawal. Efficacy assessments included clinical (ACR20/50/70 response rates, TJC, SJC) and patient-reported outcomes (HAQ-DI, PtGADA, pain, fatigue) to week 304 (5.8 years) in the CZP intent-to-treat population. SDAI and CDAI outcomes were analyzed post hoc. Outcomes for CZP monotherapy and CZP+MTX combination-therapy were compared. RESULTS: Globally, ERs of AEs and SAEs were 408.1 and 25.2 per 100 PY, respectively. Eleven patients had AEs leading to death (ER 0.6). Improvements in clinical and patient-reported outcomes during the 24-week RCTs were maintained to week 304, and were similar between all subpopulations. CONCLUSIONS: The longest exposure duration to date with CZP 400 mg Q4W treatment confirmed the safety profile observed in previous studies. Initial improvements in signs and symptoms of RA, including PROs, were maintained in both CZP monotherapy and CZP + MTX combination-therapy patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT00160693. FUNDING: UCB Pharma.
28819701 Suppressive Effects of TSAHC in an Experimental Mouse Model and Fibroblast-Like Synoviocyt 2017 Dec The purpose of this study is to investigate the effect of TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] in K/BxN serum transfer arthritis model and fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS). In in vivo experiments, TSAHC attenuated the incidence and severity of arthritis in comparison with the vehicle group. Histological findings showed that TSAHC decreased the inflammation, bone erosion, cartilage damage, and osteoclasts activity in the ankle. Furthermore, we confirmed by biochemical analysis that the observations were associated with the decreased expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and RANKL in serum and ankle. In in vitro experiments, TSAHC induced apoptosis, while it significantly suppressed tumor necrosis factor-α (TNF-α)-induced cell proliferation in RA-FLS. Moreover, TSAHC inhibited mRNA expression of TNF-α-induced interleukin (IL)-6, MMP-1, MMP-3, and MMP-13. Evaluation of signaling events showed that TSAHC inhibited the translocation and transcriptional activity of nuclear factor-kappa B (NF-κB) by regulating phosphorylated-IκB-α (p-IκB-α) and IκB-α in TNF-α-induced RA-FLS. Our results suggest that TSAHC inhibits experimental arthritis in mice and suppresses TNF-α-induced RA-FLS activities via NF-κB pathway. Therefore, TSAHC may have therapeutic potential for the treatment of RA.
28469936 Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULA 2017 OBJECTIVE: To determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients. METHODS: A prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome. RESULTS: Of 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion. CONCLUSIONS: This is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression.
28524764 Lack of Association between STAT4 Single Nucleotide Polymorphisms and Iranian Juvenile Rhe 2017 Jun Juvenile rheumatoid arthritis (JRA) is a common chronic systemic autoimmune disease in children. Single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT4) gene are suspected to have association with the risk of autoimmune diseases. Previous investigations have indicated that the STAT4 rs7574865 T allele was significantly associated with rheumatoid arthritis. In this study, we aimed to evaluate the association of STAT4 SNPs with JRA in Iranian population. T allele of STAT4 rs7574865 SNP was less frequent in patients than in controls, and the difference was not significant (p = 0.19, OR = 0.72, 95% CI: 0.44 -1.17). In addition, G allele of this SNP was frequent but not significant in JRA patients (p = 0.19, OR = 1.38, 95% CI: 0.85-2.25). Neither alleles nor genotypes of rs7601754 SNP of STAT4 gene demonstrated associations with JRA. We recognize that gene variants of STAT4 did not affect JRA susceptibility in Iranian population.
29177081 Impact of gender on the response and tolerance to abatacept in patients with rheumatoid ar 2017 OBJECTIVE: The impact of gender on the response and tolerance to abatacept was assessed in a large prospective cohort during 2 years of follow-up. METHODS: From the 1017 patients included in the Orencia and Rheumatoid Arthritis registry, disease activity was assessed at baseline, 6, 12 and 24 months. The relationship between the European League Against Rheumatism (EULAR) response, Disease Activity Score 28 (DAS28) remission, rate of adverse events and gender was explored in multivariate analysis. RESULTS: 990 patients, 79.3%female, with at least one follow-up visit were analysed. At baseline, women had longer disease duration, higher disease activity and more often received antitumour necrosis factor (TNF) drugs. The remission was not different between men and women during the follow-up after adjustment on age, disease duration and activity, rheumatoid factor and anti-cyclic citrullinated pyeptide (CCP) positivity, and current disease-modifying antirheumatic drugs (DMARDs), previous TNF blockers and corticosteroids use. The proportion of men and women achieving EULAR good-or-moderate response at any endpoints was similar (52.4% vs 55.5%), as well as time to achieving EULAR response (5.4±4.9 vs 5.6±5.2 months). Moderate EULAR response was more frequent in women at 6 months (OR=1.80, p=0.02) but was no longer significant at 12 or 24 months. During the follow-up, the DAS28, the tender joint count score and the patient global assessment remained higher in women (p=0.001, 0.04 and 0.06, respectively). Drug retention and safety were comparable. CONCLUSION: In this large daily practice cohort of established rheumatoid arthritis treated with abatacept, women achieved similar remission and EULAR response than men despite higher disease activity and tender joint count during the treatment course.
29299338 Synovial tissue macrophages: friend or foe? 2017 Healthy synovial tissue includes a lining layer of synovial fibroblasts and macrophages. The influx of leucocytes during active rheumatoid arthritis (RA) includes monocytes that differentiate locally into proinflammatory macrophages, and these produce pathogenic tumour necrosis factor. During sustained remission, the synovial tissue macrophage numbers recede to normal. The constitutive presence of tissue macrophages in the lining layer of the synovial membrane in healthy donors and in patients with RA during remission suggests that this macrophage population may have a role in maintaining and reinstating synovial tissue homeostasis respectively. Recent appreciation of the different origins and functions of tissue-resident compared with monocyte-derived macrophages has improved the understanding of their relative involvement in organ homeostasis in mouse models of disease. In this review, informed by mouse models and human data, we describe the presence of different functional subpopulations of human synovial tissue macrophages and discuss their distinct contribution to joint homeostasis and chronic inflammation in RA.
29037901 HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta- 2017 Dec Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis.
28732491 Job retention vocational rehabilitation for employed people with inflammatory arthritis (W 2017 Jul 21 BACKGROUND: Inflammatory arthritis leads to work disability, absenteeism and presenteeism (i.e. at-work productivity loss) at high cost to individuals, employers and society. A trial of job retention vocational rehabilitation (VR) in the United States identified this helped people keep working. The effectiveness of this VR in countries with different socioeconomic policies and conditions, and its impact on absenteeism, presenteeism and health, are unknown. This feasibility study tested the acceptability of this VR, modified for the United Kingdom, compared to written advice about managing work problems. To help plan a randomized controlled trial, we tested screening, recruitment, intervention delivery, response rates, applicability of the control intervention and identified the relevant primary outcome. METHODS: A feasibility randomized controlled trial with rheumatoid, psoriatic or inflammatory arthritis patients randomized to receive either job retention VR or written information only (the WORK-IA trial). Following three days VR training, rheumatology occupational therapists provided individualised VR on a one to one basis. VR included work assessment, activity diaries and action planning, and (as applicable) arthritis self-management in the workplace, ergonomics, fatigue and stress management, orthoses, employment rights and support services, assistive technology, work modifications, psychological and disclosure support, workplace visits and employer liaison. RESULTS: Fifty five (10%) people were recruited from 539 screened. Follow-up response rates were acceptable at 80%. VR was delivered with fidelity. VR was more acceptable than written advice only (7.8 versus 6.7). VR took on average 4 h at a cost of £135 per person. Outcome assessment indicated VR was better than written advice in reducing presenteeism (Work Limitations Questionnaire (WLQ) change score mean: VR = -12.4 (SD 13.2); control = -2.5 (SD 15.9), absenteeism, perceived risk of job loss and improving pain and health status, indicating proof of concept. The preferred primary outcome measure was the WLQ, a presenteeism measure. CONCLUSIONS: This brief job retention VR is a credible and acceptable intervention for people with inflammatory arthritis with concerns about continuing to work due to arthritis. TRIAL REGISTRATION: ISRCTN 76777720 . Registered 21.9.12.
28496328 Association between use of disease-modifying antirheumatic drugs and diabetes in patients 2017 PURPOSE: The aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PSA). PATIENTS AND METHODS: This retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM. RESULTS: The incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36-0.66) and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63-0.78), but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94-1.60) or CSA (aHR: 1.14, 95% CI: 0.77-1.70). CONCLUSION: The aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk of DM.
29081988 Infection rates in patients from five rheumatoid arthritis (RA) registries: contextualisin 2017 OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of serious infections. Comparing infection rates across RA populations is complicated by differences in background infection risk, population composition and study methodology. We measured infection rates from five RA registries globally, with the aim to contextualise infection rates from an RA clinical trials population. METHODS: We used data from Consortium of Rheumatology Research of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (Sweden), Norfolk Arthritis Register (UK), CORRONA International (multiple countries) and Institute of Rheumatology Rheumatoid Arthritis (Japan) and an RA clinical trial programme (fostamatinib). Within each registry, we analysed a main cohort of all patients with RA from January 2000 to last available data. Infection definitions were harmonised across registries. Sensitivity analyses to address potential confounding explored subcohorts defined by disease activity, treatment change and/or prior comorbidities and restriction by calendar time or follow-up. Rates of infections were estimated and standardised to the trial population for age/sex and, in one sensitivity analysis also, for Health Assessment Questionnaire (HAQ) score. RESULTS: Overall, age/sex-standardised rates of hospitalised infection were quite consistent across registries (range 1.14-1.62 per 100 patient-years). Higher and more consistent rates across registries and with the trial programme overall were seen when adding standardisation for HAQ score (registry range 1.86-2.18, trials rate 2.92) or restricting to a treatment initiation subcohort followed for 18 months (registry range 0.99-2.84, trials rate 2.74). CONCLUSION: This prospective, coordinated analysis of RA registries provided incidence rate estimates for infection events to contextualise infection rates from an RA clinical trial programme and demonstrated relative comparability of hospitalised infection rates across registries.
30645882 [ω-3 polyunsaturated fatty acids use for optimization of children inflammatory joints dis 2017 The use of additional treatment methods in inflammatory joints disease therapy is very important. But the main principles of diet therapy for patients with rheumatoid joint inflammation and reactive arthritis and possibility of focused impact on disease activity by means of alimentary factors have not still been formed out. The aim of the investigation was to study the effect of diet therapy including ω-3 polyunsaturated fatty acids (PUFAs) on joint syndrome evidence and on bone turnover markers of children with inflammatory joint diseases. With parents' agreement children aged 5-16 hospitalized with inflammatory joint diseases (53 with juvenile rheumatoid arthritis and 35 with reactive arthritis) were enrolled in this research. According to the treatment mode 2 subgroups were separated in each group: the first subgroup underwent backbone therapy, the second - backbone therapy along with ω-3 PUFAs (cod liver oil 1000 mg containing 115 mg of docosahexaenoic and 23 mg of eicosapentaenoic acids). Children aged 3-5 years received 1 capsule 2 times a day, over 6 years old - 1 capsule 3 times per day with meals for 3 months. Disease activity, joint syndrome evidence (counting of joint pain, Ritchie index, number of inflammatory joints, morning stiffness duration) and biochemical values of connective tissue metabolism were estimated while being introduced into research and at the end of treatment. More apparent improvement of joint syndrome indexes at the end of supervision was diagnosed in the groups undergoing backbone therapy along with ω-3 PUFAs. Statistically significant (p<0.05) reduce of morning stiffness time by 3 fold vs 2 fold in children treated with basic therapy, reduce of joint index by 2.9-5.7 fold vs 2.0-3.8 fold, the number of inflammatory joints by 4.5-5.8 fold vs 2.0-2.3 fold, blood serum level of hydroxyl proline and antibodies to rumalon were observed in main groups of patients. Disease activity index DAS 4 decreased in the group undergoing backbone therapy by 0.44 (p<0.05) and in the group undergoing modified therapy - by 1.20 (p<0.05). No adverse effects of PUFAs have been observed. It was concluded that ω-3 PUFAs increased the action of basic therapy favoring advances in inflammatory process activity control, provided decrease of non-steroidal antiinflammatory drugs (NSAID) intake and proved to be an important supplement in diet therapy of children inflammatory joints diseases.
28056924 Anti-arthritic activity of ethanol extract of Claoxylon indicum on Freund's complete adjuv 2017 Jan 5 BACKGROUND: Claoxylon indicum Hassk. (Euphorbiaceae), named Diu Le Bang, have functions of dehumidification and relieving swelling pain, and is used as a folk medicine to treat Rheumatoid arthritis (RA), lumbocrural pain and foot edema in the south of China. The aim of the present study was to investigate the anti-arthritic activity of the ethanol extract of Claoxylon indicum (CIE) on mice with adjuvant induced joint arthritis. METHODS: Adjuvant arthritis was induced in mice by subcutaneous injection of complete Freund's adjuvant into the plantar surface of right hind paw. Arthritis severity was evaluated by arthritic score, hind paws oedema and spleen index, and histological examinations. Serum samples were collected for determination of malondialdehyde (MDA) and alkaline phosphatase (ALP) levels. The expression of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in the specimens of knee joints was determined by standard immunohistochemical techniques. RESULTS: CIE administration (0.4 and 0.8 g/kg) suppressed the inflammatory responses in the joints of adjuvant-induced arthritis (AIA) mice, suggested by the modulatory effects on paw swelling, hyperplasia of lymphatic tissues and synovial membrane. It also decreased the levels of MDA and ALP in serum and downregulated the expression of IL-1β and TNF-α in the arthritic joints of AIA mice. CONCLUSION: These results suggested that CIE possessed substantial anti-arthritic activity due to immumodepression and regulation of cytokines. CIE may be a potential candidate for the treatment of RA.
28993780 Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 2017 Autoantibodies directed against citrullinated epitopes of proteins are highly diagnostic of rheumatoid arthritis (RA), and elevated levels of protein citrullination can be found in the joints of patients with RA. Calcium-dependent peptidyl-arginine deiminases (PAD) are the enzymes responsible for citrullination. PAD2 and PAD4 are enriched in neutrophils and likely drive citrullination under inflammatory conditions. PADs may be released during NETosis or cell death, but the mechanisms responsible for PAD activity under physiological conditions have not been fully elucidated. To understand how PADs citrullinate extracellular proteins, we investigated the cellular localization and activity of PAD2 and PAD4, and we report that viable neutrophils from healthy donors have active PAD4 exposed on their surface and spontaneously secrete PAD2. Neutrophil activation by some stimulatory agents increased the levels of immunoreactive PAD4 on the cell surface, and some stimuli reduced PAD2 secretion. Our data indicate that live neutrophils have the inherent capacity to express active extracellular PADs. These novel pathways are distinguished from intracellular PAD activation during NETosis and calcium influx-mediated hypercitrullination. Our study implies that extracellular PADs may have a physiological role under non-pathogenic conditions as well as a pathological role in RA.
29077164 Macrophage activation syndrome as a complication of juvenile rheumatoid arthritis. 2017 Oct OBJECTIVE: Juvenile rheumatoid arthritis (JRA), also known as juvenile idiopathic arthritis (JIA), is a rare autoimmune joint disorder of children. The concrete causes for the prevalence of the above pathological state are still unknown. In other words, it is an arthritis affecting mainly children and adolescents. Clinically, it has 3 different clinical subtypes. JRA patients are often noticed with some confirmed symptoms including coagulopathy, disseminated intravascular coagulation (DIC) with hepatosplenomegaly, fall in erythrocyte sedimentation rate and higher levels of liver enzymes leading to a life-threatening outcome. The above complications of JRA are recognized as a macrophage activation syndrome (MAS), which is similar to hemophagocytic lymphohistiocytosis (HLH). Pathogenesis of JRA manly involves deregulation of immunological processes with excessive and persistent activation of antigen presenting cells and T-lymphocytes. Further, abnormalities in the functioning of NK cells are often observed in JIA cases. Also, 40% of patients with these abnormalities are habitually associated with perforin gene mutations. Today, MAS remains a clinical and diagnostic challenge. RESULTS: The diagnosis of MAS is mainly based on clinical grounds. However, laboratory evidence of macrophages in the bone marrow performing phagocytosis of variable hematopoietic cells also help in diagnosis. For confirmation of MAS, there must be present either of two clinical or laboratory criteria. Further, laboratory criteria often appear late and are unable to diagnose the complication right at the beginning stage. Important laboratory findings in macrophage activation syndrome associated with JIA include hypertriglyceridemia, anemia, low erythrocyte sedimentation rate, elevated alanine aminotransferase level, higher than normal bilirubin levels, presence of fibrin degradation products, high lactate dehydrogenase level, low sodium, low albumin, and hyperferritinemia. CONCLUSIONS: MAS is a confirmed life threatening complication of patients with JIA. Further, an early diagnosis and treatment of MAS could be a life-saving mode for this syndrome.