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

ID PMID Title PublicationDate abstract
21590474 [Therapeutic strategies in rheumatoid arthritis]. 2011 Jun Rheumatoid arthritis is the most common chronic inflammatory-rheumatic joint disease. If untreated, patients develop radiologically detectable progressive joint destruction. Rheumatoid arthritis has considerable socioeconomic importance, since a majority of patients are affected at employable age and can be significantly disabled over the course of the disease. Therefore, an appropriate early intervention with disease modifying anti-rheumatic drugs as well as ergo- and physiotherapy plays an important role for the prognosis. In the past few years, the introduction of novel drugs has improved the treatment opportunities markedly. This progress was the basis for new treatment strategies of tight disease control with the goal of disease remission.
22905907 Non-Hodgkin's lymphoma of the synovium discovered in total knee arthroplasty: a case repor 2012 Aug 20 BACKGROUND: Musculoskeletal involvement occurs in 25% of patients with non-Hodgkin's lymphoma (NHL). Primary lymphoma in the joint is rare. It can present as a bone lesion or as atypical soft tissue proliferation. NHL has an increased incidence in patients with autoimmune rheumatic diseases. CASE PRESENTATION: We present a case in which non-Hodgkin's lymphoma was found coincidentally in the synovium during knee joint replacement surgery in a 69-year old woman with rheumatoid arthritis. Pigmented, vitreous tissue was resected, which turned out to be a diffuse large B-cell lymphoma after histological examination. The coincidental intraoperative finding of intra-articular non-Hodgkin's lymphoma was reported twice before, presenting as synovial proliferation in elbow and shoulder surgery. In a few other cases non-Hodgkin's lymphoma presented most often in the knee, as a bone lesion or, when soft tissue was involved, as arthritis. CONCLUSION: Non-Hodgkin's lymphoma should be considered in patients with autoimmune rheumatic diseases. In case of persistent arthritis, non-respondent to anti-inflammatory drugs, a biopsy might be warranted. Moreover, when arthroscopy or arthrotomy is planned, any atypical tissue should be sent for histological analysis. Early diagnosis of NHL can contribute to improved outcome of its rapidly developing treatment options.
22964234 Interactions of the complement system with molecules of extracellular matrix: relevance fo 2012 Nov Rheumatoid arthritis (RA) is a highly disabling disease affecting all structures of the joint. Understanding the pathology behind the development of RA is essential for developing targeted therapeutic strategies as well as for developing novel markers to predict disease onset. Several molecules normally hidden within the cartilage tissue are exposed to complement components in the synovial fluid upon cartilage breakdown. Some of these have been shown to activate complement and toll-like receptors, which may enhance an already existing inflammatory response, thereby worsening the course of disease. Other cartilage-resident molecules have in contrast shown to possess complement-inhibitory properties. Knowledge about mechanisms behind pathological complement activation in the joints will hopefully lead to methods which allow us to distinguish patients with pathological complement activation from those where other inflammatory pathways are predominant. This will help to elucidate which patients will benefit from complement inhibitory therapies, which are thought to aid a specific subset of patients or patients at a certain stage of disease. Future challenges are to target the complement inhibition specifically to the joints to minimize systemic complement blockade.
22596211 Sustained efficacy of certolizumab pegol added to methotrexate in the treatment of rheumat 2012 Sep OBJECTIVE: To evaluate the safety and efficacy of 2-year administration of certolizumab pegol (CZP) + MTX in patients with active RA. METHODS: Patients completing 52 weeks in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 1 trial (52-week completers), or withdrawing at week 16 due to lack of ACR20 response were eligible for open-label treatment (CZP 400 mg every other week + MTX). After 2 years' treatment, HAQ-Disability Index response, ACR20/50/70 responses, DAS-28 and radiographic progression were assessed in 52-week completers. ACR20/50/70 and DAS-28 were also calculated for the intent-to-treat (ITT) population. Adverse events were assessed in patients who received one or more CZP doses during the study. RESULTS: At week 100, 88.9% (n = 216) of 52-week completers who originally received CZP 200 mg + MTX and open-label treatment remained in the study. In this group, ACR20/50/70 at week 100 were 68.2, 55.2 and 35.6%, respectively. HAQ-DI and DAS-28 improvements were sustained throughout the open-label extension (mean change -0.79 and -3.5 at week 100, respectively). A total of 46.7% (n = 113) of CZP 200 mg + MTX 52-week completers achieved low disease activity by week 100. Inhibition of radiographic progression was maintained. Similar findings were observed in 52-week completers who originally received CZP 400 mg + MTX and in the ITT population. Rates of serious infection or malignancies did not increase over time and no new safety signals were observed. CONCLUSION: CZP + MTX provided sustained, 2-year inhibition of radiographic progression and sustained improvements in RA clinical signs and symptoms, with no new safety signals observed in patients who completed 2 years of treatment. TRIAL REGISTRATION: clinicaltrials.gov, http://www.clinicaltrials.gov, NCT00175877.
22238026 Prescription for antiresorptive therapy in Mexican patients with rheumatoid arthritis: is 2013 Jan Glucocorticoids are frequently used in rheumatoid arthritis (RA) in order to alleviate symptoms of joint inflammation, retard erosions and to treat extra-articular manifestations, although these drugs may increase the risk of bone mineral loss and osteoporotic fractures. To date, in Mexico there are no studies that identify the frequency of patients with RA with corticosteroids, receiving therapy for osteoporosis. Therefore, we evaluated the prevalence and factors related to the prescription of antiresorptives in 520 Mexican patients with RA. We used a multivariate model to identify variables associated with antiresorptives prescription. We identified that although 79% of patients were under treatment with glucocorticoids, only 13% received antiresorptive agents as preventive therapy for osteoporosis. The multivariate analysis identified that higher proportions of antiresorptive drugs prescriptions were associated with female patients (OR 11.40, 95% CI: 1.5-84.3, P = 0.02), an age of 40 years or more (OR 3.22, 95% CI: 1.3-8.3, P = 0.02) and to consume a lower number of cointerventions with other drugs (OR 1.09, 95% CI: 1.0-1.2, P = 0.03). Corticosteroid treatment was not associated with the prescription of antiresorptives (P = 0.31). In conclusion, a low proportion of Mexicans with RA receive antiresorptive therapy independently regardless of whether they consume or not chronically corticosteroids. Additional strategies should be evaluated to encourage the prevention and early treatment for osteoporosis in patients with RA.
22457216 Targeting TNF receptors in rheumatoid arthritis. 2012 May Tumour necrosis factor (TNF) is a pro-inflammatory cytokine that signals through two distinct receptors, TNFR1 and TNFR2. TNF is essentially involved in the pathogenesis of various inflammatory and autoimmune diseases. Blocking TNF, in turn, has been proven to be highly effective in treating a variety of diseases. However, the role of its two receptors in these conditions is not very well understood. It is established that TNFR1 is mainly responsible for the detrimental effects of TNF. However, accumulating evidence suggests differential or even opposing effects of TNFR2 in the pathogenesis of a number of inflammatory and autoimmune conditions. In this review, we summarize the available data concerning biological and functional properties of the two TNF receptors and potential therapeutic consequences of these insights.
23190565 Demographics, clinical characteristics and predictive factors for total knee or hip replac 2013 Mar OBJECTIVES: This paper aims to study the prevalence of total knee and hip replacements in Greek patients with rheumatoid arthritis (RA) and to identify possible predictive factors for future total hip or knee replacement. METHODS: A retrospective medical record review was performed in 750 RA patients who were recruited during 1994 to 2008 in a single Greek medical centre. Of the reviewed patients, 489 with a minimum follow-up duration of 1 year were enrolled in the study. The occurrence of total hip or knee replacement was used as the primary outcome variable in the predictive analysis. RESULTS: Total hip or knee replacement associated with RA was performed in 21 patients (4.3%). Total disease duration was the most significant factor associated with increased likelihood of total joint replacement. Erythrocyte sedimentation rate (ESR) at baseline examination was positively associated with subsequent knee or hip joint replacement (OR=1.023, 95%CI 1.005-1.04). Inadequate response to treatment was associated with a 3.12-times higher likelihood of joint replacement (95%CI, 1.28-7.58). The patients who underwent total hip or knee replacement had significantly higher ESRs and DAS 28 levels (p<0.046 and p<0.002, respectively) after the first year of follow-up. CONCLUSIONS: The identification of factors associated with total joint hip or knee replacement can improve pharmacological treatment to maintain function and prevent destruction of the affected joints. Longer disease duration and inadequate response to treatment after the first year of follow-up increases the likelihood ratio for total joint replacement during the course of disease in Greek RA patients.
20512337 Circadian rhythm and the influence of physical activity on circulating surfactant protein 2011 Dec Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed at assessing the diurnal rhythmicity and the influence of physical activity on circulating SP-D in patients with RA at different stages compared with healthy individuals. Patients with early RA (ERA) with disease duration <6 months and with long-standing RA (LRA) with disease duration 5-15 years were included in two sub-studies. Healthy individuals served as controls. Diurnal variation: blood samples were collected every 3 h from 7 a.m to 10 p.m and the following morning. Physical activity: blood sampling was done before and after standardized physical challenge. SP-D was measured by ELISA. SP-D exhibited diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P < 0.001, ERA: P = 0.004 and LRA: P = 0.009). Three hours after cessation of physical activity, SP-D decreased below pre-exercise levels in both ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P < 0.001, LRA: P < 0.001 and controls: P = 0.005). In patients with RA, the decline was already observed 1 h post-exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP-D in serum decreases following physical activity in health and RA disease. This study underscores the need of standardized blood sampling conditions in future studies on SP-D.
20369240 Rheumatoid arthritis masquerading as acromegaly recurrence: report of two cases. 2012 Sep Acromegaly is a chronic endocrinopathy characterized by hypersecretion of growth hormone (GH) and consequently of insulin-like growth factor-1 (IGF-1). The arthropathy in acromegaly is the most frequent and important cause of morbidity and functional disability in acromegaly. Rheumatoid arthritis (RA) is a rarely reported clinical situation in patients with acromegalic. We herein report 57- and 45-year-old two women, who complained bilateral, symmetric pain, swelling and morning stiffness in the joints of hands after optimal acromegaly treatment resembling acromegaly arthropathy. There was not arthralgia in other joints of the patients. Laboratory and radiological evaluations were carried out. After excluding the acromegaly activation and arthropathy by GH and IGF-1 measurement, according to clinical presentation, laboratory and radiological assessments, patients were diagnosed as RA.
22494450 What is the future of CCR5 antagonists in rheumatoid arthritis? 2012 Mar 30 Fleishaker and colleagues reported on a double-blind placebo controlled clinical trial of a C-C chemokine-receptor type 5 (CCR5) antagonist, maraviroc, in rheumatoid arthritis (RA) patients with inadequate response to methotrexate, showing that it was ineffective. Two additional CCR5 antagonists, SCH351125 and AZD5672, also failed to demonstrate clinical efficacy. In addition, CCR5-blocking antibodies could not inhibit synovial fluid-induced monocyte chemotaxis. Thus, CCR5 appears not to be a desirable target in RA treatment. Given the multiple functions of CCR5, redundancies in the chemokine system, and patient selection in the trial, we overview the recent understanding for chemokine receptor blockade in the treatment of RA
22037117 To switch or not to switch after a poor response to a TNFα blocker? It is not only a matt 2012 Jun The introduction in the therapeutic armamentarium of TNF inhibitors (TNFi) has greatly advanced the chance of obtaining a control of clinical manifestations and of structural damage progression in an important proportion of patients with rheumatoid arthritis (RA) Methotrexate (MTX)-poor responders. However not more than 50% of TNFi treated patients can reach relevant clinical benefits. Therefore the unmet medical question is: should we continue the therapeutic approach with a second or a third TNFi, or should we use other drugs, and change the mode of action of the second drug? These are practical issues that still do not have a definite answer. The real problem is that up to this moment no real biomarker is available to make the appropriate choice. The only clear-cut biomarker is represented by the positivity of rheumatoid factor (RF) or anti citrullinated peptide autoantibodies (ACPA). Seropositive patients seem to respond better than seronegative ones to B cell depletion therapy (Rituximab). This paper discusses the pros and cons of switching or swapping in RA patients poorly responder to the first TNFi.
22580587 Evaluating joint destruction in rheumatoid arthritis: is it necessary to radiograph both h 2013 Mar BACKGROUND: Radiological damage is an important outcome measure in rheumatoid arthritis (RA), both for research and clinical purposes. Depending on the setting, both hands and feet are radiographed, or only a part of these. It is unknown whether radiographing part of the four extremities gives comparable information to radiographing both hands and feet. This study therefore aimed to compare the radiological information obtained both when evaluating single time point radiographs and progression over time, in early and advanced RA. METHODS: 6261 sets of hands and feet x-rays of 2193 RA patients from Leiden, Groningen (both from The Netherlands) and North America were studied. Correlations between joint damage at different regions were compared (unilateral vs bilateral and hands vs feet). Analyses were done at single time points (cross-sectional) and for progression over time (longitudinal), both for continuous severity measures (Sharp/van der Heijde score; SHS) and binomial measures of erosiveness. RESULTS: When studying single time points, the severity of joint damage (SHS) is highly correlated between left and right, but weakly correlated between hands and feet. Correlation coefficients were higher in advanced than early RA. These findings were comparable in the three datasets. When evaluating erosiveness using only unilateral x-rays or hands without feet, 19.3% and 24.0-40.4% are incorrectly classified as non-erosiveness. Similarly, when evaluating disease progression by imaging only unilateral x-rays or only hand x-rays, progression would have been missed in 11.6-16.2% and 21.2-31.0% of patients. CONCLUSION: Performing x-rays of both hands and feet yields additive information compared with imaging only a part of these.
20931346 The effects of strength and endurance training in patients with rheumatoid arthritis. 2011 May Patients with rheumatoid arthritis (RA) suffer from muscle loss, causing reduced muscle strength and endurance. The current study aimed to: (1) evaluate the effects of combined strength and endurance training (CT) on disease activity and functional ability in patients with RA and (2) investigate the benefits of a 6-month supervised CT program on muscle strength, cardio-respiratory fitness, and body composition of RA patients. Forty patients with RA, aged 41-73 years, were recruited for the current study. Twenty of these patients (19 females, one male) were randomly assigned to a 6-month supervised CT program; 20 patients (17 females, three males) served as controls. Within the CT program, strength training consisted of sets of weight bearing exercises for all major muscle groups. In addition to strength training, systematic endurance training was performed on a cycle ergometer two times per week. For RA patients involved in CT, disease activity (p = 0.06) and pain (p = 0.05) were reduced after the 6-month training period while general health (p = 0.04) and functional ability (p = 0.06) improved. Cardio-respiratory endurance was found to have improved significantly (by 10%) after 6 months of CT (p < 0.001). The overall strength of patients undertaking CT increased by an average of 14%. Lean body mass increased, and the percentage of body fat was found to decrease significantly (p < 0.05). A combination of strength and endurance training resulted in considerable improvements in RA patients' muscle strength and cardio-respiratory endurance, accompanied by positive changes in body composition and functional ability. Long-term training appears to be effective in reducing disease activity and associated pain and was found to have no deleterious effects.
22924548 CCR5 gene polymorphism is a genetic risk factor for radiographic severity of rheumatoid ar 2012 Nov The chemokine receptor [C-C chemokine receptor 5 (CCR5)] is expressed on diverse immune effecter cells and has been implicated in the pathogenesis of rheumatoid arthritis (RA). This study sought to determine whether single-nucleotide polymorphisms (SNPs) in the CCR5 gene and their haplotypes were associated with susceptibility to and severity of RA. Three hundred fifty-seven patients with RA and 383 healthy unrelated controls were recruited. Using a pyrosequencing assay, we examined four polymorphisms -1118 CTAT(ins) (/del) (rs10577983), 303 A>G (rs1799987), 927 C>T (rs1800024), and 4838 G>T (rs1800874) of the CCR5 gene, which were distributed over the promoter region as well as the 5' and 3' untranslated regions. No significant difference in the genotype, allele, and haplotype frequencies of the four selected SNPs was observed between RA patients and controls. CCR5 polymorphisms of -1118 CTAT(del) (P = 0.012; corrected P = 0.048) and 303 A>G (P = 0.012; corrected P = 0.048) showed a significant association with radiographic severity in a recessive model, and, as a result of multivariate logistic regression analysis, were found to be an independent predictor of radiographic severity. When we separated the erosion score from the total Sharp score, the statistical significance of CCR5 polymorphisms showed an increase; -1118 CTAT(ins) (/del) (P = 0.007; corrected P = 0.028) and 303 A>G (P = 0.007; corrected P = 0.028). Neither SNPs nor haplotypes of the CCR5 gene showed a significant association with joint space narrowing score. These results indicate that genetic polymorphisms of CCR5 are an independent risk factor for radiographic severity denoted by modified Sharp score, particularly joint erosion in RA.
22064606 The safety and efficacy of etanercept on cardiac functions and lipid profile in patients w 2012 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) are known to be at increased cardiovascular risk. Etanercept is a tumor necrosis factor α (TNF-α) blocking agent that has been successfully used in the treatment of RA. We sought to assess the effects of etanercept on cardiac functions and lipid profile in RA patients without overt cardiac disease. METHODS: Sixteen patients with active RA were recruited to the study prospectively. Etanercept was administered subcutaneously twice a week for 6 months. Clinical and laboratory predictors of RA activity and lipid profile were evaluated at baseline and at 6 months. The systolic and diastolic function parameters of the left ventricle were obtained by echocardiographic examination and included mitral inflow Doppler and tissue Doppler imaging. RESULTS: Sixteen patients (13 women; median age, 48 years [range, 27-69 years]) completed the study. Patients' 28-item Disease Activity Score and Health Assessment Questionnaire scores were significantly reduced by treatment (6.35 to 4.45 [P < 0.001] and 2.0 to 0.75 [P = 0.005], respectively). Diastolic dysfunction was detected in 6 patients (37.5%) (3 in grade 1 and 3 in grade 2) by mitral inflow Doppler and the tissue Doppler parameters before the treatment. No significant change in diastolic dysfunction was observed during follow-up (6/16 to 5/16, P = 0.164). In addition, there were also no significant differences in the left ventricular ejection fraction (65.8-66.9, P = 0.168) and lipid profiles after 6 months of etanercept treatment. CONCLUSIONS: Etanercept treatment was safe for use as regards cardiac functions and lipid profiles and effective on RA parameters during 6-month follow-up in patients with active RA.
21816022 Decrease of CD68 and MMP-3 expression in synovium by treatment of adalimumab for rheumatoi 2011 Aug AIMS: In order to investigate the histological change in the secondary non-responder cases of adalimumab compared with methotrexate (MTX) treatment, we performed immunohistochemical examination of synovial tissue by seven different molecules to detect expression patterns of cytokines. METHODS: We histologically assessed synovial tissues from five MTX-treated rheumatoid arthritis (RA) patients as controls and five adalimumab plus MTX-treated RA patients after arthroscopic synovectomy in the knee joints. The synovium of both groups were assessed by hematoxylin and eosin (H&E) and analyzed the positive expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), B-cell precursor and mature B-cell transmembrane protein, CD20, macrophage marker, CD68, vascular endothelial growth factor (VEGF), receptor activator of nuclear (kappa) B ligand (RANKL) by immunohistochemical examination. RESULTS: H&E staining showed the increase of vascular and cell proliferations in the synovium of the RA patients who received adalimumab compared with the controls. TNF-α, IL-6 and CD20 were not significantly different in either group. On the other hand, MMP-3 and CD68 showed a significant decrease in the adalimumab group compared with controls (P < 0.05). VEGF and RANKL were weakly positive in both groups. CONCLUSION: Based on the histological analysis of synovium, the effect attenuation of adalimumab may be involved in vascular and cell proliferations; however, there was inhibition of the expression of CD68 and MMP-3 in synovium. These findings indicate CD68 and MMP-3 may have key roles in the mechanism of efficacy of adalimumab.
21418779 Signal transducer and activator of transcription and the risk of rheumatoid arthritis and 2011 Mar OBJECTIVES: The signal transducer and activator of transcription 4 (STAT4) gene localised on chromosome 2q32.2-q32.3 is known to be essential for mediating responses to interleukin 12 in lymphocytes and regulating the differentiation of T helper cells. The aim of this study was to investigate the role of the STAT4 gene in susceptibility to rheumatoid arthritis (RA) and autoimmune thyroid diseases (AITDs) in Tunisian case control studies. METHODS: Genotyping of STAT4 rs7574865 single nucleotide polymorphism (SNP) was performed in 140 patients affected with RA, 159 patients affected with AITDs and 200 healthy controls using TaqMan® allelic discrimination assay. Data were analysed by χ2-test, genotype relative risk (GRR) and odds ratio (OR). RESULTS: Our results revealed that frequencies of the T allele and the T/T genotype were significantly higher among RA patients compared to controls (p=0.008; p=0.003, respectively). However, no significant associations with the risk of autoimmune thyroid diseases were detected. Moreover, the stratification of RA patients subgroups revealed a significant association of both T allele and T/T genotype in patients presented erosion (p=0.003; p=0.004, respectively) as well as anti-cyclic peptides-negative RA (ACPA-) (p=0.002; p=0.0003, respectively). Furthermore, genotypic association was found according to the absence of rheumatoid factor antibody (RF) (p=0.0014). But, no significant differences in allele and genotype frequencies of STAT4 rs7574865 polymorphism were detected according to the presence of another autoimmune disease, nodules and in HLA-DRB1*04 and HLA-DRB1*0404 positive subgroups. CONCLUSIONS: Our results support involvement of the STAT4 gene in the genetic susceptibility to RA but not to AITDs in the Tunisian population.
22052599 Effectiveness of a clinical practice intervention in early rheumatoid arthritis. 2012 Mar OBJECTIVE: To compare the outcome of early rheumatoid arthritis (RA) patients in a country where early clinics were established versus the outcome of patients in nonprotocolized clinics. METHODS: We compared 2 multicenter cohorts: an RA cohort derived from an early arthritis registry set in 36 reference hospitals in which a specific intervention was established (Evaluation of a Model for Arthritis Care in Spain [SERAP]), and a historical control cohort of patients with early RA attending 34 rheumatology departments (Prognosis in Rheumatoid Arthritis [PROAR] cohort). Effectiveness was tested by comparing the change in the Disease Activity Score in 28 joints (DAS28), the change in the Health Assessment Questionnaire (HAQ), and the change in the Sharp/van der Heijde radiologic score using marginal structural models. RESULTS: A total of 161 early RA patients were recruited in the PROAR cohort and 447 in the SERAP cohort. Being a SERAP patient was inversely correlated with activity, resulting in a decrease of -0.24 (95% confidence interval [95% CI] -0.39, -0.08) units in the population average of the DAS28 after adjustment was made. Moreover, intervention may be seen as a protective factor of radiologic damage, with a decrease of -0.05 (95% CI -0.09, -0.01) units in the logarithm of the total Sharp/van der Heijde score. On the other hand, a decrease in functional impairment was detected, but intervention was not statistically associated with HAQ changes. CONCLUSION: Preventing major radiographic progression in a 2-year term inside structured and organized special programs for the management of disease, such as early arthritis clinics, are effective compared to nonprotocolized referrals, treatment, and followup.
22797111 Immunomodulatory effect of sertraline in a rat model of rheumatoid arthritis. 2012 OBJECTIVE: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) modulate immune system functionality. SSRIs are the preferred treatment for major depressive disorder (MDD). A high rate of MDD is observed in rheumatoid arthritis (RA) patients. The aim of this study was to evaluate immunological effects of SSRIs in a rat model of RA. METHODS: Adjuvant arthritis was induced in 8-week-old Lewis rats; in the first set of experiments following the induction, 15.3 or 30.6 mg/kg of sertraline was daily injected into the ankle joint of the left rear leg. Clinical disease activity was evaluated and the findings compared with the 3 untreated legs and with control groups given methotrexate (MTX) or vehicle only at the same site. In a second set of experiments, the effect of 5, 25 and 50 mg/kg daily oral sertraline was evaluated in the same rat model. Splenocyte viability and inflammatory mediators were evaluated. RESULTS: The sertraline-treated rats showed a significant reduction in clinical arthritis compared to controls, at all doses given, accompanied by a significant increase in interleukin 10 and a decrease in tumor necrosis factor-α levels and cycloxygenase-2 production, without lymphotoxicity. There was no significant difference from MTX, the first-line treatment for RA patients. Oral sertraline had a significant anti-inflammatory effect at all doses. There was no treatment × time effect. CONCLUSION: The beneficial effects of sertraline in this rat model of arthritis have clinical implications for its use in humans. Large-scale clinical efficacy trials are needed.
21331575 Increased myeloperoxidase plasma levels in rheumatoid arthritis. 2012 Jun High myeloperoxidase (MPO) serum levels have been shown in several inflammatory diseases, including rheumatoid arthritis (RA). However, the correlation between MPO levels and disease activity in RA patients is still controversial. The aim of the study was to determine MPO plasma levels in RA patients and to investigate potential correlations between MPO levels and disease activity and treatment. MPO plasma levels were measured by ELISA according the manufacturer's instructions. Disease activity was measured by DAS28 ESR and DAS28 CRP scores, and patients were classified into 4 groups: group 1 DAS28 < 2.6; group 2: 2.6 ≤ DAS28 ≤ 3.2; group 3: 3.2 < DAS28 ≤ 5.1 and group 4: DAS28 > 5.1. Rheumatoid factor (RF) was measured by latex agglutination test, and anti-cyclic citrullinated peptide (anti-CCP) antibodies were detected by ELISA with a commercial kit. Fifty-seven female RA patients (mean age: 46.02 ± 13.47 years, mean disease duration: 115.77 ± 99.44 months) and sixty gender- and age-paired healthy controls were included. Mean MPO plasma levels were significantly higher in patients than in controls (72.27 pM vs. 40.78 pM, P = 0.007). RF was found in 59.6% and anti-CCP in 80.7% of the RA patients. No significant difference in MPO levels was seen among the four RA disease activity groups. We did not find significant correlation between MPO levels and disease activity as measured by DAS28 score. In conclusion, we observed significantly higher MPO plasma levels in RA patients when compared to healthy controls. However, we did not find correlation between MPO plasma level and disease activity.