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ID PMID Title PublicationDate abstract
23217276 Citrullinated fibronectin inhibits apoptosis and promotes the secretion of pro-inflammator 2012 Dec 10 INTRODUCTION: Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLSs). Antibodies against citrullinated proteins are proposed to induce RA. This study aimed to investigate the pathogenic role of citrullinated fibronectin (cFn) in RA. METHODS: The distribution of fibronectin (Fn) and cFn in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical and double immunofluorescence analysis. FLSs were isolated from RA and OA patients and treated with Fn or cFn. Apoptosis was detected by flow cytometry and TUNEL assay. The expression of survivin, caspase-3, cyclin-B1, Bcl-2 and Bax was detected by real-time PCR. The secretion of proinflammatory cytokines was measured by ELISA. RESULTS: Fn formed extracellular aggregates that were specifically citrullinated in synovial tissues of RA patients, but no Fn deposits were observed in those of OA patients. Fn induced the apoptosis of RA and OA FLSs while cFn inhibited the apoptosis of RA and OA FLSs. Fn significantly increased the expression of caspase-3 and decreased the expression of survivin and cyclin-B1 in FLSs from RA and OA patients. cFn significantly increased the expression of survivin in RA FLSs. Furthermore, cFn increased the secretion of TNF-α and IL-1 by FLSs. CONCLUSIONS: cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs.
22325985 Attending and non-attending patients in a real-life setting of an early arthritis clinic: 2012 Mar OBJECTIVES: Rheumatologist assessment as early as possible is considered essential for patients with inflammatory joint disease. In our Very Early Arthritis Clinic (VEAC), a substantial proportion of initially included and followed patients later stop attendance in the clinic. We questioned attending (AP) and non-attending patients (NAP) regarding current health status and satisfaction with care as well as reasons for discontinuation and current care received by NAP. METHODS: VEAC patients first seen between 1996 and 2003 were included. Assessment included the RADAI, HAQ, and visual analogue scales for pain, disease activity, fatigue, satisfaction with current health care. Current (DMARD) treatment was recorded. RESULTS: Among AP, 87% had rheumatoid arthritis (RA) and 13% non-RA. Of NAP, 37% had RA, 23% non-RA and 40% no more rheumatic disease. Satisfaction with health care concerning rheumatic disease was better in AP than NAP. Likewise, most outcome parameters were better in AP. Substantially more RA patients in the AP than NAP group received DMARDs. Apart from the disappearance of arthritis, logistic reasons were given most frequently for discontinuation of attendance. Less than 10% of NAP indicated dissatisfaction with medical care. CONCLUSIONS: We found advantages in both disease activity measures and satisfaction with health care for patients receiving continuous care in a highly specialised Rheumatology clinic. Furthermore, different DMARD usage in RA in AP and NAP may indicate significant deficits in treatment quality outside specialist care. Logistic issues associated with access to continuous Rheumatology care for early arthritis patients need improvement.
22018187 A dose of only 5 mg prednisolone daily retards radiographic progression in early rheumatoi 2011 Sep Glucocorticoids (GC) have been used to treat rheumatoid arthritis (RA) for more than 60 years. Despite this very long experience, there remains considerable debate concerning the adequate dosing and timing of these medications, primarily because of frequent and sometimes serious side effects, particularly in high doses. GCs are documented to provide immediate symptomatic relief and to decrease signs of inflammation in active disease. At the time when the Low-Dose Prednisolone Trial (LDPT) was designed, no clear evidence was available concerning whether low doses of GCs given over a long period add to slowing of structural damage in RA. The trial was therefore designed to test the hypothesis that even a low dose of prednisolone that was thought to cause no or only very limited harm could slow radiographic progression. The trial therefore included patients with active early RA (disease duration less than two years) who received either prednisolone 5 mg/day or placebo on concomitant DMARD therapy with parenteral gold or methotrexate for two years. Radiographs of hands and feet were taken at baseline, and at 6, 12 and 24 months. Structural damage was assessed using change in the Ratingen score (0-190 scale) as the primary outcome, and change in the Sharp/van der Heijde score (0-448 scale) for additional information concerning the same radiographs. Of 192 patients in the study, 166 were available for intention to treat analysis (ITT), and 76 completed the study per protocol (PP). Progression of the Ratingen score was significantly less at all consecutive time points in the prednisolone group compared to the control group, with the greatest difference after 6 months. At 24 months the increase in score in the prednisolone group was 1.2 ± 3.5, (95% CI 0.4-2.1) and in the placebo group 4.3 ± 6.8 (95% CI 2.7-5.9) (p=0.006, ITT-analysis). This was confirmed by the results of the Sharp/van der Heijde erosion and total score with an increase of the total score of 5.3 ± 10.7 units in the prednisolone compared to 11.4 ± 19.1 in the placebo group (p=0.022) at 24 months. The LDPT trial therefore confirmed that a very low daily dose of 5 mg prednisolone given over two years in combination with background DMARD therapy substantially decreases radiographically detectable damage in patients with early RA.
21126560 Tripterygium wilfordii Hook F. versus Sulfasalazine in the treatment of rheumatoid arthrit 2011 Jan Claims that Traditional/Alternative medicine (TM/AM) remedies are effective are routinely ignored by Western Medicine. However, the results of a clinical trial that demonstrated the clinical efficacy of Tripterygium wilfordii Hook F. (TW), a TM used as an anti-inflammatory, were recently published in the Annals of Internal Medicine. Why this article was published in a peer reviewed Allopathic medical journal is an important question that begs examination and may lay the future promise of TM/AM therapeutic interventions.
21479604 CIP2A expression is associated with synovial hyperplasia and invasive function of fibrobla 2012 Jul Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.
20661738 Plasma soluble IL-6 receptor concentration in rheumatoid arthritis: associations with the 2011 Mar Soluble interleukin-6 receptor α subunit (sIL-6R) is primarily generated by shedding of the membrane-bound form. This process is influenced by the single nucleotide polymorphism rs8192284 (A > C) resulting in an aspartic acid to alanine substitution (D358A) at the proteolytic cleavage site. The aim of this study was to determine whether plasma levels of sIL6R are influenced by the rs8192284 polymorphism in patients with rheumatoid arthritis and to assess the association between plasma sIL-6R levels and disease activity as reflected by anti-CCP status. Thirty-nine patients were randomly selected from a cohort of patients with RA of Spanish descent. Plasma sIL-6R concentrations were measured using sandwich ELISA. Genotyping of the rs8192284 (A > C) polymorphism was done using a Fast Real-Time PCR System. DAS 28 scores were used to assess disease activity. Plasma sIL-6R levels were positively associated with the number of C alleles (AA: 35.27 (3.50) ng/ml, AC: 45.50 (4.58) ng/ml, CC: 52.55 (3.18) ng/ml, P = 0.0001). DAS28 and plasma sIL-6R levels were positively associated in the anti-CCP-positive subgroup (r (2) = 0.45, P = 0.0336) and negatively associated in the anti-CCP-negative subgroup (r (2) = -0.45, P = 0.0825). No association between anti-CCP status and sIL-6R level was found. Our findings show that the rs8192284 polymorphism is operative in patients with RA. The presence of anti-CCP antibodies determines the relationship between sIL-6R concentration and disease activity.
21412604 Potential drug interactions in patients with rheumatoid arthritis. 2011 Jan INTRODUCTION: The term polypharmacy, meaning the concomitant use of multiple medications by one individual, has been widely reported in institutionalized or elderly patients. It can, however, occur in patients with chronic diseases, such as rheumatoid arthritis (RA). OBJECTIVE: To quantify polypharmacy in a group of RA patients and to assess the risk of potential undesirable interactions between medications used for managing RA and those used for non-chronic diseases. METHODS: A cohort study was carried out with 103 RA patients registered at the Strategy of Access to Medications from the Brazilian Health Ministry, at the School of Pharmacy of the city of Florianópolis, state of Santa Catarina. Patients were monthly followed up by use of form completion. Drug interactions were identified by use of the Drugdex System - Thomson Micromedex® - Interactions database. RESULTS: Polypharmacy was found in 95.1% of the patients, and 19 potential undesirable interactions were observed between the drugs used by 74 patients (mean of 3.0 ± 1.2 interactions/patient). All potential interactions were related to methotrexate. Omeprazole was the major representative, accounting for 29.3% of the interactions, followed by diclofenac sodium (17.6%), and metamizole sodium (13.2%). CONCLUSION: Considering that this study confirms that polypharmacy is a common therapeutic practice in RA patients, it is worth emphasizing the need for greater surveillance regarding the adverse effects or effectiveness reduction of certain drugs due to drug interaction.
23157277 Is inclusion of the occiput necessary in fusion for C1-2 instability in rheumatoid arthrit 2013 Jan OBJECT: The atlantoaxial joint is the location most and earliest affected in patients with rheumatoid arthritis (RA). In longstanding disease, ligamentous and osseous destruction can progress and involve all cervical segments. If surgical intervention is necessary, some prefer, to be safe, undertaking fusion to the occiput, whereas others advocate 1-level fusion of C1-2. Sparing the occiput (Oc)-C1 segment would allow retention of a considerable amount of physiological range of motion and seems beneficial against subaxial overload. Previous clinical studies on this topic have provided only nonspecific data after short-term follow-up, rendering a segment-sparing approach questionable. The purpose of the present investigation was to assess long-term progression of inflammatory or degenerative destruction in the Oc-C1 segment after isolated C1-2 fusion for RA. METHODS: In a series of 113 consecutive patients with RA-related destruction restricted to the craniocervical junction, 14 individuals underwent Oc-C2 fusion and 99 underwent surgery exclusively at the C1-2 level. After a mean follow-up period of 9.4 years (range 4.9-14.7 years), 46 patients were available for clinical and radiographic examination, including CT imaging. RESULTS: None of the 46 patients needed additional surgery to extend the fusion to the occiput. Despite marked deterioration in the subaxial cervical spine, in general there were little or no changes in the atlantooccipital region. All but one patient presented with bony fusion of the fixed C1-2 level at follow-up. CONCLUSIONS: The results of this investigation suggest that if the Oc-C1 joint is free of osseous destructions on conventional radiographs and free of abnormalities on MRI scans at the time of surgery (for transarticular fixation and fusion of C1-2), there is a very low risk for relevant destruction in the following 5-14 years. Thus, no prophylactic oligosegmental approach, but rather a segment-sparing monosegmental approach, is preferred, even in patients with high inflammatory levels.
22915531 Carotid artery intima-media thickness and brachial artery flow-mediated vasodilatation in 2012 Sep BACKGROUND: Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Our study aim was to determine the relationship between carotid artery intima-media wall thickness (IMT) and flow-mediated endothelium-dependent vasodilatation (FMD) in a patients with RA, in context with clinical and laboratory measurements. PATIENTS AND METHODS: Fifty-two patients with RA and 30 matched healthy controls without clinically evident CV disease were studied. Brachial and carotid ultrasonography was performed to determine FMD and IMT, respectively. We also assayed immunological, inflammatory and metabolic laboratory markers. RESULTS: IMT was significantly higher in RA patients (1.00 ± 0.16 mm) patients than in controls (0.89 ± 0.13 mm) (P = 0.001). FMD was significantly lower in RA (9.16 ± 7.03) as compared to controls (12.60 ± 5.49) (p = 0.005). RA patients had significant positive correlations between erythrocyte sedimentation rate (ESR) (r=0.395 p = 0.021) and IMT and negative correlation between visual analog scale (VAS) (r= -0.311, p= 0.025) and IMT. RA patients who used low doses of corticosteroids have, statistically, significantly better FMD, than those who do not use corticosteroids. Linear regression analysis revealed that IMT was related to tender joint count (p = 0.008), VAS (p < 0.001), ESR (p = 0.048) and total cholesterol/high density lipoprotein cholesterol ratio (p = 0.039). CONCLUSIONS: In patients with RA, FMD was impaired and IMT was increased, indicating early endothelial dysfunction and accelerated atherosclerosis. Early treatment of disease may reduce the risk of atherosclerosis in RA.
22349908 Quantification of periarticular demineralization and synovialitis of the hand in rheumatoi 2012 Nov The bone mineral density (BMD) measurement of the hand in rheumatoid arthritis (RA) patients is no standard measurement method as yet. The aim was to contribute to the standardization of the hand BMD measurement, especially of periarticular regions. As results, we found best precision values for the wrist and a significant correlation between hand and spine/femur BMD depending on disease activity and disease duration. INTRODUCTION: This study was conducted to investigate (i) the precision of periarticular hand BMD measuring, (ii) the periarticular demineralization of the hand, (iii) the correlation between periarticular hand BMD and spine/femur BMD, and (iv) the correlation of hand BMD to hand synovitis. METHODS: A number of 52 RA patients were examined by BMD measurement of the femoral neck, spine, whole hand, metacarpophalangeal (MCP) joints II-V, personal identity profile (PIP) joints II-V, and wrist using dual-energy X-ray absorptiometry (DXA). Synovitis of the hand was examined by ultrasonography and magnetic resonance imaging (MRI). Three subgroups were further analyzed: early RA, established RA with moderate and with high disease activity. Early RA and established RA patients with high disease activity were Followed up after 12 months. RESULTS: We found (1) best precision of BMD measurement for the wrist, (2) BMD in RA significantly reduced if compared to normal controls, (3) a highly significant positive correlation between hand and spine/femur BMD and the power of correlation to depend on disease activity and disease duration (high correlation in RA with moderate disease activity and early RA, very high correlation in RA with high disease activity), (4) a negative correlation between hand BMD and hand synovitis in RA with high disease activity, and (5) a significant reduction of synovitis but no change in hand BMD after 12 months, respectively. CONCLUSIONS: This study shows a highly significant correlation between hand BMD and spine/femur BMD in RA patients depending on disease activity and disease duration. We conclude to measure BMD at different sites including hands in order to quantify bone loss in RA patients most properly.
23053717 Preferences of Japanese rheumatoid arthritis patients in treatment decision-making. 2013 Sep OBJECTIVES: We investigated the decision-making preferences of rheumatoid arthritis (RA) patients using two different scales: the Decision Making Preference Scale (DMPS) and the modified Control Preference Scale (CPS). In addition, we evaluated the factors associated with patients' preferences for decision-making. METHODS: A cross-sectional study was performed using a self-administered anonymous questionnaire between October and December 2010 on 406 RA outpatients who consecutively visited 3 hospitals in Japan. The following variables were investigated: (1) DMPS, which is a subscale of the Autonomy Preference Index, composed of six items; patients responded on a 5-point Likert scale. (2) The modified CPS, in which patients were asked to choose one actual and one desired role in decision-making from among three options (passive role, collaborative role, and active role). (3) Sociodemographic data and RA-specific characteristics. Multivariate analyses were used to assess the relationship between patients' preferences and selected variables. RESULTS: The response rate was 58.6 %. There were few patients who wished to make their own decisions when they were hospitalized or illness became worse. However, the majority of patients desired to collaborate with the doctor in making treatment decisions according to the results of modified CPS. The results of modified CPS were significantly associated with the total scores of DMPS. Multivariate analysis demonstrated they younger age and not-housewife were associated with high scores of DMPS. CONCLUSIONS: Patient preferences in decision-making vary at RA outpatient clinic. Physicians need to assess decision-making preferences on an individual basis.
21502696 [The importance of pharmacogenetic tests in evaluation of the effectiveness of methotrexat 2011 Mar 30 Methotrexate (MTX) is still the gold standard in the treatment of rheumatoid arthritis and is used worldwide in more than 0.5 million patients with RA. Much hope is currently associated with the individualization of therapy provided to RA patients. The search is underway for biochemical and clinical markers that would be useful in predicting good response to MTX therapy. Along with clinical factors, genetic predisposition may also be helpful. Polymorphism of genes participating in MTX metabolism may affect the drug’s efficacy and the rate of adverse effects. Pharmacogenetic studies may contribute to more effective individualization of therapy for RA patients. There are many potential enzymes and transport proteins present in polymorphic forms, which are involved in transport of MTX into the cell, its metabolism and elimination from the cell. There is a chance that in the future through individualized therapy we will be able to customize therapy (type of drug, dose, route of administration) to the molecular subtype of the disease and the genotype of the patient. Patients with a specific type of polymorphism would require more frequent monitoring of the efficacy and safety of treatment. Note, however, that genetic predisposition is only one of the factors contributing to differences in pharmacotherapy in individual patients.
22531887 Relation of interleukin-6 in rheumatoid arthritis patients to systemic bone loss and struc 2013 Mar IL-6 plays a key role in local and systemic manifestation of RA. IL-6 is not only a pro-inflammatory cytokine, but also interacts in complex ways with the cells involved in bone remodeling. In RA, IL-6 may indirectly promote osteoclastogenesis by increasing the release of RANK-L by osteoblasts, and it diminishes the proliferation of osteoblasts at late differentiation stages. The aims of this work were to evaluate the level of serum IL-6 and to correlate it with the activity, severity, early development of osteoporosis, and early structural bone damage in RA patients. The following parameters were investigated in 40 RA patients and 20 healthy controls: IL-6 level, BMI, ESR, CRP, CBCs, serum ionized calcium, blood urea, serum creatinine, AST, ALT, anti-CCP, and RF. Bone mineral density was measured by dual-energy X-ray absorptiometry at lumbar spines and femoral neck. Drug history was taken stressing on steroid therapy. Data were processed and analyzed using computer-based program. IL-6 was significantly positively correlated with HAQ1, PTGA, grade of pain, ESR, platelet count, blood urea, AST level, and anti-CCP level; IL-6 showed an inverse significant correlation with T-score. IL-6 was positively correlated with TGC, DAS-28 score, and RF level. No correlation was found between T-score and morning stiffness duration, BMI, CRP, RBC, serum creatinine, and ALT. There was an inverse significant correlation between T-score and HAQ1, SJC, pain grade, DAS-28 score, PTGA, ESR, RF, anti-CCP, and IL-6. Patients with RA on steroid therapy had significantly higher TJC, SJC, and DAS-28 score, anti-CCP, and IL-6 than patients with RA not on steroid therapy. Patients with RA on steroid therapy had significantly lower T-score and lower serum ionized calcium than patients with RA not on steroid therapy. IL-6 has an important role in increasing osteoclastic activity and subsequent bone resorption in the patients with RA. Blocking IL-6 by using IL-6 inhibitors and anti-RANK-L therapy may be effective in inhibiting the inflammatory process and preventing the bone complications of RA disease.
21415022 Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthriti 2011 Aug OBJECTIVE: To determine the incidence of and risk factors for non-melanoma skin cancer (NMSC) in a national cohort of veterans with RA. METHODS: We examined skin cancer risk in a cohort of 20 648 patients with RA derived from the Department of Veterans' Affairs (VA) national administrative databases. The cohort was divided into two medication groups: patients treated with non-biologic and TNF-α antagonist DMARDs. We defined skin cancer as the first occurrence of an International Classification of Disease, Version 9, Clinical Modification (ICD-9-CM) code for NMSC after initiation of a DMARD. Outcome risk was described using hazard ratios (HRs) with Cox proportional hazards regression for time-to-event analysis and logistic regression. We performed medical record review to validate the diagnosis of NMSC. RESULTS: Incidence of NMSC was 18.9 and 12.7 per 1000 patient-years in patients on TNF-α antagonists and non-biologic DMARDs, respectively. Patients on TNF-α antagonists had a higher risk of developing NMSC (HR 1.42; 95% CI 1.24, 1.63). Risk factors for NMSC included older age, male gender, NSAID and glucocorticoid use and a history of prior malignancies. There was substantial agreement between ICD-9-CM diagnosis of NMSC and medical record validation (κ = 0.61). CONCLUSION: TNF-α antagonist therapy in veterans with RA may be associated with an increased risk of NMSC, compared with therapy with non-biologic DMARDs. Rheumatologists should carefully screen patients receiving TNF-α antagonists for pre-cancerous skin lesions and skin cancer.
20726683 Trends in treatment strategies and the usage of different disease-modifying anti-rheumatic 2011 Jan OBJECTIVES: To determine which disease-modifying anti-rheumatic drugs (DMARDs) are currently used by Finnish rheumatologists to treat early rheumatoid arthritis (RA). METHODS: Information on sex, date of birth, and date of special medicine reimbursement decision for all new RA patients was collected from a nationwide register maintained by the Social Insurance Institution (SII) during the time period from 1 January 2000 to 31 December 2007. Patient cohorts were registered in 2-year time periods (2000-01, 2002-03, 2004-05, 2006-07) and DMARDs purchased by the patient cohorts during the first year after the date of reimbursement decision for RA were registered. The frequencies of early drug treatment strategies (combination of DMARDs, single DMARD, or no DMARDs) were evaluated. RESULTS: A total of 14 878 (68.0% female, 62.6% rheumatoid factor (RF)-positive) patients were identified. Between 2000 and 2001 the most commonly used treatment strategy for early RA during the first 3 months was single DMARD treatment (56.1%) and the most commonly used DMARD during the first year was sulfasalazine (63.0%), while between 2006 and 2007 the respective treatments were combination DMARDs (55.3%) and methotrexate (69.0%). The change in treatment strategies as well as in DMARDs used was highly significant (p < 0.001 for linearity). At the end of the study period only 4.9% of the patients with early RA were not receiving DMARDs during the first 3 months. CONCLUSIONS: Currently, combination therapy including methotrexate is the most commonly prescribed treatment strategy for early RA in Finland. In recent years, an increasing number of active drug treatments have been taken into practice.
22829690 Peroxisome proliferator-activated receptor-gamma expression in monocytes/macrophages from 2012 Nov OBJECTIVES: Peroxisome proliferator-activated receptor-gamma (PPARγ) is expressed by different cell types in the joints and plays a relevant anti-inflammatory role in various diseases. This pilot study aimed to evaluate PPARγ expression in monocytes/macrophages isolated from RA patients as compared with healthy subjects, the relationships between PPARγ expression, MMP-9 activity and disease, and the influence of therapy with anti-rheumatic drugs on these parameters. METHODS: Thirty RA patients of both sexes (treated with CSs and MTX, mainly) and 15 healthy volunteers were enrolled in this study. Disease severity was evaluated by the 28-joint disease activity score (DAS-28). Monocytes and monocyte-derived macrophages (MDMs) were isolated by standard procedures. PPARγ protein and mRNA expression were assessed by immunoblotting and real-time PCR, respectively; MMP-9 activity was determined by gelatin zymography. Moreover, we checked the ability of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ, a PPARγ agonist), MTX and methylprednisolone (MP) to affect PPARγ expression and lipopolysaccharide (LPS)-induced MMP-9 activity. RESULTS: Monocytes/MDMs from RA patients have significantly enhanced PPARγ expression (both protein and mRNA) and MMP-9 activity as compared with healthy donors. Interestingly, cells from patients with less active disease (DAS-28 <3.2) present higher PPARγ protein expression and lower MMP-9 activity than RA patients with DAS-28 >3.2. At therapeutic concentrations, MTX and MP increase in vitro PPARγ protein expression and inhibit LPS-induced MMP-9 activity. CONCLUSION: PPARγ expression in human monocytes/MDMs could represent an indicator of disease activity and therapy efficacy in RA because patients with a DAS-28 score <3.2 show the highest expression.
22120463 Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized cont 2012 Mar OBJECTIVE: To evaluate the efficacy of resistance exercises in RA patients. METHODS: A systematic literature search was done using Pubmed, Embase and Cochrane databases through November 2009 and in abstracts presented at rheumatology scientific meetings over the past 3 years. Randomized controlled trials (RCTs) comparing resistance exercise based therapy with interventions without resistance exercise for the treatment of RA patients were included. Outcomes studied were post-intervention disability on the HAQ, functional capacity assessed by walking speed, pain on the visual analogue scale (VAS), joint count, isometric, isokinetic and grip strength. Efficacy was assessed by weighted mean differences (WMDs) and tolerance was assessed by relative risk (RR). Data were pooled using the inverse of variance model, and heterogeneity was tested. RESULTS: Ten RCTs, including 547 patients, met the study inclusion criteria. The mean (S.D.) Jadad score was 2.3 (0.6). Resistance exercises significantly improved isokinetic strength (WMD = 23.7%, P < 0.001), isometric strength (WMD = 35.8%, P < 0.001), grip strength (WMD = 26.4%, P < 0.001) and HAQ (WMD = -0.22, P < 0.001). Exercise also had a positive impact on the 50-foot walking test (WMD = -1.90 s, P < 0.001) and ESR (WMD = -5.17, P = 0.005). Withdrawals [RR = 0.95, 95% confidence interval (CI) 0.61, 1.48] and adverse events (RR = 1.08, 95% CI 0.72, 1.63) were well balanced in both groups. Patient and exercise characteristics did not influence the results. Subgroup analysis revealed a trend towards higher efficacy associated with high-intensity programmes. CONCLUSION: Resistance exercise in RA is safe, and the improvement in most outcomes was statistically significant and possibly clinically relevant for RA disability.
23125866 TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with prima 2012 BACKGROUND: Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an autoimmune liver disease which can co-exist with RA, is unknown. AIM OF THE STUDY: To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with clinical features and autoantibody markers was also analyzed. METHODS: We studied 179 PBC patients and 300 controls. Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR. Autoantibodies were tested by ELISA. RESULTS: The frequency of rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. Laboratory or clinical features were not associated with specific polymorphisms. Gp210 autoantibody titres were conspicuously higher among GG homozygotes of rs3761847 as compared with AA homozygotes (P = 0.02). In contrast, antichromatin titers were higher in AA compared to GG rs3761847 homozygotes (P = 0.04). Rheumatoid factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC homozygotes (P = 0.02). CONCLUSIONS: TRAF1 polymorphisms occur with the similar frequency in PBC patients and in the general population, but their presence is probably involved in the regulation of specific PBC-related autoantibodies.
22424189 The role of environmental factors in the pathogenesis of non-organ-specific autoimmune dis 2012 Feb The immune system must be able to discriminate between self and non-self. However, mechanisms of doing so sometimes fail, causing the activation and clonal expansion of autoreactive lymphocytes and the development of autoimmune conditions. Although some autoimmune diseases have heritable components, these components are not sufficient to develop an autoimmune condition. A variety of environmental factors have been described as possible triggers of autoimmune diseases, including drugs, infectious agents, smoking, vaccination and adjuvants. The aim of this chapter is to review the most common environmental factors associated with autoimmune diseases.
22704962 Rheumatoid arthritis: from autoimmunity to synovitis and joint destruction. 2012 Sep Rheumatoid arthritis is an autoimmune disease characterized by the production of two known antibodies - rheumatoid factor and anti-citrullinated peptide antibody (ACPA) - against common autoantigens that are widely expressed within and outside the joints. The interactions between genes and environment are crucial in all stages of the disease, involving namely genes from major histocompatibility complex locus, and antigens such as tobacco or microbes (e.g. Porphyromonas gingivalis). T and B cells are activated as soon as the earliest phases of the disease, rheumatoid arthritis appearing as a Th1 and Th17 disease. Inflammatory cytokines have a considerable importance in the hierarchy of the processes involved in RA. The joint destruction seen in RA is caused not only by cytokine imbalances, but also by specific effects of the Wnt system and osteoprotegerin on osteoclasts and by matrix production dysregulation responsible for cartilage damage. Both innate and adaptative immunity demonstrated their respective cornerstone position in rheumatoid arthritis, since targeted treatments has been efficiently developed against TNF-α, IL-6 receptor, IL-1β, CD20 B cells and T-cell/Dendritic cell interactions.