Browse

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

ID PMID Title PublicationDate abstract
20205741 Exploring Tai Chi in rheumatoid arthritis: a quantitative and qualitative study. 2010 Mar 5 BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and systemic disease which affects the musculoskeletal system. Exercise programmes are reported to improve physical functioning in patients with RA. Tai Chi is a traditional Chinese martial art which combines slow and gentle movements with mental focus. The purpose of this study was to study in which way Tai Chi group exercise impacted on disease activity, physical function, health status and experience in RA patients, applying quantitative and qualitative methods. METHODS: Fifteen patients with RA (13 females, age 33-70 years) were recruited from a rheumatology department into a single group study. The patients were instructed in Tai Chi exercise twice weekly for 12 weeks. Assessments at baseline, 12 weeks, and 12 weeks follow-up were performed with a wide range of measures, including disease activity, self-reported health status, physical performance tests (Walking in Figure of Eight, Timed-Stands Test, and Shoulder Movement Impairment Scale). Qualitative data were obtained from a focus group interview conducted after completed intervention with taping and verbatim transcription. Review of the transcripts identified themes important to patients practicing Tai Chi. RESULTS: Within the group, Tai Chi practice lead to improved lower-limb muscle function at the end of intervention and at 12 weeks follow-up. Qualitative analyses showed that patients experienced improved physical condition, confidence in moving, balance and less pain during exercise and in daily life. Other experience included stress reduction, increased body awareness, confidence in moving and indicated that Tai Chi was a feasible exercise modality in RA. CONCLUSIONS: Improved muscle function in lower limbs was also reflected when patient experiences with Tai Chi were studied in depth in this explorative study. The combination of qualitative and quantitative research methods shows that Tai Chi has beneficial effects on health not related to disease activity and standardised health status assessment, and may contribute to an understanding of how Tai Chi exerts its effects. TRIAL REGISTRATION: NCT00522054.
19450146 Circulating levels of interferon-gamma in course of hepatitis C virus-related arthritis. 2009 Jul The aim was to weigh the serum concentrations of interferon gamma (IFN-gamma), a cytokine that enhances Th1-cell differentiation and suppresses collagen synthesis and angiogenesis, in two apparently distinct diseases, hepatitis C virus-related arthritis (HCVrA) and rheumatoid arthritis (RA), which share some overlapping immunological features. In this study, IFN-gamma serum levels were assayed by an ELISA method in 21 HCVrA patients and in 16 with RA. Very low IFN-gamma serum levels were found in five out of 21 patients with HCVrA and only in three out of 16 RA patients. Median value (range) resulted decrease in both HCVrA and RA groups, that is, 0.29 (0.04-1.49) versus 0.20 (0.05-1.18) IU/mL, P = 0.58. No correlation was evidenced with hepatic and arthritic involvements, nor between IFN-gamma serum levels and viral replication and moreover with the positivity of antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated peptides antibodies. These results show that IFN-gamma behavior appears similar in HCVrA and RA groups reinforcing the lack of significant differences between HCVrA and RA patients. Low circulating levels could be explained with the fact that IFN-gamma is not an isolate cytokine, but a piece of composite system regulated in a complex fashion, with many different factors contributing.
20576219 Development of TNF inhibitor therapies for the treatment of rheumatoid arthritis. 2010 May The recognition of tumor necrosis factor-alpha (TNF-alpha) as an important mediator of pathogenesis in rheumatoid arthritis (RA) led to the development of TNF inhibitors (TNFIs), which are a significant advance in the treatment of this debilitating disease. TNFIs revolutionized RA clinical practice, providing broader treatment options and establishing low disease activity and remission as achievable goals for many patients. Numerous clinical trials have shown that TNFIs are very effective, either as combination therapy or as monotherapy, in reducing the signs and symptoms of disease and slowing or inhibiting radiographic joint damage progression. Despite some adverse effects relating most frequently to infections and skin reactions, TNFIs are generally well tolerated in most patients and are widely recommended in clinical practice, in combination with good clinical judgment and individualized patient care.
19635908 Peptidoglycan enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, fo 2009 Aug 15 Peptidoglycan (PGN), the major component of the cell wall of Gram-positive bacteria, activates the innate immune system of the host and induces the release of cytokines and chemokines. We investigated the signaling pathway involved in IL-6 production stimulated by PGN in rheumatoid arthritis synovial fibroblasts. PGN caused concentration- and time-dependent increases in IL-6 production. PGN-mediated IL-6 production was attenuated by TLR2 small interfering RNA and nucleotide-binding oligomerization domain 2 small interfering RNA. Pretreatment with PI3K inhibitor (Ly294002 and wortmannin), Akt inhibitor, and AP-1 inhibitor (tanshinone IIA) also inhibited the potentiating action of PGN. PGN increased the focal adhesion kinase (FAK), PI3K, and Akt phosphorylation. Stimulation of rheumatoid arthritis synovial fibroblast cells with PGN increased the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to the AP-1 element on the IL-6 promoter. PGN mediated an increase in the accumulation of phosphorylated c-Jun in the nucleus, AP-1-luciferase activity, and c-Jun binding to AP-1 element was inhibited by Ly294002, Akt inhibitor, and FAK mutant. Our results suggest that PGN increased IL-6 production in human synovial fibroblasts via the TLR2 receptor/FAK/PI3K/Akt and AP-1 signaling pathway.
21153677 Non-invasive screening of progressive joint defects in the Type II collagen-induced arthri 2011 May OBJECTIVE: This study presents a method for non-invasive screening of progressive arthritic reactions in a representative rheumatoid arthritis (RA) animal model of Type II collagen-induced arthritis (CIA). MATERIALS: Seventeen male DBA/1J mice (9 weeks old) were used for the control group (seven) and the CIA group (ten). TREATMENT: The CIA model was induced by the injection of a Type II collagen and incomplete Freund's adjuvant emulsion. METHODS: Arthritic reactions including joint space narrowing (JSN), bone erosion, inflammation, and physiological defects were observed using five non-invasive methods. The degrees of JSN and bone erosion were quantified using macro-radiographs of specific joints and bones, while the severity of inflammation was evaluated by changes in paw volume and visual scoring of edema and erythema. RESULTS: Significant differences were observed in JSN (≤48.29%, p < 0.0001), bone erosion (78.30%, p < 0.0001), grip strength (p < 0.05), and inflammation (91.67% in edema and 194.12% increase in paw volume, p < 0.001) between the CIA group and the controls. The relationships between factors exhibited significant positive correlations (R ≥ 0.9229, p < 0.05) between radiographic parameters, with symmetries of ≥0.9062 (p < 0.05) for JSN and ≥ 0.8575 (p < 0.001) for bone erosion, 0.8770 (p < 0.0001) for inflammatory parameters, and ≥0.9527 (p < 0.0001) for radiographic and non-radiographic parameters. CONCLUSIONS: Our non-invasive radiographic and non-radiographic methods of documentation were both acceptable for screening joint defects during RA progression. In addition, the results of this study may be useful for monitoring the progression of joint pathology in RA diseases.
19291350 Use of tumor necrosis factor-alpha (TNF-alpha) antagonists infliximab, etanercept, and ada 2009 Jul An understanding of the cytokine cascade in a rheumatoid joint has led to the development of new therapeutic options, including drugs targeting tumor necrosis factor-alpha (TNF-alpha). The safety profile of these agents in patients with hepatitis-induced liver disease, however, remains a concern because of risks associated with immune suppression. To examine the effect of three different TNF-alpha antagonists, infliximab, etanercept, and adalimumab, on serum transaminases and hepatitis viral load in patients with rheumatoid arthritis (RA) and concurrent hepatitis B (HBV) or hepatitis C (HCV). Medical records of 11 patients with diagnosis of RA and documented seropositivity for hepatitis B or hepatitis C were retrospectively reviewed for worsening of hepatic inflammation and viral proliferation as measured by a rise in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) and viral load while using these agents. Three patients had RA with concurrent chronic HBV and eight patients had RA with concurrent chronic HCV. Seven patients remained on a single anti-TNF-alpha agent and four patients switched to a second anti-TNF-alpha agent due to treatment failure. Two patients showed a transient elevation in AST and/or ALT from normal, but in all 11 patients, AST and ALT levels were within one time the upper range of normal at the conclusion of the study. No significant increase in viral load was seen except one patient who showed a fourfold increase from baseline. Our case series supports results obtained from previous studies examining the safety of anti-TNF-alpha agents in patients with underlying hepatic disease. Use of these agents in patients with HBV or HCV may be associated with a transient transaminitis but appears to be safe overall. In both groups, frequent monitoring of serum transaminase levels and viral load is essential.
20696679 Improved treatment strategies reduce the increased mortality risk in early RA patients. 2010 Nov OBJECTIVE: A higher mortality rate in patients with RA than in the general population has been reported in most series. Treatment strategies for RA have improved dramatically over the last decades, resulting in less inflammation and joint damage. We investigated whether this change in treatment corresponds to reversal of excess mortality by studying a large inception cohort of early RA patients exposed to different treatment strategies. METHODS: Six hundred and eighty-four RA patients included in the Leiden Early Arthritis Clinic between 1993 and 2008 were studied. Treatment was different for three inclusion periods. From 1993 to 1995 patients were treated with NSAIDs and only late in their disease with DMARDs. From 1996 to 1998 patients were promptly treated with HCQ or SSZ. From 1999 to 2008 patients were immediately treated with MTX monotherapy or in combination with other disease-modifying drugs. Life/death status was tracked nationally using the civic registries. Mortality rates were compared with the general Dutch population. RESULTS: In Periods 1 and 2, increased standardized mortality rates were found, 1.35 (95% CI 0.94, 1.93) and 1.23 (95% CI 0.91, 1.67), respectively, while a decreased standardized mortality rate was found for patients included in 1999-2006 [0.49 (95% CI 0.31, 0.77)]. Age of onset [hazard ratio (HR) 1.10 (95% CI 1.07, 1.13)], erosive disease [HR 2.03 (95% CI 1.22, 3.37)], high CRP level [HR 1.09 (95% CI 1.01, 1.18)], smoking [HR 2.39 (95% CI 1.31, 4.38)] and higher baseline HAQ score [HR 1.53 (95% CI 1.06, 2.20)] associated with mortality. CONCLUSION: Current treatment strategies for early RA, such as that given in inclusion Period 3, might contribute to the reversal of excess mortality in RA.
19865842 Development of a framework for reporting health service models for managing rheumatoid art 2010 Feb The purpose of this study was to develop a framework for reporting health service models for managing rheumatoid arthritis (RA). We conducted a search of the health sciences literature for primary studies that described interventions which aimed to improve the implementation of health services in adults with RA. Thereafter, a nominal group consensus process was used to synthesize the evidence for the development of the reporting framework. Of the 2,033 citations screened, 68 primary studies were included which described 93 health service models for RA. The origin and meaning of the labels given to these health service delivery models varied widely and, in general, the reporting of their components lacked detail or was absent. The six dimensions underlying the framework for reporting RA health service delivery models are: (1) Why was it founded? (2) Who was involved? (3) What were the roles of those participating? (4) When were the services provided? (5) Where were the services provided/received? (6) How were the services/interventions accessed and implemented, how long was the intervention, how did individuals involved communicate, and how was the model supported/sustained? The proposed framework has the potential to facilitate knowledge exchange among clinicians, researchers, and decision makers in the area of health service delivery. Future work includes the validation of the framework with national and international stakeholders such as clinicians, health care administrators, and health services researchers.
19470526 PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian populat 2010 Apr BACKGROUND: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population. METHODS: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study. RESULTS: The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). CONCLUSION: In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.
21041278 Effect of atorvastatin on inflammation and modification of vascular risk factors in rheuma 2011 Feb OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.
19671813 Reappraisal of OMERACT 8 draft validation criteria for a soluble biomarker reflecting stru 2009 Aug OBJECTIVES: A draft set of criteria for the validation of soluble biomarkers reflecting damage endpoints was proposed at OMERACT 8. At OMERACT 9 we aimed to scrutinize the necessity for each of these criteria according to the objectives of the working group. METHODS: The OMERACT 8 draft criteria and the principle objectives of the validation process were clarified at a meeting of the working group in London, December 2007. A new framework was proposed after the following steps were conducted: (A) A systematic review of the literature focusing on the draft criteria and a preselected group of biomarkers (MMP3, CTX-II, RANKL, OPG, CTX-I) followed by a Delphi consensus exercise addressing the importance of individual criteria and identification of omissions in the draft set. (B) Formal debate as well as group discussion centered on the key arguments for inclusion/exclusion of specific criteria. (C) Onsite interactive electronic voting on the importance of specific criteria. The framework was presented and discussed at OMERACT 9 in both breakout and plenary sessions followed by a vote on its acceptance. RESULTS: The objectives of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis biomarkers in relation to their predictive validity for damage endpoints was clarified and supported by OMERACT 9 participants. The OMERACT 8 draft validation criteria were reformulated into an essential category focused on criteria addressing the OMERACT Filter elements of discrimination (incorporating truth) and feasibility, and a desirable but nonessential category of other criteria addressing truth. This revised draft set was endorsed by participants at OMERACT 9. CONCLUSION: A revised set of validation criteria has been drafted by consensus at OMERACT 9 that focuses on the performance characteristics of biomarker assays, the importance of addressing potential confounders, and the essential requirement for clinical validation studies.
19296301 Mechanical stretch regulates the expression of matrix metalloproteinase in rheumatoid arth 2009 Mechanical stretch plays a crucial role in articular joints. In rheumatoid arthritis (RA), it is well known that fibroblast-like synoviocytes (FLS) produce matrix metalloproteinases (MMPs), resulting in local invasion into and degradation of bone and cartilage. We sought to examine whether mechanical stretch regulates the expression and underlying signal pathways of MMP secretion (MMP-1, -3, -13) in RA-FLS. FLS were grown on elastic silicone membrane in an equibiaxial strain apparatus and were exposed to 6% mechanical stretch (equivalent to gentle stretch exercise) for 15 min and 75 min, respectively. Semiquantitative PCR and real-time PCR were used to measure and analyze gene expression. Protein levels were determined by Western blotting. The results showed that 15 min of mechanical stretch inhibited MMP-1 and MMP-13 mRNA and protein level. However, the degree of inhibition by 75 min of stretch in expression of MMP-1 and MMP-13 was lower compared with 15 min stretch groups. The mRNA expression of ERK-1, ets-1 and citied-2 were increased by 6% mechanical stretch under both time points, however c-jun and c-fos mRNA level were affected differently after 15 min and 75 min mechanical stretch compared to control group. There were no significant changes on MMP-3 and ets-2 mRNA level under both 6% mechanical stretch time points. In the presence of pro-inflammatory cytokines (IL-1beta and TNF-alpha), the stretch also reduced the mRNA expression of MMP-1 and MMP-13. In short, our results showed that gentle mechanical strain affects MMP-1 and MMP-13 expression, potentially through the ERK-1-ets-1-cited-2-c-jun signaling pathway.
19202302 Effects of an oral administration of glucosamine-chondroitin-quercetin glucoside on the sy 2009 Feb The effects of an orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement on the synovial fluid properties of patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were investigated from the clinical nutrition view point. In this study, forty-six OA and twenty-two RA patients were administered with the GCQG supplement orally for 3 months. Several parameters of the knee joints were monitored before and after supplementation. The OA patients showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties with respect to the protein concentration, molecular size of hyaluronic acid, and chondroitin 6-sulphate concentration were also observed. However, no such effects were observed in the RA patients. These results suggest that the GCQG supplement exerted a special effect on improving the synovial fluid properties in OA patients.
19109035 Inflammatory demyelinating events following treatment with anti-tumor necrosis factor. 2009 Feb BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine involved in certain inflammatory diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease. The anti-TNF-alpha treatments used for RA may be associated with inflammatory demyelinating events affecting the central nervous system and may possibly aggravate known MS. OBJECTIVE: We report here three new cases of inflammatory demyelinating events of the central nervous system following treatment with anti-TNF-alpha. RESULTS: The neurological symptoms appeared on average 5 months after initiation of the treatment. For all patients, the inflammatory process was confirmed by brain magnetic resonance imaging. The symptoms totally or partially regressed as soon as anti-TNF-alpha treatment was stopped except for one patient who developed clinically defined MS. CONCLUSIONS: Inflammatory demyelination of the central nervous system may be associated with the use of anti-TNF-alpha. Patients with rheumatoid arthritis treated with these treatments should benefit from a follow-up which includes brain MRI.
20457731 Anti-cyclic citrullinated peptide antibodies and rheumatoid factor in rheumatoid arthritis 2010 Aug OBJECTIVES: To evaluate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies and RF in RA patients and their relatives from Southern Brazil. METHODS: Anti-CCP2 and IgM-RF were evaluated in 156 RA patients and 200 relatives. Sera from 100 healthy unrelated individuals were used as control. The anti-CCP2 was detected by ELISA and the IgM-RF using the latex agglutination test. RESULTS: We identified 117 anti-CCP2 (75%)-positive and 106 RF (67.9%)-positive patients. Anti-CCP2 was increased in relatives (5.5%; 11/200) when compared with unrelated individuals (1%; P = 0.050). Titre of anti-CCP2 in RA patients did not differ from relatives [140.4 (75.7) vs 115.6 (84.2) U, respectively; P = 0.30]. Positive relatives were younger than patients for anti-CCP2 (P = 0.0081), RF (P < 0.001) and both concomitantly (P = 0.012), and although there was no difference for anti-CCP2 positivity according to gender, increased RF positivity and concomitant anti-CCP2/RF were observed in the female relatives (P = 0.067 and 0.082, respectively). No difference regarding the relative degree of tobacco use in relatives was detected. Among the 11 anti-CCP2-positive relatives, 2 females had RA diagnosis established and 6 individuals presented with joint symptoms suggestive of RA. CONCLUSION: The results demonstrate a significant positivity of anti-CCP2 in relatives of RA patients from Brazil and reinforce the importance of serological tools to identify undiagnosed RA.
20439295 Continued inhibition of structural damage over 2 years in patients with rheumatoid arthrit 2010 Jun BACKGROUND: Rituximab inhibited structural damage at 1 year in patients with rheumatoid arthritis (RA) who had had a previous inadequate response to tumour necrosis factor (TNF) inhibitors. OBJECTIVE: To assess structural damage progression through 2 years. METHODS: Intention-to-treat patients with one post-baseline radiograph (rituximab n=281; placebo n=187) received background methotrexate (MTX) and were randomised to rituximab (2 x 1000 mg infusions, 2 weeks apart) or placebo; patients were eligible for rituximab re-treatment every 6 months. By week 104, 82% of the placebo population had received > or = 1 dose of rituximab. Radiographic end points included the change in total Sharp score (TSS), erosion and joint space narrowing scores at week 104. RESULTS: At week 104, significantly lower changes in TSS (1.14 vs 2.81; p<0.0001), erosion score (0.72 vs 1.80; p<0.0001) and joint space narrowing scores (0.42 vs 1.00; p<0.0009) were observed with rituximab plus MTX vs placebo plus MTX. Within the rituximab group, 87% who had no progression of joint damage at 1 year remained non-progressive at 2 years. CONCLUSIONS: Rituximab plus MTX demonstrated significant and sustained effects on joint damage progression in patients with RA and a previously inadequate response to TNF inhibitors.
20131277 Left ventricular structure and function in patients with rheumatoid arthritis, as assessed 2010 Apr OBJECTIVE: Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. METHODS: With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. RESULTS: Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. CONCLUSION: These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume.
20954336 [Rheumatoid arthritis]. 2010 Oct Etiology of rheumatoid arthritis(RA) has not been clarified, however many candidate molecules for the target of RA treatment have been identified. Among those, regulation of TNF or IL-6 using antibodies or receptor molecules has brought a paradigm shift in the therapeutic strategy of RA and has become a standard therapy in daily practice. Many targeted therapy are now in the development for the treatment of RA, however, those target molecules are deeply involved in the immune function, and inhibition of these molecules may increase the susceptibility for infections. Also, using these expensive drugs for this chronic disease raises a pharmacoeconomical issue. There are many issues remaining to be solved.
20193007 Bone remodeling in rheumatic disease: a question of balance. 2010 Jan The past decade has observed an explosion of new information regarding the impact of inflammation on bone. In rheumatic diseases, several factors that act as both immune modulators and regulators of bone homeostasis have been shown to mediate an imbalance in bone resorption and bone formation resulting in joint degeneration. In rheumatoid arthritis (RA), focal bone loss is due to excess bone resorption by osteoclasts. Resorption is mediated in part by increased local expression of the cytokine receptor activator of nuclear factor-kappaB ligand (RANKL) compared with expression of its decoy receptor osteoprotegerin (OPG). Bone formation by osteoblasts is also impaired at erosion sites in RA, and inhibitors of the canonical Wingless (Wnt) signaling pathway, including DKK1, have been implicated in the suppression of normal osteoblast function at these sites. Inhibition of DKK1 in an animal model of RA attenuated bone erosion by increasing OPG expression as well as promoting bone formation. In contrast to RA, inflammation in the spondyloarthropathies often results in excess periosteal bone formation, highlighting that the net impact of inflammation on bone is specific to the site at which inflammation occurs, and the cell types, cytokines, and factors present within the local bone microenvironment. This fertile area of research bears watching for the identification of novel targets for the prevention of abnormal bone remodeling in inflammatory diseases.
19642861 Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal 2009 BACKGROUND: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. METHODS: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. RESULTS: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. CONCLUSIONS: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition.