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ID PMID Title PublicationDate abstract
19627580 Markers of B-lymphocyte activation are elevated in patients with early rheumatoid arthriti 2009 INTRODUCTION: Little is known about systemic B-cell activation in early rheumatoid arthritis (RA). We therefore evaluated the serum levels of markers of B-cell activation in patients included in the ESPOIR early arthritis cohort. METHODS: In the ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks but less than 6 months), 710 patients were assessed at 1 year and either met the 1987 American College of Rheumatology criteria for RA (n = 578) or had undifferentiated arthritis (n = 132). Baseline serum samples of patients naïve to corticosteroid and disease-modifying antirheumatic drug treatment were assessed for beta2-microglobulin, IgG, IgA, IgM, immunoglobulin free light chains of immunoglobulins, and B-cell activating factor of the tumor necrosis factor family (BAFF). The BAFF gene 871T>C polymorphism was genotyped in all patients. RESULTS: All markers of B-cell activation except BAFF and IgM were significantly higher in patients with early RA than those with undifferentiated arthritis. Anti-cyclic citrullinated peptide (anti-CCP) and beta2-microglobulin were associated with a diagnosis of early RA in the multivariate analysis. Markers of B-cell activation, except BAFF, were associated with disease activity, rheumatoid factor and anti-CCP secretion. The BAFF gene polymorphism was not associated with early RA. CONCLUSIONS: Markers of B-cell activation are elevated in patients with early RA, compared with undifferentiated arthritis, independently of any systemic increase in BAFF secretion, and correlate with disease activity. This study sheds new light on the early pathogenic role of B-lymphocytes in RA and suggests that targeting them might be a useful therapeutic strategy in early RA.
20132068 Cystatin C is a sensitive marker for detecting a reduced glomerular filtration rate when a 2010 OBJECTIVE: Chronic kidney disease is a predictor of end-stage renal disease, and evaluating the glomerular filtration rate (GFR) is necessary to make a definite diagnosis. We assessed the utility of serum cystatin C (cysC) for identifying a reduced GFR in patients who have rheumatoid arthritis (RA) with secondary amyloidosis. METHODS: Fifty patients with RA and secondary amyloidosis (mean age 60.9+/-11.2 years; 45 women) were evaluated. The revised 24-h creatinine clearance (r24-hC(Cr)), which was determined by multiplying the original value by 0.719, was used as a reference for the GFR. The screening potential of the serum cysC and some estimates of the GFR calculated from the serum cysC (cysC-eGFR: eGFR(Hoek) and eGFR(Rule)) for detecting a reduced GFR (r24-hC(Cr)<60 mL/min/1.73 m(2)) were analysed. RESULTS: Both cysC-eGFRs were strongly correlated with the r24-hC(Cr) (eGFR(Hoek), r=0.846, p<0.001; eGFR(Rule), r=0.820, p<0.001). The difference between the average eGFR(Rule) (37.1+/-31.2 mL/min/1.73m(2)) and average r24-hC(Cr) (35.3+/-30.9 mL/min/1.73 m(2)) was small, whereas eGFR(Hoek) and sCr-eGFR were higher than eGFR(Rule) and r24-hC(Cr). In receiver operating characteristic (ROC) curve analyses of a reduced GFR, serum cysC gave a greater area under the curve (AUC=0.958) than the sCr-eGFR (0.939-0.942). The specificity and positive predictive value (PPV) reached 100% when serum cysC >1.365 mg/L was used. CONCLUSIONS: Serum cysC can identify a reduced GFR more accurately than sCr-eGFRs. Serum cysC >1.09 mg/L (i.e. eGFR(Rule)<60 mL/min/1.73 m(2)) could be a marker of a reduced GFR, and serum cysC >1.365 mg/L would strongly suggest a reduced GFR in patients who have RA with secondary amyloidosis.
20931156 Pain assessment in fibromyalgia and rheumatoid arthritis: influence of physical activity a 2010 OBJECTIVE: Pain visual analog scales (VAS) have been validated for clinical use in fibromyalgia (FM) and rheumatoid arthritis (RA) patients. There are potential limitations, however, not only considering their use as a continuous measurement, but also with regard to the influence of personal illness perceptions, habitual physical activity and other life-style features. The aim of the study was to ascertain whether different illness perception, physical activity and clinical and laboratory characteristics can predict the severity of perceived pain assessed by VAS. MATERIALS AND METHODS: This is an observational comparative study of forty consecutive out-patients, 20 of them with fibromyalgia and 20 with rheumatoid arthritis, treated by medical and physical therapy. Patients were assessed also by Pain VAS, Health Assessment Questionnaire (HAQ) disability index, Ritchie index, Baecke questionnaire for physical activity, Illness Perception Questionnaire (IPQr) and SF36. RESULTS: Pain VAS is explained differently by some of the studied variables: in the total group HAQ and Ritchie index explain 29.8% of the variance; in the RA patients number of joints with pain and Ritchie index explain 52.7% of the variance; in FM patients total SF36 score and IPQr personal control dimension explains 44.7% of the variance. No definite role of anxiety and/or depression was found as predictor of perceived pain and disability. CONCLUSION: Pain perception and complaint are explained by belief in FM patients: This seems to suggest the need for a more articulated cognitive approach; addressing both diagnostic and therapeutic interventions to anxiety/depression issues is not supported by our results.
20067160 Endothelial dysfunction in inflammatory rheumatic diseases. 2009 The importance of cardiovascular disease in inflammatory rheumatic diseases was recognized as one of the determinants of increased mortality in these patients. An increased cardiovascular disease was reported in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but also in other rheumatic diseases. Several hypotheses were elaborated, but the chronic inflammatory status seems to be a primordial factor. Therefore, the diagnostic and treatment of cardiovascular disease, even in subclinical status, should be one of most important goals in the global management of these patients. The endothelial dysfunction is now regarded as an important and early step in the processes that promote atherosclerosis. In patients with inflammatory rheumatic diseases, the presence of the endothelial dysfunction was reported and linked with several clinical or biological features of each disease. Moreover, the potential benefits on the endothelial dysfunction of several therapies were assessed especially in patients with RA or SLE. The aim of this article is to review the impact of the endothelial dysfunction and the methods to improve it in patients with these conditions.
18230627 The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in r 2009 Jan BACKGROUND: Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established. OBJECTIVE: To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA. METHODS: All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders. RESULTS: The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10-37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged. CONCLUSION: Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.
20009966 Prevalence of antinuclear antibodies in 3 groups of healthy individuals: blood donors, hos 2009 Oct Antinuclear antibodies (ANA) are frequently found in healthy populations. To define the prevalence, pattern, and titer of ANA in different groups of the healthy Mexican population, we studied 304 individuals, classified into 3 groups: 104 blood donors, 100 hospital personnel working at The State General Hospital, which included doctors, laboratory technicians, and nurses; and 100 relatives of patient diagnosed either with systemic lupus erythematosus or rheumatoid arthritis, all of them apparently healthy at the time of study. We determined ANA using immunofluorescence microscopy performed on HEp-2 cells. Fluorescence was detected in 165 serum samples (54.3%). The most frequent pattern was the speckled (50.3%). The most frequent dilution was 1:40 (35.4%), followed by 1:80 (13.4%), 1:160 (3.2%), and 1:320 (1.3%).Regarding the results by study group, we found a trend toward higher ANA levels in group 2 (hospital personnel), compared with group 1 (blood donors) and group 3 (relatives of patients), a trend also reflected by the increasing frequency of serum titers of 1:80 and higher (P = 0.074). According to occupation, medical doctors showed a higher incidence of speckled pattern when compared with other occupations (P = 0.022). Medical doctors (n = 75) showed also higher titers of this particular pattern (P = 0.03). In group 3, relatives of patients with systemic lupus erythematosus showed the speckled pattern more frequently than relatives of patients with rheumatoid arthritis, in low titers (P = 0.017). We suggest that ANA tests showing speckled pattern should be at a 1:160 titer or higher to be considered positive; other patterns such as homogeneous, peripheral, or centromeric might be considered positive even at low titers (
20735353 Prostanoid receptors as possible targets for anti-allergic drugs: recent advances in prost 2010 Dec Prostanoids, consisting of prostaglandins and thromboxane, are cyclooxygenase metabolites of arachidonic acid released in various pathophysiological conditions which exert a range of actions mediated through their respective receptors expressed on target cells. Although it has been difficult to analyze the physiological role of prostanoids, recent developments in both the disruption of the respective gene and receptor selective compounds have enabled us to investigate the physiological roles for each receptor. It has been demonstrated that each prostanoid receptor has multiple functions, and that their expression is regulated in a context-dependent manner that sometimes results in opposite, excitatory and inhibitory, outcomes. The balance of prostanoid production and receptor expression has been revealed to be important for homeostasis of the human body. Here, we review new findings on the roles of prostanoids in allergic and immune diseases, focusing on contact dermatitis, atopic dermatitis, asthma, rheumatoid arthritis, and encephalomyelitis, and also discuss the clinical potentials of receptor-selective drugs.
20563870 The PADI4 gene does not contribute to genetic susceptibility to rheumatoid arthritis in Ch 2011 Dec The Peptidyl arginine deiminase, type IV (PADI4) gene has been suggested to have an association with rheumatoid arthritis (RA) in several populations. But its role in Chinese RA is not clarified. We investigated five single-nucleotide polymorphisms (SNPs) of PADI4 as PADI4-89 (rs11203366), PADI4-90 (rs11203367), PADI4-92 (rs874881) PADI4-94 (rs2240340), and PADI4-104 (rs1748033) in Chinese Han population. A total of 378 unrelated RA patients and 204 healthy controls were genotyped for the five SNPs. Individual allele, genotype and haplotype frequencies were compared between patients and controls. No significant differences in the frequency of PADI4 alleles, genotypes and haplotypes were observed between the patients and controls except PADI4-92. These data indicated that PADI4 polymorphisms were unlikely to play an important role in the susceptibility to RA in Chinese Han population.
19252371 [Dopamine as an immune-modulator between dendritic cells and T cells and the role of dopam 2009 Feb The nerve systems affect immune functions by releasing neurotransmitters through lymphocyte cell-surface receptors. A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. There is wide evidence for a decreased risk of rheumatoid arthritis (RA) in patients with schizophrenia which is associated with the excessive stimulation of D2-like receptors by dopamine. However, the reason for the negative association between RA and schizophrenia is unknown. We previously demonstrated that dendritic cells (DCs) could synthesize and store dopamine, DC released dopamine to naive CD4 T cells upon DC-T cell interaction and affected helper T-cell differentiation. Because DCs have been proposed to play a pivotal role in the initiation and perpetuation of RA by presentation of arthritogenic antigens to T cells, we here assessed effects and functions of dopamine on immune cells during the pathogenesis of RA. In this paper, we overview the series of our research findings, and present the possibility of drug discovery which target at dopamine receptors.
20358496 [Interdisciplinary emergencies in rheumatic diseases]. 2010 Apr Rheumatic disease can affect and severely damage vital organs and thus cause acute emergencies and life-threatening complications. As systemic diseases they can cause any presenting complaint commonly encountered in emergency medicine. Because of their relative rarity in general practice, a high level of vigilance is required in order to recognize an emergency caused by an underlying rheumatic disease in individual cases. The most important rheumatological emergencies comprise septic arthritis, gout, atlantoaxial subluxation, renal crisis and digital ulcers in systemic sclerosis, amaurosis fugax in giant cell arteritis, the catastrophic anti-phospholipid antibody syndrome and the pulmonary-renal syndrome. This article provides an overview over these rheumatological emergencies in order to aid recognition of these entities in individual cases and to thus facilitate immediate and adequate treatment, which is of vital importance for affected patients.
21047485 Certolizumab pegol (CIMZIA®) for the treatment of rheumatoid arthritis. 2010 Oct This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of certolizumab pegol (CZP) for adults with active rheumatoid arthritis (RA) that have not responded adequately to treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX), in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcome measures included American College of Rheumatology (ACR) 20, 50 and 70 response rates and quality of life measures after 3 months and 6 months of treatment. The ERG examined the submission's search strategies and considered they appeared comprehensive and that it was unlikely that relevant studies would have been missed. Only English language studies were considered in the submission and non-English language studies relevant to the decision problem may possibly have been ignored. The ERG analysed the first submitted economic model so as to itemise in detail clarification points that were brought to the attention of the manufacturer. In response the manufacturer submitted a modified cost-effectiveness analysis. The ERG undertook further analysis of this second model and other additional submitted evidence. The clinical evidence was derived from two multicentre blinded randomised controlled trials (RCTs) comparing CZP + MTX to placebo + MTX (the RAPID 1 and RAPID 2 trials). RAPID 1 lasted 52 weeks with 982 patients and RAPID 2 24 weeks with 619 patients. Evidence for clinical effectiveness of CZP in mono-therapy came from the 24-week FAST4WARD trial with 220 patients that compared CZP (400 mg every 4 weeks) versus placebo. The three key RCTs demonstrated statistically significant superiority of CZP + MTX versus placebo + MTX and of CZP versus placebo with respect to a variety of outcomes including ACR 20, ACR 50 and ACR 70 measures and quality of life measures at 3 and 6 months. On the basis of results from the indirect comparison meta-analyses, the manufacturer suggested that CZP may be at least as effective as other 'biological' DMARD (bDMARD) comparators and, in a few ACR measures at 3 and 6 months, more effective. CZP is an effective therapy for adult RA patients whose disease has failed to respond adequately to cDMARDs including MTX or who are intolerant of MTX. The cost-effectiveness of CZP relative to other bDMARDs is unclear because the economic modelling undertaken may have ignored relevant effectiveness data and potential differences between trial populations, and so may have included effectiveness results that were biased in favour of CZP; underestimated uncertainty in the relative effectiveness of compared DMARDs; and ignored the potential influence of differences between bDMARDs with regard to adverse events and their related costs and health impacts. The NICE guidance issued in October 2009 states that: the Committee is minded not to recommend certolizumab pegol as a treatment option for people with RA; and the Committee recommends that NICE asks the manufacturer of CZP for more information on the clinical effectiveness and cost-effectiveness of CZP for the treatment of people with RA. On receipt of this information and details of a patient access scheme NICE issued final guidance recommending CZP, under certain criteria, as a treatment option for people with RA.
20691795 Treatment with TNF-α inhibitor infliximab might reduce hand osteoarthritis in patients wi 2010 Oct OBJECTIVES: To investigate the association between systemic and local inflammation and incident and progressive radiographic secondary osteoarthritis (OA) in interphalangeal joints (IPJs) over 3 years in rheumatoid arthritis (RA) patients and the effect of tumor necrosis factor alpha (TNF-α) inhibitor infliximab on secondary OA in IPJs. METHODS: In the present observational longitudinal study baseline and 3-year hand X-rays of 416 recent-onset RA patients were scored for osteophytes and erosions in IPJs, blinded for time, using Osteoarthritis Research Society International atlas and Sharp-van der Heijde score. The associations between inflammatory factors and incident and progressive secondary OA in distal IPJs (DIPJs) and proximal IPJs (PIPJs) and the effect of infliximab compared to disease-modifying anti-rheumatic drug treatment on secondary OA were analyzed by multivariable regression and generalised estimating equations analyses. RESULTS: Sixty-seven percent of the patients were female with, at baseline, a mean age of 54 years and OA present in DIPJs and PIPJs in 37% and 13%. Three years later, new secondary OA in DIPJs and PIPJs was seen in 11% and 10%, and progressive secondary OA in 36% and 35%. High erythrocyte sedimentation rate over 3 years and progressive erosive damage were risk factors for incident secondary OA in DIPJs, but not in PIPJs. At joint level, progression of erosions was associated with both incident and progressive secondary OA, only in DIPJs. Infliximab treatment was associated with lower incident secondary OA in PIPJs [relative risk 0.5 (95% confidence interval 0.2, 1.0)], independent of decrease in inflammation. CONCLUSION: Incident and progressive secondary OA in DIPJs over 3 years was associated with high inflammatory activity in RA. Infliximab treatment reduced incident secondary OA in PIPJs independent of decrease in inflammation, suggesting that anti-TNF-α therapy might be effective against secondary hand OA via other pathways than suppression of inflammation. Further studies in populations of primary hand OA are necessary to determine the role of anti-TNF-α in treatment of primary hand OA.
20012964 The diagnostic utilities of anti-agalactosyl IgG antibodies, anti-cyclic citrullinated pep 2011 Mar The purpose of this study was to investigate the diagnostic utilities of anti-agalactosyl IgG antibody (CARF), anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor (RF) in rheumatoid arthritis (RA), non-RA rheumatic diseases, and chronic viral hepatitis. The authors determined serum levels of CARF and anti-CCP2 by ELISA and IgM-RF by a immunonephelometric method in 834 controls and in 397 patients with the following conditions: RA (100), non-RA rheumatic diseases [systemic lupus erythematosus (SLE) 30, primary Sjogren's syndrome 18, systemic sclerosis 30, inflammatory myositis 19], chronic viral hepatitis B and C (HBV 100, HCV 100). The sensitivities of CARF (83%) and anti-CCP (85%) were significantly higher than that of RF (75%, p = 0.01, respectively) in RA, and the specificity of anti-CCP (98%) was significantly higher than those of CARF (92%) and RF (90%, p < 0.001, respectively). A comparison of receiver operating characteristic (ROC) curves revealed that the diagnostic accuracies of CARF and anti-CCP were superior to that of RF (CARF vs. RF, p = 0.008, anti-CCP vs. RF, p = 0.017) in RA. CARF positivity was significantly higher than those of anti-CCP (p = 0.007) and RF (p = 0.008) in systemic sclerosis, and the positivity of CARF was significantly higher than that of anti-CCP in Sjogren's syndrome (p = 0.016). Furthermore, CARF had significantly higher positivity than anti-CCP or RF in chronic viral hepatitis B and C. Finally, the titers of these three markers in RA were significantly higher than in non-RA rheumatic diseases and in chronic viral hepatitis B and C. Our results suggest that anti-CCP is the most useful serologic marker for the differentiation of RA and non-RA rheumatic diseases, and chronic viral hepatitis B and C.
19373092 An update on methotrexate. 2009 May PURPOSE OF REVIEW: Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about three decades now. MTX is one of the most effective and commonly used medicines to treat various forms of arthritis and other rheumatic conditions. MTX was shown to improve signs and symptoms of RA, disease activity and function, to a similar degree as the tumor necrosis factor blockers, and it inhibits radiographic progression to a smaller degree than the antitumor necrosis factor agents. MTX is considered as the anchor drug among the disease-modifying antirheumatic agents, and it is internationally accepted as the first choice in the management of RA. This review was performed on the basis of a PubMed literature search looking at all publications on MTX and arthritis in 2008. RECENT FINDINGS: MTX seems to even prolong the life span of patients who tolerate the drug and have clinical benefit from this therapy; this may partly be explained by beneficial effects on cardiovascular mortality. The reason for this may well be the suppression of inflammation, but direct atheroprotective effects of MTX may also play a role. MTX is used as monotherapy and in combination with other disease-modifying antirheumatic agents or biologic agents such as the antitumor necrosis factor agents. The 'early' use of MTX within 5 years after disease onset is clearly associated with improved outcomes. The management of RA should include an early strong suppression of inflammation and continuously a tight control strategy. The pharmacodynamics and kinetics of MTX are still incompletely understood. SUMMARY: In this review, we especially cover the following themes: new clinical studies on the use of MTX in RA, the use of MTX in other rheumatic conditions, prediction of response to MTX, optimal dosage, MTX use in the elderly, the mechanism of action, the pharmacokinetics and the pharmacogenetics of MTX, the prevention of side effects, and the overall long-term safety.
20536422 CC chemokine receptor small molecule antagonists in the treatment of rheumatoid arthritis 2010 CC chemokines and their receptors play a key role in mediating both physiological and pathological processes. Chemokine receptors have been widely recognized as attractive drug targets by the pharmaceutical industry. A number of small molecule chemokine receptor antagonists have been developed for different disease indications, including rheumatoid arthritis (RA). This article describes the pharmacological evidence to support the therapeutic potential of targeting chemokine receptors, and highlights some of the recent progress in the field of developing small molecule antagonists for CC chemokine receptors aiming for RA and other disease applications. Furthermore, with the unsatisfactory clinical success so far, potential solutions leading to better success rates are also discussed.
19263389 [Quality of life in multiple sclerosis and other chronic autoimmune and non-autoimmune dis 2009 Mar 1 INTRODUCTION: Diseases that involve the nervous system and the musculoskeletal system are particularly likely to produce different limitations and deficits, and to affect the individual conception of quality of life. AIM: To determine the impact on quality of life generated by chronic autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), ankylosing spondylitis (AS) and chronic musculotendinous diseases like osteoarthritis (OA) and fibromyalgia (FM), using the Short Form 36-item (SF-36) health questionnaire. PATIENTS AND METHODS: A descriptive cross-sectional study was conducted between January 2004 and June 2006 and included 509 individuals, of whom 56 had MS, 36 SS, 24 AS, 200 RA, 65 SLE, 54 OA and 74 FM. Guided interviews were conducted to evaluate each sphere of the SF-36 health questionnaire. The statistical analysis was performed using the general lineal model, with means differences according to each diagnosis. RESULTS: Compared to patients with RA, those with MS showed significant differences in the physical functioning and social functioning dimensions. The lowest score was recorded in those with FM, except in physical functioning, where MS had the lowest mean. No differences were found in the mean scores on general conception of the state of health in each condition analysed. CONCLUSIONS: Different neurological functions deteriorate progressively in MS, which has repercussions on the musculoskeletal system; this leads to a poorer quality of life, mainly in the physical and social functions. The disability generated is not only defined by deficit but also by the degrees of functional limitation within the context of personal health. Quality of life thus becomes a global biopsychosocial phenomenon.
20171744 Increased urinary free immunoglobulin light chain excretion in patients with multiple scle 2010 Mar 30 BACKGROUND: Plasma and B cells are implicated in multiple sclerosis (MS) and produce free light chains (FLC) that are excreted in urine. OBJECTIVE: To confirm that demyelinating diseases (DD) cause increased urinary FLCs. METHOD: Urinary FLC in 50 patients with DD were compared to 20 patients with posterior uveitis (PU), 19 with AIDS, 34 with rheumatoid arthritis (RA) and 19 normal controls (NC). RESULT: Subjects with DD, PU, RA and AIDS have higher urinary FLCs than NC (p<0.01). Urinary FLCs did not correlate with gadolinium-enhancing lesions on MRI. CONCLUSIONS: Urinary FLCs are raised in DD. Further studies are required to see if they correlate with disease activity.
20483756 Regulatory T cells protect from local and systemic bone destruction in arthritis. 2010 Jun 15 We previously demonstrated the suppressive effects of regulatory T cells (Treg cells) on osteoclast differentiation in vitro. In this article, we show that blood markers of bone resorption inversely correlate with the amount of circulating Treg cells in healthy controls and rheumatoid arthritis patients, further suggesting that Treg cells may control bone destruction in vivo. Indeed, bone marrow from Foxp3-transgenic (Foxp3tg) mice fully protected human TNF transgenic (hTNFtg) mice from TNF-alpha-induced bone destruction, whereas Foxp3-deficient bone marrow enhanced local and systemic bone loss. The same protective effect was also obtained by treating hTNFtg mice with the CD28 superagonist mAb (CD28 SA), which increased Treg cell numbers. In both models, bone protection by Treg cells was associated with reduced osteoclast numbers, resulting in less bone-resorbing activity. Reduced osteoclast numbers were not caused by an intrinsic defect in osteoclast differentiation because osteoclast precursors from hTNFtg/Foxp3tg chimeras responded normally to M-CSF and receptor activator of NF-kappaB ligand. Although a decrease in the clinical signs of arthritis was observed in Foxp3tg bone marrow-transferred and CD28 SA-treated hTNFtg mice, the bone-protective effect of Treg cells was independent of the suppression of inflammation, as demonstrated by the increased systemic bone density observed in wild-type mice treated with CD28 SA. This work demonstrated that increasing Treg cell numbers improved clinical signs of arthritis and suppressed local and systemic bone destruction. Thus, enhancing the activity of Treg cells would be beneficial for the treatment of inflammation-induced bone loss observed in rheumatoid arthritis.
20110505 Platelets amplify inflammation in arthritis via collagen-dependent microparticle productio 2010 Jan 29 In addition to their pivotal role in thrombosis and wound repair, platelets participate in inflammatory responses. We investigated the role of platelets in the autoimmune disease rheumatoid arthritis. We identified platelet microparticles--submicrometer vesicles elaborated by activated platelets--in joint fluid from patients with rheumatoid arthritis and other forms of inflammatory arthritis, but not in joint fluid from patients with osteoarthritis. Platelet microparticles were proinflammatory, eliciting cytokine responses from synovial fibroblasts via interleukin-1. Consistent with these findings, depletion of platelets attenuated murine inflammatory arthritis. Using both pharmacologic and genetic approaches, we identified the collagen receptor glycoprotein VI as a key trigger for platelet microparticle generation in arthritis pathophysiology. Thus, these findings demonstrate a previously unappreciated role for platelets and their activation-induced microparticles in inflammatory joint diseases.
21103793 New therapeutic approaches for the treatment of rheumatoid arthritis may rise from the cho 2010 Nov 16 Due to the complex etiology of rheumatoid arthritis (RA), it is difficult to be completely cured at the current stage although many approaches have been applied in clinics, especially the wide application of nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). New drug discovery and development via the recently discovered cholinergic anti-inflammatory and antinociceptive pathways should be promising. Based on the above, the nicotinic acetylcholine receptor agonists maintain the potential for the treatment of RA. Therefore, new therapeutic approaches may rise from these two newly discovered pathways. More preclinical experiments and clinical trials are required to confirm our viewpoint.