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ID PMID Title PublicationDate abstract
18802115 Stimulatory role of lysophosphatidic acid in cyclooxygenase-2 induction by synovial fluid 2008 Oct 1 While inflammatory cytokines are well-recognized critical factors for the induction of cyclooxygenase-2 (COX-2) in activated fibroblast-like synovial cells, the roles of biologically active components other than inflammatory cytokines in synovial fluid remain unknown. Herein, we assessed the role of lysophosphatidic acid (LPA), a pleiotropic lipid mediator, in COX-2 induction using synovial fluid of patients with rheumatoid arthritis (RA) in fibroblast-like RA synovial cells. Synovial fluid from RA patients stimulated COX-2 induction, which was associated with prostaglandin E(2) production, in RA synovial cells. The synovial fluid-induced actions were inhibited by G(i/o) protein inhibitor pertussis toxin and LPA receptor antagonist 3-(4-[4-([1-(2-chlorophenyl)ethoxy]carbonyl amino)-3-methyl-5-isoxazolyl] benzylsulfanyl) propanoic acid (Ki16425). In fact, LPA alone significantly induced COX-2 expression and enhanced IL-1alpha- or IL-1beta-induced enzyme expression in a manner sensitive to pertussis toxin and Ki16425. RA synovial cells abundantly expressed LPA(1) receptor compared with other LPA receptor subtypes. Moreover, synovial fluid contains a significant amount of LPA, an LPA-synthesizing enzyme autotaxin, and its substrate lysophosphatidylcholine. In conclusion, LPA existing in synovial fluid plays a critical role in COX-2 induction in collaboration with inflammatory cytokines in RA synovial cells. Ki16425-sensitive LPA receptors may be therapeutic targets for RA.
17280816 Hoarseness due to bamboo nodes in patients with autoimmune diseases: a review of literatur 2008 May This is a retrospective report on clinical features, laryngoscopic examinations, and follow-up markers of laryngeal manifestation described as bamboo nodes in three female patients with transverse cystic lesions of the vocal folds, treated with logopedic therapy. This study examines logopedic and phoniatric aspects in patients with submucosal "bamboo joint-like nodes" of both vocal folds, and reveals an improvement of different voice quality features after conservative traditional voice therapy. There still exists no standard treatment regimen in patients with rheumatoid disease of the larynx; a lack of consensus is most evident in the role of voice therapy. We would like to emphasize the favorable impact of logopedic therapy in benign laryngeal disorders with underlying autoimmune diseases.
16446173 Glucocorticoid receptor beta in acute and chronic inflammatory conditions: clinical implic 2006 Glucocorticoids (GC) are hormones with a wide variety of actions, including profound anti-inflammatory/immunosuppressive effects. Their actions are mediated by an intracellular receptor called the glucocorticoid receptor (GCR). The classical GCR that mediates the hormone response is called GCR alpha. Recently however, many GCR isotypes have been described. A defective GC action has been proposed as an etio-pathogenic mechanism for the development of inflammatory/autoimmune diseases. Inadequate GC actions may have multiple causes such as: defective hypothalamic-pituitary-adrenal axis function, GC export from cells, hormone metabolization into inactive compounds and modifications of the GC receptor, among others. In 1995, a dominant negative effect of a GC receptor isotype termed beta was described; starting a still unsolved controversy about the role of GCR beta as an inducer of GC resistance in certain pathological conditions. The present article will review the data about a possible role for GCR beta in the development of GC resistance in inflammatory diseases. This review will especially focus on the role of the GCR beta in rheumatoid arthritis and in septic shock as examples of a chronic inflammatory disease and an acute systemic inflammatory condition. Original data supporting possible hyperexpression of GCR beta in both conditions will be shown.
16263778 Patients with stable long-standing rheumatoid arthritis continue to deteriorate despite in 2006 May OBJECTIVE: Patients with rheumatoid arthritis (RA) should start treatment early with the aim of suppressing the inflammatory process completely. It is not known if this strategy should, or can, be continued in later disease. METHODS: In a multicentre, randomized, observer-blinded, controlled trial, 466 patients with established RA (>5 yr), on stable therapy for at least 6 months, were randomized to adequate symptom control/shared care setting (SCSC) or aggressive treatment/hospital setting (ATH). All were reviewed annually by a rheumatologist. The primary outcome after 3 yr was the Health Assessment Questionnaire (HAQ). Others included the OMERACT core set and the Disease Activity Score (DAS) 28. RESULTS: Three hundred and ninety-nine patients completed the trial. There was a significant deterioration in HAQ in both arms. Only the physician global score differed between the arms. CONCLUSIONS: The trial showed no additional benefit of intensified treatment with traditional disease modifying anti-rheumatic drugs (DMARDs) in patients with stable, established RA. It proved hard to suppress C-reactive protein levels. Patients in the SCSC arm were able to initiate treatment changes when their symptoms deteriorated without frequent hospital assessment. Pending further evidence, the model of shared care with annual hospital review is as good as 4-monthly hospital review for these patients.
18825393 [Rehabilitation and outpatient physiotherapy in rheumatic disease patients. Results of cro 2008 Nov Rehabilitation and outpatient physiotherapy were investigated from the perspectives of patients suffering from rheumatoid arthritis (RA) or ankylosing spondylitis (AS) and of rheumatologists. In 2007, 204 outpatients with RA and 47 with AS at the Arthritis Center in Halle, Germany, and 117 rheumatologists from all over the country participated in two questionnaire surveys. Patients and rheumatologists gave predominantly positive judgements of physiotherapy, psychological interventions, and patient education programs. However, outpatient care including these interventions was judged to be mainly limited by fixed budgets and other formal restrictions. Even though these therapeutic options are part of (primarily inpatient) rehabilitation programs, the estimate of the need for multidisciplinary rehabilitation programs varied widely among the rheumatologists. Significant objections against rehabilitation include reluctance of the patients, administrative burden for the physicians, payers' rejections, and limited choice of rehabilitation clinic. Despite major functional limitations, a substantial portion of the patients received no multidisciplinary medical rehabilitation, outpatient physiotherapy, psychological interventions, or patient education. Recommendations for the improvement of care are derived from these data.
17678825 Electronic and computer-generated patient questionnaires in standard care. 2007 Aug Patient-derived measures of disease activity have been proven to be reliable, valid, sensitive to change, and less susceptible to placebo effects in the assessment of many rheumatic diseases. Traditionally, paper forms have been used to capture this information but with advances in technology and a growing number of computer users, computerized versions have been developed. The computerized patient-derived questionnaires have been shown to be valid and reliable in many studies. Despite a concern for the usability and acceptability among inexperienced computer users and certain subgroups, such as older persons, a majority of patients queried preferred the electronic versions and found them easy to use. In addition, these computerized versions offer several advantages over the paper format, including improved data capture with less ambiguity, less long-term cost, immediate scoring and availability of the results, and--most importantly--the ability for more frequent disease activity, efficacy, and safety assessments.
18986531 Impact of low-dose prednisolone on bone synthesis and resorption in early rheumatoid arthr 2008 INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased frequency of osteoporosis, mainly because of increased bone resorption. Reduction of disease activity is suggested to reduce bone remodelling. It might also be possible that prednisolone treatment could cause this effect because prednisolone has been shown to arrest the development of joint destruction in early RA. Therefore, we examined the effects of low-dose prednisolone on serum concentrations of bone remodelling markers and insulin-like growth factor-1 (IGF-1) in RA patients in relation to bone mineral density. METHODS: One hundred and fifty patients, 67% women, with early RA, mean disease duration of six months (95% confidence interval (CI) = three to eight months), who had participated in the BARFOT (Better Anti-Rheumatic FarmacOTherapy) low-dose prednisolone study were included. They had been randomised to either the P-group, who were treated with 7.5 mg prednisolone daily (n = 70, mean age = 51 years, 95% CI 48 to 54 years), or the NoP-group, who received no prednisolone (n = 80, mean age 58 years, 95% CI 56 to 61 years), when they started their first disease-modifying anti-rheumatic drug (DMARD). Serum samples were analysed at baseline, 3 and 12 months for procollagen type I N-terminal propeptide (P1NP), a marker of bone formation, and the C-telopeptide crosslaps of type I collagen (CTX-1) and C-terminal telopeptide of type I collagen (1CTP), markers of bone degradation. IGF-1 was analysed at baseline and after 12 months. Bone mineral density at the lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry at baseline and after 24 months. RESULTS: Levels of P1NP decreased rapidly in the P-group (p < 0.001). Levels of CTX-1 and 1CTP decreased in both treatment groups, but significantly more in the P-group (differences between groups p < 0.019 and p < 0.001, respectively). IGF-1 increased in the P-group (p < 0.001) but remained stable in the NoP-group. Bone mineral density decreased in the spine in both groups, significantly more in postmenopausal women from the P-group. Femur bone mineral density only decreased in the NoP-group. CONCLUSIONS: Low-dose prednisolone in early RA counteracts the negative impact of rheumatoid inflammation on bone tissue in the hip, a juxta-articular localisation. Thus bone mineral density was preserved in the femur in the P-group and 1CTP decreased rapidly. However, the systemic inflammatory consequences on bone could not be prevented in the lumbar spine, especially not in postmenopausal women, probably because of the combined effect of suppression of bone synthesis by prednisolone and the postmenopausal status.
17951654 Laser capture as a tool for analysis of gene expression in inflamed synovium. 2007 Most current approaches used to analyze gene expression in tissue samples are based on RNA isolated either from cultured synovial cells or from synovial biopsies. However, this strategy does not distinguish between specific gene expression profiles of cells originating from discrete tissue areas. Therefore, we established the combination of laser-mediated microdissection and RNA arbitrarily primed polymerase chain reaction (RAP-PCR) for differential display to analyze profiles of gene expression in histologically defined areas of arthritic tissue. Cryosections derived from synovial tissue were used to obtain cell samples from different tissue areas of both rheumatoid arthritis (RA) and osteoarthritis (OA) patients using a microbeam laser microscope. RNA was isolated and analyzed using nested RNA arbitrarily primed PCR to generate a fingerprint of the expressed gene sequences. Differentially expressed bands were isolated, cloned, and sequenced. Differential expression of identified sequences was confirmed by in situ hybridization and immunohistochemistry.
17094002 Efficacy of computer-assisted pedicle screw insertion for cervical instability in RA patie 2007 Apr We evaluated the efficacy of the computer-assisted cervical pedicle screw insertion, compared with those inserted without the help of the system on the cervix of rheumatoid arthritis (RA) patients. Eighty-six cervical pedicle screws were inserted without the help of the system. Of the 86, 59 screws were in non-RA patients with degenerative spine, and 27 were in RA patients. The accuracy of the screw insertions was evaluated by a CT-based method. Then, 25 screws were inserted with the system into the cervical spines between C2 and C6 in RA patients (Navigation group). The efficacy of the system was assessed by the CT-based method, compared with 27 screws inserted without the system (Conventional group). The screws in RA patients tended to be more deviated than those in non-RA patients. In Conventional group, four screws (15%) were placed far laterally, and two (7%), far medially. In contrast, no screw was placed far laterally or medially in Navigation group (P < 0.05).
16680389 Ethnicity may be a reason for lipid changes and high Lp(a) levels in rheumatoid arthritis. 2007 Mar There are so many studies that suggest the changes in lipid profiles and lipoprotein (a) [Lp(a)] are associated with early atherosclerosis in rheumatoid arthritis (RA). But there are some opposite studies also. Because of marked ethnicity differences in the distribution of Lp(a), we aimed to investigate the associations of Lp(a) levels and lipid changes in Turkish RA patients. There were 30 women and 20 men, a total of 50 patients with RA (mean age 47.6 +/- 13.2 years), included and 21 healthy women and 14 healthy men (mean age 45.7 +/- 14.5 years) were recruited as a control (C) group. Serum Lp(a), total cholesterol (TC), triglyceride (TG), HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels were analysed for each group. Analysis of six different studies was performed. In the RA and C groups, mean serum Lp(a) levels were 39.7 +/- 64.4 and 10.5 +/- 13.4 mg/dl, respectively (P=0.001). Mean TC levels were 189.2 +/- 142.5 and 174.0 +/- 29.3 mg/dl (P=0.294), mean TG levels were 121.4 +/- 65.4 and 106.5 +/- 80.0 mg/dl (P=0.030), mean HDL-C levels were 44.5 +/- 10.0 and 47.7 +/- 4.8 mg/dl (P=0.014) and mean LDL-C levels were 94.3 +/- 35.3 and 102.0 +/- 24.6 mg/dl (P=0.98), respectively. Analysis of the six studies showed Lp(a) level was higher and HDL level was lower in RA patients than in healthy controls. Patients with RA may have altered lipid profiles from one country to another one. Especially in Turkey, higher serum Lp(a), lower HDL-C and higher TG levels may be found in RA patients instead of some findings of other countries showing different results. Ethnicity may be a reason for these findings.
18042642 Responsiveness to anti-tumour necrosis factor alpha therapy is related to pre-treatment ti 2008 Apr OBJECTIVE: The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor alpha (TNFalpha) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab. METHODS: Synovial biopsies were obtained by arthroscopy from 18 RA patients with active disease (28 joint count Disease Activity Score (DAS28) > or = 3.2) before initiation of treatment with infliximab. All patients were on stable methotrexate treatment. Clinical response at 16 weeks was defined as a reduction in DAS28 of > or = 1.2, non-response as reduction in DAS28 < 1.2. Large-scale gene expression profiling using microarrays was performed on synovial tissue samples. To identify biological processes in synovial biopsies that could discriminate between responders and non-responders, we performed pathway analysis on the expression profiles. RESULTS: A total of 12 patients responded to therapy, while 6 patients failed to fulfil the response criteria. We identified several biological processes, related to inflammation, which were up-regulated in patients who responded to therapy, compared to those who did not show clinical improvement. CONCLUSION: These results indicate that patients with a high level of tissue inflammation are more likely to benefit from anti-TNFalpha treatment.
17288585 Protein, iron, and meat consumption and risk for rheumatoid arthritis: a prospective cohor 2007 A recent prospective study showed that higher consumption of red meat and total protein was associated with increased risk for inflammatory polyarthritis. We therefore prospectively examined the relationship between diet (in particular, protein, iron, and corresponding food sources) and incident rheumatoid arthritis (RA) among 82,063 women in the Nurses' Health Study. From 1980 to 2002, 546 incident cases of RA were confirmed by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria for RA. Diet was assessed at baseline in 1980 and five additional times during follow up. We conducted Cox proportional hazards analyses to calculate the rate ratio of RA associated with intakes of protein (total, animal, and vegetable) and iron (total, dietary, from supplements, and heme iron) and their primary food sources, adjusting for age, smoking, body mass index, and reproductive factors. The multivariate models revealed no association between RA and any measure of protein or iron intake. In comparisons of highest with lowest quintiles of intake, the rate ratio for total protein was 1.17 (95% confidence interval 0.89-1.54; P for trend = 0.11) and for total iron it was 1.04 (95% confidence interval 0.77-1.41; P for trend = 0.82). Red meat, poultry, and fish were also not associated with RA risk. We were unable to confirm that there is an association between protein or meat and risk for RA in this large female cohort. Iron was also not associated with RA in this cohort.
18060342 Histological changes in bone marrow after treatment of infliximab for rheumatoid arthritis 2008 Apr To investigate histological evidence of bone remodeling in response to infliximab for rheumatoid arthritis (RA), bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty after treatment of infliximab for an average of 16 months (range, 8-24 months). The patients had a mean age of 65.3 years (range, 57-76 years) with 4.8 mg/week of methotrexate (MTX; 4-6 mg) and 3.8 mg/day of prednisolone (2-5 mg). Control samples were obtained from ten RA patients who did not undergo infliximab therapy. These patients had an average age of 67.6 years (range, 59-78 years) and received 5.2 mg/week of MTX (4-6 mg) and 4.0 mg/day of prednisolone (2-5 mg). Histological examination of structural differences between the infliximab and control groups in bone marrow was performed using hematoxylin and eosin (H & E) to evaluate differences. In immunohistochemical examination, the expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), receptor activator of nuclear (kappa) B ligand (RANKL), osteoprotegerin (OPG), and osteopontin (OPN) were compared between both groups. H & E staining revealed that the bone marrow tissues of the RA patients who underwent infliximab therapy demonstrated newly formed thickness of interstitial septum among the trabeculae as compared with the control group. Moreover, immunohistochemical examinations revealed that TNF-alpha, IL-6, RANKL, OPG, and OPN were expressed in this newly formed bone after infliximab therapy. Therefore, treatment with infliximab improved the histological changes with respect to bone metabolism in the newly formed bone marrow tissues.
16948115 IgG and IgM anticardiolipin antibodies following treatment with infliximab plus methotrexa 2006 Sep OBJECTIVE: To assess the occurrence of anticardiolipin antibodies (aCL) in patients with early rheumatoid arthritis (RA) receiving treatment with infliximab plus methotrexate (MTX) versus MTX alone. METHODS: The first 299 patients enrolled in the randomized, Active-Controlled Study of Patients Receiving Infliximab for the Treatment of Rheumatoid Arthritis of Early Onset (ASPIRE) trial who had baseline (week 0) samples available for aCL testing were included in this study. Sera were collected at weeks 0, 30, and 54 from 110 patients taking infliximab 3 mg/kg plus MTX, 98 patients taking infliximab 6 mg/kg plus MTX, and 91 patients taking placebo plus MTX. IgG and IgM aCL were measured using an anticardiolipin assay. RESULTS: IgG and IgM aCL positivity at baseline was similar in all treatment groups. Most patients were negative for IgG aCL at baseline and remained so at the last followup evaluation. One percent (2 of 208) of patients who received infliximab plus MTX and were negative for IgG aCL at baseline were positive for IgG aCL at weeks 30 and 54. A slightly higher proportion of patients who received infliximab plus MTX and were negative for IgM aCL at baseline were positive for IgM aCL at weeks 30 and 54 (4.8% [10 of 208]) as compared with patients who received placebo plus MTX (1.1% [1 of 91]), but the difference was not significant. CONCLUSION: There was a low incidence of the development of aCL in patients with early RA who received infliximab in combination with MTX, and the difference was not significant compared with patients who received placebo plus MTX.
16569263 Immune complexes from rheumatoid arthritis synovial fluid induce FcgammaRIIa dependent and 2006 Immune complexes (ICs) can induce production of cytokines by peripheral blood mononuclear cells via Fc receptors. Rheumatoid factor (RF) develop in response to ICs in many clinical and experimental settings. We investigated whether and how polyethylene glycol (PEG) precipitated ICs from rheumatoid arthritis (RA) sera and synovial fluid (SF) can influence cytokine production by peripheral blood mononuclear cells. We also examined the relationship between RF and IC induced cytokine production. Parallel sera and SF from 47 RA patients and sera from 15 healthy control individuals were PEG precipitated. The precipitates were added to serum-free peripheral blood mononuclear cell cultures and tumour necrosis factor (TNF)-alpha levels were measured after 20 hours. In separate cell culture experiments FcgammaRIIa and FcgammaRIII were blocked and monocytes were depleted or enriched. RF in serum was determined by nephelometry, and IgG levels in precipitates and anti-cyclic citrullinated peptide antibodies in serum were measured using ELISA. Clinical data were collected from the patients' charts. In two separate investigations, we demonstrated a correlation between RF, PEG-precipitated IgG levels and induction of the proinflammatory cytokine TNF-alpha by PEG-precipitated SF ICs. No such correlation was found for serum ICs. TNF-alpha levels induced by SF precipitates, but not serum precipitates, correlated with the number of swollen and tender joints. Monocytes/macrophages were shown to be the main responder cells, and blockade of FcgammaRIIa, but not blockade of FcgammaRIII, inhibited TNF-alpha production in cultures stimulated with precipitated ICs. Anti-cyclic citrullinated peptide correlated with RF but exhibited no association with IgG content in PEG precipitates or with precipitate-induced TNF-alpha levels. These findings support the hypothesis that SF ICs and correlated RF production are directly linked to cytokine-dependent inflammation in RA. Suppression of monocytes/macrophages in RA joints or blockade of the primate-specific activating FcgammaRIIa receptor might be ways to reduce IC-induced TNF-alpha production in the joints of seropositive RA patients.
17094944 Midkine as a molecular target: comparison of effects of chondroitin sulfate E and siRNA. 2006 Dec 29 Intraperitoneally administered chondroitin sulfate E inhibited the development of antibody-induced arthritis, a model of rheumatoid arthritis, while chondroitin 4-sulfate showed no effects. Chondroitin sulfate E inhibited in vitro differentiation of osteoclasts, which play key roles in the etiology of rheumatoid arthritis. One of the targets of chondroitin sulfate E is midkine, a heparin-binding growth factor or cytokine. Indeed, a chimeric-type siRNA for midkine inhibited the development of antibody-induced arthritis and adhesion of the omentum to the injured abdominal wall. These results indicate the significance of midkine as a molecular target to treat or prevent rheumatoid arthritis and adhesion after surgery, and the utility of chondroitin sulfate E to inhibit midkine in vivo.
16489709 Increased expression of surfactant protein A and D in rheumatoid arthritic synovial fluid 2006 Feb AIM: To determine the concentrations of surfactant protein (SP)-A and SP-D in synovial fluid samples from patients with rheumatoid arthritis and healthy controls and correlate them with rheumatoid factor, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, and IgG, total protein, and total lipid content. METHODS: The concentrations of SP-A, SP-D, CRP, IgA, IgM, IgG, and rheumatoid factor were measured in the synovial fluid of 7 patients with rheumatoid arthritis and 3 samples of healthy synovial fluid obtained at autopsy. The bands obtained by specific antibodies in Western blotting to determine the surfactant protein concentration were analyzed densitometrically and synovial fluid total phospholipids and protein content were analyzed spectrophotometrically. RESULTS: Patients with rheumatoid arthritis had increased concentrations of proteins and lipids in the synovial fluid, which correlated with 3.5-fold increase in SP-A and 6.1-fold increase in SP-D concentrations. Total protein content in synovial fluid samples from patients with rheumatoid arthritis showed a 2.1-fold increase and phospholipid content showed 7.0-fold increase in comparison with samples of healthy synovial fluid. Rheumatoid factor, CRP, IgA, IgM, and IgG concentrations in synovial fluid samples from patients with rheumatoid arthritis were 40-2660 KIU/L, 4-35 mg/L, 0.10-2.70 g/L, 0.50-1.90 g/L, and 5.3-15.4 g/L respectively. CONCLUSION: SP-A and SP-D were present and expressed in various degrees in the synovial fluid of patients with rheumatoid arthritis. SP-A and SP-D may play role in the initiation of immune system and joint inflammation, and may be an integral component of synovial fluid and provide insights for in innate and adaptive immunity within the joint.
17195209 New humanized HLA-DR4-transgenic mice that mimic the sex bias of rheumatoid arthritis. 2007 Jan OBJECTIVE: To generate a mouse model that can mimic human rheumatoid arthritis (RA). A major difference between RA in humans and collagen-induced arthritis (CIA) in mice is the lack of sex bias and autoantibodies in the animal model. We used DRB1*0401-transgenic mice to understand the role of DR4 in susceptibility and sex bias in RA. METHODS: A transgenic mouse was generated that lacked all endogenous mouse class II genes (AE(o)) and expressed the RA susceptibility allele HLA-DRB1*0401. These transgenic mice were tested for incidence, severity, and sex distribution of CIA. RESULTS: DRB1*0401.AE(o) mice developed CIA predominantly in females and produced rheumatoid factors, similar to the features of human RA. Another feature similar to human RA is the expression of class II molecules on antigen-presenting cells as well as T cells. Activated and sorted CD4(+) T cells can present DR4-restricted type II collagen (CII)-derived peptide in vitro, but cannot process the antigen. This suggests a role for these cells in epitope presentation locally in joints, which affects disease severity. After challenge with CII, female mice had higher cellularity and increased T cell proliferation and produced higher levels of proinflammatory cytokines than did the male mice. CONCLUSION: DR4.AE(o) mice expressed HLA similar to humans and displayed increased arthritis susceptibility in females, thus mimicking RA in humans. This model may be valuable for studying sex differences observed in humans and for understanding why autoimmunity is increased in women. These mice may also be useful for developing future therapeutic strategies.
18707846 Inflammatory and prothrombotic biomarkers in patients with rheumatoid arthritis: effects o 2008 Sep OBJECTIVE: Increased cardiovascular (CV) risk is a rheumatoid arthritis (RA) hallmark and it has been mainly related to chronic systemic inflammation. Since inflammation is linked to coagulation perturbation, both may play a role in increasing CV risk. Treatment with tumor necrosis factor (TNF)-alpha blocking agents is effective in RA and reduces local and systemic inflammation but there is little information on its effect on coagulation. We therefore investigated inflammation and coagulation plasma biomarkers before and after infliximab treatment in RA patients. METHODS: We studied 20 patients with active RA and 40 healthy controls. Patients were treated with: a stable dose of methotrexate (10mg/week), and infliximab (3mg/kg) at weeks 0, 2, 6 and 14. At baseline and week 14, we determined: disease activity score (DAS-28), visual analogue scale pain, erythrocyte sedimentation rate (ESR), and plasma levels of C-reactive protein (CRP), TNF-alpha, interleukin (IL)-6, prothrombin fragment 1+2 (F1+2) and D-dimer. The same inflammation and coagulation parameters were evaluated 1h after infliximab infusion in 10 patients. RESULTS: At baseline, ESR, CRP, TNF-alpha, IL-6, F1+2 and D-dimer levels were significantly higher in RA patients than in controls (P=0.0001). After 14weeks of infliximab treatment, there was a significant clinical improvement and ESR and CRP, IL-6, F1+2 and D-dimer level decrease (P=0.001-P=0.008). The levels of TNF-alpha, IL-6, F1+2 and D-dimer significantly decreased 1h after infliximab infusion (P=0.005). CONCLUSIONS: Infliximab decreases inflammation and coagulation biomarkers in RA patients. Such a combined effect may be pivotal in reducing the whole thrombotic risk in these patients.
17454848 Short-term effects of the TNFalpha antagonist infliximab on the acute phase reaction and a 2007 OBJECTIVE: To investigate the short-term effects of the tumour necrosis factor alpha (TNFalpha) antagonist infliximab on the acute phase reaction and activities of daily life (ADL) in patients with rheumatoid arthritis (RA). METHODS: Fourteen patients with active RA were treated with an intravenous infusion of 200 mg infliximab. The values of the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, granulocyte count, lymphocyte count, platelet count and a patient questionnaire score on ADL, the Health Assessment Questionnaire (HAQ), were obtained at baseline and on days 4 and 14. The significance levels and effect sizes (ESs) of the changes from baseline were calculated. RESULTS: Changes by day 4: The ESs and significance levels were: CRP 1.7, p<0.005; lymphocyte count 1.4, p<0.005; fibrinogen 0.9, p<0.005; ESR 0.7, p<0.005; and HAQ 0.6, p<0.01. Changes by day 14: CRP 1.6, p<0.005; ESR 1.5, p<0.005; fibrinogen 1.3, p<0.005; lymphocyte count 1.0, p<0.005; granulocyte count 0.7, p<0.05; and HAQ 0.6, p<0.05. CONCLUSION: CRP, fibrinogen and ESR showed the largest ESs and were thus the most sensitive variables showing the early effect of infliximab in this study. The score on ADL (HAQ) showed less ES, but still significant short-term improvements.