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ID PMID Title PublicationDate abstract
15800005 A comparison of the diagnostic accuracy and prognostic value of the first and second anti- 2005 Oct OBJECTIVES: To compare the diagnostic performance and prognostic value of the anti-cyclic citrullinated peptide (CCP1) and anti-CCP2 autoantibody tests in a clinical setting. METHODS: Anti-CCP1 and anti-CCP2 antibody tests were performed on the same serum samples obtained from 467 patients with early arthritis from the Leiden Arthritis Cohort. The sensitivity, specificity, positive predictive value, and negative predictive value for discriminating between rheumatoid arthritis (RA) and non-RA at 1 year's follow up were calculated for both tests. Results were graphically presented using receiver operating characteristic curves. Progression of radiological joint damage was assessed over 4 years in patients with RA and used to assess the prognostics values of the CCP tests. RESULTS: At a similar specificity the CCP2 test had a higher sensitivity than the CCP1 test. Both tests identified a subgroup of patients with RA with an increased rate of joint damage progression. The anti-CCP2 test identified more patients with an increased rate of joint damage progression than the anti-CCP1 test, and in multiple regression analysis CCP2 was the better predictor of joint damage. CONCLUSIONS: The CCP2 test had better diagnostic and prognostic ability than the CCP1 test.
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.
15868630 Determinants of treatment adherence in ethnically diverse, economically disadvantaged pati 2005 May OBJECTIVE: To explore the determinants of adherence to medical recommendations, including drug therapy and appointment-keeping, among ethnically diverse and economically disadvantaged patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: Patients with RA and SLE were identified through chart review and were invited to participate in focus groups to examine their attitudes and beliefs regarding adherence to treatment and medical appointments. Eight focus groups (4 RA, 4 SLE) were conducted, with a total of 40 participants (22 SLE patients and 18 RA patients). Transcripts were analyzed using grounded theory techniques and qualitative analysis software to facilitate coding interpretation. RESULTS: The majority of participants reported experiencing difficulty in adhering to their treatment at least occasionally. Both SLE and RA patients reported similar barriers to treatment adherence: fear of side effects, financial problems, difficulty in navigating the public health system, and perceived treatment inefficacy. RA and SLE patients also revealed barriers to appointment keeping, including difficulties in scheduling, financial costs, transportation, and functional impairment limiting their ability to attend the clinic. CONCLUSION: Patients' perceptions of and experiences with the health system, physicians, medication effectiveness, and side effects influence their adherence to treatment and other medical recommendations. Strategies to improve adherence could include the following: attempting to modify patients' beliefs and perceptions regarding medication effectiveness, promoting realistic expectations about risk/benefit ratios, and improving access to health care by reducing barriers that limit the interaction between patients and the health system.
16188452 Cytokine medicines in clinical practice: current issues. 2005 Oct 21 Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field.
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.
15751072 Investigation of the SLC22A4 gene (associated with rheumatoid arthritis in a Japanese popu 2005 Mar OBJECTIVE: Recent studies of 2 complex diseases, rheumatoid arthritis (RA) and Crohn's disease (CD), showed associations with genes mapping to the cytokine gene cluster on 5q31. In particular, a functional single-nucleotide polymorphism (SNP) mapping to intron 1 of the organic cation transporter 1 (OCTN1; SLC22A4) gene was associated with RA in a Japanese population, and a haplotype of a different SNP in the same gene and one in an adjacent gene, OCTN2 (SLC22A5), was associated with CD. The purpose of this study was to investigate the association between the OCTN locus and RA in a Caucasian population. METHODS: Association with 11 SNPs spanning the SLC22A4 and SLC22A5 genes, including a putative RA-causing functional polymorphism (rs3792876 [slc2f2]) and a functional haplotype previously associated with CD, was investigated in 909 RA cases and 594 population controls in the UK. Genotyping was performed using 5'-allele discrimination assays. Estimated haplotype frequencies were generated using the expectation-maximization algorithm and were compared between cases and controls. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. We found no evidence for an association between RA and either the SNP (rs3792876 [slc2f2]) or the haplotype previously reported to be associated with RA in a Japanese population. Similarly, no association between RA and the haplotype associated with CD was detected. CONCLUSION: Functional polymorphisms of the OCTN gene locus that have previously been associated with RA and CD were not found to be associated with RA in a UK population. The findings do not provide support for a major role of these genes in the etiology of RA in this population.
16855150 Inflammation and sex hormone metabolism. 2006 Jun The incidence of autoimmune diseases is higher in females than in males. In both sexes, adrenal hormones, that is, glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are inadequately low in patients when compared to healthy controls. Hormonally active androgens are anti-inflammatory, whereas estrogens are pro-inflammatory. Therefore, the mechanisms responsible for the alterations of steroid profiles in inflammation are of major interest. The local metabolism of androgens and estrogens may determine whether a given steroid profile found in a subject's blood results in suppression or promotion of inflammation. The steroid metabolism in mixed synovial cells, fibroblasts, macrophages, and monocytes was assessed. Major focus was on cells from patients with rheumatoid arthritis (RA), while cells from patients with osteoarthritis served as controls. Enzymes directly or indirectly involved in local sex steroid metabolism in RA are: DHEA-sulfatase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and aromatase (CYP19), which are required for the synthesis of sex steroids from precursors, 5alpha-reductase and 16alpha-hydroxylase, which can be involved either in the generation of more active steroids or in the pathways leading to depletion of active hormones, and 3alpha-reductase and 7alpha-hydroxylase (CYP7B), which unidirectionally are involved in the depletion of active hormones. Androgens inhibit aromatization in synovial cells when their concentration is sufficiently high. As large amounts of estrogens are formed in synovial tissue, there may be a relative lack of androgens. Production of 5alpha-reduced androgens should increase the local anti-inflammatory activity; however, it also opens a pathway for the inactivation of androgens. The data discussed here suggest that therapy of RA patients may benefit from the use of nonaromatizable androgens and/or the use of aromatase inhibitors.
15693085 Detection of erosions in the rheumatoid hand; a comparative study of multidetector compute 2005 Feb OBJECTIVE: To compare the detection and scoring of erosions in patients with rheumatoid arthritis (RA) using magnetic resonance (MR) and multidetector helical computerized tomographic (CT) scanning. METHODS: Comparative CT and MR scans of the dominant wrist were obtained from 9 patients with RA and clinical examination was performed to assess disease activity. MR and CT scans were scored for erosions and MR scans for bone edema by 2 radiologists using a validated system. Radiographs of the hands and feet were also scored for erosions using the modified Sharp score. RESULTS: In 117 of 135 (87%) sites there was concordance for erosions between MR and CT scans. At the remaining 18/135 sites (13%), erosions were identified by CT but not MR in 12/135 (9%) and by MR but not CT in 6/135 (4%). Partial volume artefacts on MR images and shifts in slice position were the most common reasons for erosion mismatch between MR and CT. The mean CT bone erosion score was significantly higher than the MR erosion score when individual bony sites were examined (p = 0.024), with the greatest difference being at the metacarpal bases. The total bone erosion score also tended to be higher on CT than MR [median scores of 20 (range 0-66) and 12 (0-51), respectively; p = 0.060]. MR and CT erosion scores correlated strongly with the total Sharp score (r = 0.93, p = 0.0002 and r = 0.94, p = 0.0002, respectively) and with the Disease Activity Score (MR: r = 0.77, p = 0.02; CT: r = 0.71, p = 0.03). CONCLUSION: Most erosions were detected using both modalities, but erosion scores were higher on CT than MR scans, especially at the metacarpal bases. It is possible that small erosions in some regions are more easily detected by CT because of its ability to clearly delineate cortical bony margins.
15879699 Expression of IL-17 homologs and their receptors in the synovial cells of rheumatoid arthr 2005 Apr 30 IL-17 is a major proinflammatory cytokine secreted by activated T-lymphocytes that accumulates in the inflamed joints of rheumatoid arthritis (RA) patients. Additional IL-17-related molecules and their receptors have been discovered and may also contribute to RA pathogenesis. We examined the expression of the prototypic IL-17 (IL-17A) and its homologs, IL-17B-F, by RT-PCR analyses of synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients. We also tested for induction of the IL-17 receptor homologs upon stimulation of the fibroblast-like synoviocytes (FLSs) of RA patients with IL-17. The patients' SFMCs expressed IL-17C, E and F in addition to IL-17A. As in the case of IL-17, IL-15 appears to be the major inducer of these homologs in RA SFMCs. We detected transcripts of IL-17R, as well as those of IL-17RB, C and D, in the FLSs of RA patients. Whereas IL-17R expression increased upon in vitro stimulation with IL-17, expression of IL-17RB, C and D was unchanged. However the possibility of cross-interaction between other IL-17 homologs and receptor isoforms remains to be investigated. Our data suggest that these additional homologs should also be considered as targets for immune modulation in the treatment of RA joint inflammation.
15981085 mRNA quantification of T-bet, GATA-3, IFN-gamma, and IL-4 shows a defective Th1 immune res 2005 May A T helper (Th)1 cytokine profile is predominant in the inflamed synovium of rheumatoid arthritis (RA). Since the situation in the blood is more controversial, we studied the Th1/Th2 balance in the peripheral blood of RA patients using mRNA markers. Total RNA was isolated directly from whole blood from 20 RA patients and 14 healthy controls. T-bet and GATA-3 transcription factors associated with Th1 and Th2 responses respectively, and IFNgamma and IL-4 mRNA levels were measured by real-time PCR. In RA but not in control samples, T-bet mRNA levels correlated positively with IFNgamma mRNA levels, and negatively with CRP levels. Accordingly, RA patients were divided into two groups according to CRP levels. In comparison to RA patients with a low CRP (CRP < 40 mg/l), patients with a high CRP (CRP>or=40 mg/l) had lower IFNgamma/beta-actin, T-bet/beta-actin mRNA levels and T-bet/GATA-3 expression ratios. In conclusion, RA blood cells showed a decreased Th1 situation as indicated by low IFNgamma and T-bet mRNA expression. This pattern was found only in patients with the most active disease.
15769791 The cost of glucocorticoid-associated adverse events in rheumatoid arthritis. 2005 Jun OBJECTIVE: To estimate the costs of glucocorticoid associated adverse events (GAEs) in patients with rheumatoid arthritis (RA). METHODS: We conducted a literature review of studies reporting GAEs in RA patients, and developed a Markov model with the following GAEs: fractures (vertebral, hip, pelvic), hypertension, diabetes, gastrointestinal complications, pneumonia, urinary tract infection, cataract and, in an extended model, myocardial infarction (MI) and stroke. Two-year total costs were calculated using direct medical costs (2001 US dollars [USD]) and by running 10,000 Monte Carlo simulations with probability values randomly selected from the GAE literature. RESULTS: On average, glucocorticoid users spent USD 445 more than non-users, or USD 0.46 for each dollar spent on purchasing the drug. When adding MI and stroke, users spent on average USD 430 more than non-users, or USD 0.44 for each dollar spent on purchasing the drug; this incremental cost ranged from USD 193 to USD 682 if MI and stroke were excluded, respectively. In 70% of the simulations there were more deaths among users than among non-users, in both the model with and without MI and stroke. CONCLUSIONS: Although results varied depending on attributed GAEs, in general glucocorticoid users spent more than non-users on GAE treatment, and had higher mortality. Patients, providers and policy makers should consider these potential costs of GAEs when making treatment decisions.
15953872 Diagnostic performances of anti-cyclic citrullinated peptides antibody and antifilaggrin a 2005 Jun Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method.
16508932 Infliximab treatment maintains employability in patients with early rheumatoid arthritis. 2006 Mar OBJECTIVE: To evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive patients with active early RA were randomly allocated to receive MTX plus placebo or MTX plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. Data for patients younger than age 65 years were included in the analyses. A patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. RESULTS: The change in actual employment was not significantly different between patients receiving MTX plus infliximab and those receiving MTX plus placebo (0.5% versus 1.3%; P > 0.5). However, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving MTX plus infliximab compared with that in the group receiving MTX alone (8% versus 14%; P = 0.05). Patients who were treated with infliximab plus MTX had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; P < 0.001); this likelihood was not significantly greater in patients receiving MTX alone. The proportion of employed patients who lost workdays during the trial was smaller in the MTX plus infliximab group than in the MTX-alone group (P = 0.010). CONCLUSION: The actual employment rates among patients in the 2 treatment groups were not different. However, patients with early RA who were treated with MTX plus infliximab had a higher probability of maintaining their employability compared with those who were treated with MTX alone.
16689999 Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic dise 2006 Epithelial-mesenchymal transition (EMT) is a term applied to the process whereby cells undergo a switch from an epithelial phenotype with tight junctions, lateral, apical, and basal membranes, and lack of mobility into mesenchymal cells that have loose interactions with other cells, are non-polarized, motile and produce an extracellular matrix. The importance of this process was initially recognized from a very early step in embryology, but more recently as a potential mechanism for the progression and spread of epithelial cancers. As the sequence of morphological changes has become understood in molecular terms, diseases characterized by alterations in stromal elements and fibrosis are being considered as examples of EMT. This review will focus on the pathogenetic features of immune-mediated renal disease, systemic sclerosis and rheumatoid arthritis that could be explained by EMT.
15639058 Controlling pain by influencing neurogenic pathways. 2005 Feb Neurogenic inflammation and ensuing pain can be modulated by inhibiting the function of primary afferent neurons. The best studied mechanism to accomplish such inhibition is the opioid system. Under inflammatory conditions, the anterograde axonal transport of opioid receptors from dorsal root ganglia toward the peripheral sensory nerve endings is augmented. The increased number of opioid receptors (among other mechanisms) leads to improved analgesic effects of exogenously administered ligands (eg, morphine) and of endogenous leukocyte-derived opioid peptides (eg, beta-endorphin). A current concept proposes that during inflammatory processes endogenous opioid peptides can be secreted from immunocytes, occupy peripheral opioid receptors on sensory nerve endings, and produce analgesia by inhibiting the excitability of these nerves or the release of proinflammatory neuropeptides. This article focuses on the role of peripheral opioid receptors in pain control and on novel pharmaceutical concepts for the treatment of patients who suffer from rheumatoid arthritis and other inflammatory pain.
16507115 Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arth 2006 Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.
16583470 Paraarticular trabecular bone loss at the ultradistal radius and increased arterial stiffe 2006 Apr OBJECTIVE: We recently reported enhanced arterial thickening in patients with rheumatoid arthritis (RA) and the importance of increased bone resorption in this process. Our aim was to examine whether arterial stiffening, another aspect of atherosclerosis, is also increased in patients with RA, and to determine if it is an important risk factor. METHODS: The subjects were 47 patients with RA and 49 healthy controls, all postmenopausal women. Subjects having risk factors for atherosclerosis were excluded. Femoral-ankle (fa) pulse wave velocity (PWV) and brachial-ankle (ba) PWV were measured in all patients using a waveform analyzer. Bone mineral density (BMD) at the ultradistal radius was assessed by peripheral quantitative computed tomography. Inflammation markers (C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, platelet count) and bone resorption markers (urinary excretion of deoxypyridinoline and N-terminal telopeptide) were also measured. RESULTS: The median values of faPWV and baPWV in RA patients were 1124 cm/s [interquartile range (IQR) 1040-1175] and 1539 cm/s (IQR 1297-1738), respectively, which were significantly greater than the respective values of 982 cm/s (IQR 819-1054; p < 0.001) and 1322 cm/s (IQR 1112-1398; p = 0.004) in controls. In multiple regression analysis, the presence of RA emerged as an independent factor associated with the greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. In RA patients alone, BMD in the trabecular bone component, but not for the total bone (cortical plus trabecular), at the ultradistal radius correlated significantly with both faPWV and baPWV. Multiple regression analysis showed that trabecular BMD at the distal radius was a significant factor independently associated with greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. None of the measured inflammation markers or bone resorption markers correlated with either faPWV or baPWV in patients with RA. CONCLUSION: Patients with RA show increased arterial stiffening, in addition to the arterial thickening we have previously reported, supporting the notion of enhanced atherosclerosis in RA patients. Paraarticular bone loss in the trabecular bone component at the ultradistal radius is a factor significantly associated with increased arterial stiffening in RA patients.