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

ID PMID Title PublicationDate abstract
22584415 The role of adipokines in connective tissue diseases. 2012 Aug OBJECTIVE: To discuss the relationship between adipokines and connective tissue diseases, by putting special emphasis on the potential role of leptin, adiponectin, resistin, and other adipose tissue products in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus and on possible application of adipokine-targeted therapy in the treatment of these disorders with emphasis on the recent findings. METHODS: PubMed literature search complemented by review of bibliographies listed in identified articles. RESULTS: Most of the data presented by different research groups showed changed levels of leptin, adiponectin, and resistin and occasionally also other adipokines in rheumatoid arthritis and systemic lupus erythematosus. The relationship between the remaining connective tissue diseases and adipokines is less documented. CONCLUSIONS: Plasma levels of adipokines might tell us too little about their role in connective tissue disorders, whereas adipokine effects on synovial tissues might differ from their known metabolic or cardiovascular effects, which implies that some re-appraisal of adipokines role may need to take place. It still remains obscure whether the observed disturbances in various adipokine systems in subjects with connective tissue diseases contribute to their development or only reflect the presence or activity of inflammatory process, which itself is induced by other pro-inflammatory factors.
23217568 Gender differences in Latin-American patients with rheumatoid arthritis. 2012 Dec BACKGROUND: Data on the effect of gender in rheumatoid arthritis (RA) in non-Caucasian populations is scarce. Latin America and the Caribbean (LAC) is a large population with unique characteristics, including high admixture. OBJECTIVE: Our aim was to examine the effect of gender in patients with RA in LAC. METHODS: This was a 2-phase study. First we conducted a cross-sectional and analytical study in which 1128 consecutive Colombian patients with RA were assessed. Second, a systematic review of the literature was done to evaluate the effect of gender in LAC patients with RA. RESULTS: Our results show a high prevalence of RA in LAC women with a ratio of 5.2 women per man. Colombian women with RA are more at risk of having an early age at onset and developing polyautoimmunity and abdominal obesity, and they perform more household duties than their male counterparts. However, male gender was associated with the presence of extra-articular manifestations. Of a total of 641 potentially relevant articles, 38 were considered for final analysis, in which several factors and outcomes related to gender were identified. CONCLUSIONS: RA in LAC women is not only more common but presents with some clinical characteristics that differ from RA presentation in men. Some of those characteristics could explain the high rates of disability and worse prognosis observed in women with RA in LAC.
22075375 Therapeutic effect of Yunnan Baiyao on rheumatoid arthritis was partially due to regulatin 2012 Feb 5 In order to explore the potential therapeutic effect of Yunnan Baiyao (YNB) on rheumatoid arthritis (RA), rat models were constructed and orally administrated with YNB or methotrexate (MTX) in parallel. Clinical physical, histological and biochemical parameters showed trivial therapeutic difference between YNB and MTX applications. Urine and serum metabonomics results indicated that many endogenous metabolites differentially changed among the rats receiving diverse therapeutic interventions. Among them, the fluctuation of arachidonic acid (AA) was thought to make sense. Thus, its relevant metabolites were subjected to quantitation by using osteoblasts treated by YNB in vitro. It was found that YNB extract of 20 μg/mL could greatly activate the synthesis of intracellular prostaglandin E₂ and thromboxane B₂ in osteoblasts. Excretion of prostaglandin D₂ could be suppressed but not the thromboxane B₂. This study proved the efficacy of YNB on curing RA and its potential mechanism through modulating AA metabolism in osteoblasts to some extent.
21586211 Association study of 3 rheumatoid arthritis risk loci in systemic sclerosis in European Ca 2011 Mar INTRODUCTION: Accumulating evidences show that shared autoimmunity is critical for the pathogenesis of many inflammatory rheumatic conditions. Specific phenotype could arise from specific genes, and/or combination of genetic factors and environment. Systemic sclerosis (SSc) belongs to connective tissue disorders and recent data have highlighted strong associations with some autoimmunity genes shared with other autoimmune diseases. OBJECTIVES: To determine whether novel risk loci associated with rheumatoid arthritis (RA) may confer susceptibility to SSc. Single nucleotide polymorphism from CCL21, CD244 and CDK6 were tested for association. METHODS: SNPs harbouring association with RA, CCL21-rs2812378, CDK6-rs42041 and CD244-rs6682654 were genotyped in a cohort of 1031 SSc patients and 1014 controls. All individuals were of European Caucasian origin. RESULTS: The three polymorphisms were in Hardy-Weinberg equilibrium in the control population and allelic frequencies were similar to those expected in European populations. Allelic and genotypic frequencies for these three polymorphisms were found to be similar in SSc patients and controls. Moreover, sub-phenotype analyses in particular for subgroups having diffuse subcutaneous subtype, specific auto-antibodies or fibrosing alveolitis did not detect any difference between SSc patients and controls. CONCLUSIONS: These results obtained through a large cohort of European Caucasian SSc patients do not support the implication of CCL21, CD244 and CDK6 genes in the pathogenesis of SSc although these genes were recently identified as RA susceptibility genes.
21777703 B-cells and their targeting in rheumatoid arthritis--current concepts and future perspecti 2011 Nov Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects primarily the joints and without proper treatment results in their progressive destruction. In addition to T-cells, B-cells play a central role in the pathogenesis of this disease. The synovial tissue is an active site of B-cell accumulation, plasma cell differentiation and in situ antibody-production in RA. As part of the complex role of B-cells in the joints and synovial membrane of RA patients, B cells secrete chemokines and cytokines and may function as antigen presenting cells. The multifaceted pathogenic function of B-cells identifies them as excellent targets for immunosuppressive therapy. B-cell targeting involves a wide spectrum of molecules, for example the B-cell antigen CD20 that allows specific and effective B-cell depletion. Another target, CD79, expressed by B-cell and plasma cell precursors is an obvious candidate that induces apoptosis as well as inhibition of B-cell receptor (BCR) activation and possibly depletion of ectopic germinal centers (GC). Inhibition of B-cell co-stimulatory molecules such as CD40, CD80/86 and ICOS, can lead to diminished B-cell activation. Moreover, anti-chemokine and anti-cytokine therapies can be efficacious in RA by the disruption of B-cell activation and autoantibody production, B-cell synovial migration and ectopic GC formation. Finally, targeting the signal transduction pathways required for proximal BCR signaling has also been found efficacious in early clinical trials in RA. Even so, some B cells inhibit immune responses, these regulatory B cells may play a part in immune regulation in patients and it is unclear what effects B cell depletion strategies have in terms of such B cell subsets. This review discusses current strategies of targeting B-cells as therapeutic candidates in the management of RA. Better insights into the pathogenic role of B-cells provide efficacious opportunities to improve both therapy and prognosis of patients with RA.
20814812 Immunochemical studies on catechol-estrogen modified plasmid: possible role in rheumatoid 2011 Feb INTRODUCTION: Increased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive. METHODS: The binding of antibodies from the sera of RA patients and control subjects to native and modified DNA was studied by direct binding and inhibition ELISA, quantitative precipitin titration. Experimentally induced antibodies were also checked to detect oxidative lesions in the DNA as well as for the estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in different fluids of RA. RESULTS: Anti-DNA IgG from RA sera, exhibited increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The relative affinity of anti-DNA antibodies for modified and nDNA was in the order of 1.85 × 10(-7), 1.23 × 10(-7), and 1.2 × 10(-6). Samples of DNA from RA patients showed a significant inhibition in the induced antibody activity in comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG evaluated by induced antibody in RA patients was found to be significantly higher than controls ((P < 0.0001, P < 0.01, P < 0.05). CONCLUSION: High binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.
23249339 Reliability and responsiveness of dynamic contrast-enhanced magnetic resonance imaging in 2013 OBJECTIVES: To investigate the responsiveness to treatment and the reliability of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rheumatoid arthritis (RA) knee joints. METHODS: DCE-MRI was performed in 12 clinically active RA knee joints before and 1, 7, 30, and 180 days after intra-articular injection with 80 mg methylprednisolone. Using semi-automated image processing software, DCE-MRI parameters, including the initial rate of enhancement (IRE) and maximal enhancement (ME), were generated for three regions of interest (ROIs): 'Whole slice', 'Quick ROI', and 'Precise ROI'. The smallest detectable difference (SDD), the smallest detectable change (SDC), and intra- and inter-reader intraclass correlation coefficients (ICCs) were used to assess the reliability of DCE-MRI. Responsiveness to treatment was assessed by the standardized response mean (SRM). RESULTS: In all patients clinical remission of the knee was achieved at day 7. All DCE-MRI parameters decreased from day 0 to day 7. Using the Quick and Precise ROI methods, respectively, IRE decreased by 63% and 69%, ME decreased by 11% and 11%, N decreased by 55% and 57%, and IRE × N decreased by 84% and 85%. The intra- and inter-reader ICCs were very high (0.96-1.00). The decrease in DCE-MRI parameters was larger than the SDC for all patients. SRM was large for all parameters, ranging from -1.04 to -2.40. When the Whole slice ROI method was used, no parameters were responsive to treatment. CONCLUSIONS: DCE-MRI analysed using semi-automatic software is a reliable and responsive tool for assessing treatment in RA knees joints. Rough manual delineation of the joint to omit enhancement artefacts is necessary.
22195070 Naïve Electronic Health Record phenotype identification for Rheumatoid arthritis. 2011 Electronic Health Records (EHRs) provide a real-world patient cohort for clinical and genomic research. Phenotype identification using informatics algorithms has been shown to replicate known genetic associations found in clinical trials and observational cohorts. However, development of accurate phenotype identification methods can be challenging, requiring significant time and effort. We applied Support Vector Machines (SVMs) to both naïve (i.e., non-curated) and expert-defined collections of EHR features to identify Rheumatoid Arthritis cases using billing codes, medication exposures, and natural language processing-derived concepts. SVMs trained on naïve and expert-defined data outperformed an existing deterministic algorithm; the best performing naïve system had precision of 0.94 and recall of 0.87, compared to precision of 0.75 and recall of 0.51 for the deterministic algorithm. We show that with an expert defined feature set as few as 50-100 training samples are required. This study demonstrates that SVMs operating on non-curated sets of attributes can accurately identify cases from an EHR.
22371298 Importance of patient history and physical examination in rheumatoid arthritis compared to 2012 Aug OBJECTIVE: To survey physicians' opinions concerning the relative importance of 5 clinical encounter components-vital signs, patient history, physical examination, laboratory tests, and ancillary studies-in the diagnosis and management of 8 chronic diseases. METHODS: A SurveyMonkey internet survey was e-mailed to 7,265 US physicians, including 3,542 rheumatologists and 3,723 nonrheumatologists, with the following query: "Please indicate the relative importance of 5 sources of information-vital signs, patient history, physical examination, laboratory tests, and ancillary studies-in diagnosis of congestive heart failure (CHF), diabetes mellitus, hypercholesterolemia, hypertension, lymphoma, pulmonary fibrosis, rheumatoid arthritis (RA), and ulcerative colitis." The response options were 0-20%, 21-40%, 41-60%, 61-80%, and 81-100%. A second query with an identical structure addressed management of the 8 diseases. The proportions of physicians who estimated each component as most (or tied for most) important in diagnosis or in management were computed. RESULTS: The survey was completed by 313 physicians (154 rheumatologists and 159 nonrheumatologists). More than 90% estimated vital signs as most important for hypertension, and laboratory tests for diabetes mellitus and hypercholesterolemia. More than 70% estimated ancillary studies as most important for lymphoma, pulmonary fibrosis, and ulcerative colitis. Patient history and physical examination were estimated as most important for RA and CHF by ≥50% of nonrheumatologists. CONCLUSION: RA and CHF were the only 2 of the 8 diseases studied for which ≥50% of nonrheumatologists estimated a patient history and physical examination as most important for diagnosis and management. Confirmation and extension of these observations in actual care may have implications for reimbursement and organization of clinical care.
23207283 Immunogenicity and autoimmunity during anti-TNF therapy. 2013 May The introduction of anti-tumour necrosis factor (TNF) agents for the treatment of rheumatoid arthritis (RA), Crohn's disease (CD) or spondyloarthritis (SpA) has revolutionised the therapeutic approach to patients with active disease failing to respond to conventional therapy. However, some of the patients treated with selective TNF inhibitors may develop autoantibodies, such as antinuclear antibodies (ANAs) and anti-double-stranded DNA (anti-dsDNA) antibodies. Furthermore, anti-phospholipid antibodies, which are mainly detected by means of anti-cardiolipin assays, have been found in RA patients receiving TNF blockers. There have also been a number of reports of the development of anti-drug antibodies, of which those against infliximab can interfere with the drug's pharmacokinetics (and therefore its effects), and may also cause acute and delayed infusion and injection site reactions. The onset of autoimmune diseases during biological treatment is rare, but it needs to be promptly recognised in order to plan appropriate patient management. The addition of an immunosuppressive drug can reduce the induction of anti-TNF antibodies.
22749530 Sjögren's syndrome at the crossroad of polyautoimmunity. 2012 Sep The coexistence of autoimmune diseases (i.e., polyautoimmunity) in Sjögren's syndrome (SS) was investigated in a cross-sectional study involving 410 patients. Logistic regression analysis and the Rogers and Tanimoto index were used to evaluate risk factors and clustering, respectively. There were 134 (32.6%) patients with polyautoimmunity. The most frequent and closer coexistent diseases were autoimmune thyroid disease (21.5%), rheumatoid arthritis (8.3%), systemic lupus erythematosus (7.6%), and inflammatory bowel disease (0.7%) which together constituted a cluster group. There were 35 (8.5%) patients with multiple autoimmune syndrome. Besides disease duration, a history of habitual smoking and spontaneous abortion were found to be risk factors for the developing of polyautoimmunity. This study discloses a high prevalence of polyautoimmunity in SS, its associated risk factors and the grouping pattern of such a condition. These results may serve to define plausible approaches to study the common mechanisms of autoimmune diseases.
21876977 A close association of body cell mass loss with disease activity and disability in Chinese 2011 OBJECTIVES: To investigate the association of body cell mass loss with disease activity and disability in rheumatoid arthritis patients. INTRODUCTION: Rheumatoid cachexia, defined as the loss of body cell mass, is important but under-recognized and contributes to morbidity and mortality in patients with rheumatoid arthritis. METHODS: One hundred forty-nine rheumatoid arthritis patients and 53 healthy, non-rheumatoid arthritis control subjects underwent anthropometric measurements of body mass index and waist and hip circumferences. Bioelectrical impedance analysis was used to determine the subjects' body compositions, including fat mass, skeletal lean mass, and body cell mass. The disease activity of rheumatoid arthritis was assessed using C-reactive protein serum, the erythrocyte sedimentation rate and the 28-joint disease activity score, while disability was evaluated using a health assessment questionnaire. RESULTS: Rheumatoid arthritis patients had lower waist-to-hip ratio (0.86 ± 0.07 vs. 0.95 ± 0.06; p<0.001) and lower skeletal lean mass indexes (14.44 ± 1.52 vs. 15.18 ± 1.35; p = 0.002) than those in the healthy control group. Compared with rheumatoid arthritis patients with higher body cell masses, those with body cell masses lower than median had higher erythrocyte sedimentation rates (40.10 ± 27.33 vs. 25.09 ± 14.85; p<0.001), higher disease activity scores (5.36 ± 3.79 vs. 4.23 ± 1.21; p = 0.022) and greater disability as measured by health assessment questionnaire scores (1.26 ± 0.79 vs. 0.87 ± 0.79; p = 0.004). CONCLUSIONS: The loss of body cell mass is associated with higher disease activity and greater disability in rheumatoid arthritis patients. Body composition determined by bioelectrical impedance analysis can provide valuable information for a rheumatologist to more rapidly recognize rheumatoid cachexia in rheumatoid arthritis patients.
22366735 Involvement of mitogen-activated protein kinases and peroxisome proliferator-activated rec 2012 May To investigate whether monosodium urate (MSU) crystals could induce the production of VCAM-1 (vascular cell adhesion molecule 1) in human synovial cells and its possible signaling pathways, human synovial cells isolated from synovial tissue explants were stimulated with various doses of MSU crystals for different time intervals. Expression of VCAM-1 was evaluated with Western blotting. To explore the underlying mechanisms, VCAM-1 protein expression was also evaluated after activation of several signaling molecules including mitogen-activated protein kinases (MAPKs) and peroxisome proliferator-activated receptor γ (PPARγ) were blocked. Exposure of synovial cells to MSU crystals induced VCAM-1 expression in culture medium in a dose- and time-dependent manner, reaching a plateau at 1000 µM and 24 h. Inhibition of the activation of MAPKs and PPARγ could block this increase. The present results demonstrated that MSU crystals could induce VCAM-1 expression. MAPKs and PPARγ signaling pathways regulated the induced VCAM-1 expression.
21486513 Vitamin B6: a challenging link between nutrition and inflammation in CVD. 2011 Jul The objective of the present review is to highlight the relationship between low vitamin B6 status and CVD through its link with inflammation. While overt vitamin B6 deficiency is uncommon in clinical practice, increasing evidence suggests that marginal vitamin B6 deficiency is rather frequent in a consistent proportion of the population and is related to an increased risk of inflammation-related diseases. Ample evidence substantiates the theory of atherosclerosis as an inflammatory disease, and low plasma vitamin B6 concentrations have been related to increased CVD risk. Several studies have also shown that low vitamin B6 status is associated with rheumatoid arthritis and chronic inflammatory bowel diseases, both of which hold an underlying chronic inflammatory condition. Furthermore, the inverse association observed between inflammation markers and vitamin B6 supports the notion that inflammation may represent the common link between low vitamin B6 status and CVD risk. In addition to the epidemiological evidence, there are a number of cell culture and animal studies that have suggested several possible mechanisms relating impaired vitamin B6 status with chronic inflammation. A mild vitamin B6 deficiency characterises, in most cases, a subclinical at-risk condition in inflammatory-linked diseases which should be addressed by an appropriate individually tailored nutritional preventive or therapeutic strategy.
21789568 Protective effect of Withania somnifera and Cardiospermum halicacabum extracts against col 2011 Oct The irreversible destruction of extracellular matrix (ECM) such as cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis and osteoarthritis by over-expression of matrix metalloproteinase (MMP)-collagenases. We report herein the detailed study on the inhibitory effects of Withania somnifera extract (WSE) and Cardiospermum halicacabum extract (CHE) on Clostridium histolyticum collagenase (ChC) activity against the degradation of the ECM component of bovine Achilles tendon type I collagen by hydroxyproline assay method. Interaction of WSE and CHE with ChC exhibited 71% and 88% inhibition, respectively, to the collagenolytic activity of ChC against collagen degradation, and the inhibition was found to be concentration-dependent. The inhibition kinetics of ChC by both the extracts has been deduced from the extent of hydrolysis of N-[3-(2-furyl) acryloyl]-Leu-Gly-Pro-Ala. Both WSE and CHE are provided competitive and mixed type inhibition on ChC activity, respectively. Circular dichroism studies of ChC on treatment with WSE and CHE revealed changes in the secondary structure of collagenase. These results suggest that the WSE and CHE facilitated collagen stabilization through collagenase inhibition.
21959042 Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis. 2011 INTRODUCTION: Chemerin is a chemotactic agonist identified as a ligand for ChemR23 that is expressed on macrophages and dendritic cells (DCs). In this study, we analyzed the expression of chemerin and ChemR23 in the synovium of rheumatoid arthritis (RA) patients and the stimulatory effects of chemerin on fibroblast-like synoviocytes (FLSs) from RA patients. METHODS: Chemerin and ChemR23 expression in the RA synovium was ascertained by immunohistochemistry and Western blot analysis. Chemerin expression on cultured FLSs was analyzed by ELISA. ChemR23 expression on FLSs was determined by immunocytochemistry and Western blot analysis. Cytokine production from FLSs was measured by ELISA. FLS cell motility was evaluated by utilizing a scrape motility assay. We also examined the stimulating effect of chemerin on the phosphorylation of mitogen-activated protein kinase (MAPK), p44/42 mitogen-activated protein kinase (ERK1/2), p38MAPK, c-Jun N-terminal kinase (JNK)1/2 and Akt, as well as on the degradation of regulator of NF-κB (IκBα) in FLSs, by Western blot analysis. RESULTS: Chemerin was expressed on endothelial cells and synovial lining and sublining cells. ChemR23 was expressed on macrophages, immature DCs and FLSs and a few mature DCs in the RA synovium. Chemerin and ChemR23 were highly expressed in the RA synovium compared with osteoarthritis. Chemerin and ChemR23 were expressed on unstimulated FLSs. TNF-α and IFN-γ upregulated chemerin production. Chemerin enhanced the production of IL-6, chemokine (C-C motif) ligand 2 and matrix metalloproteinase 3 by FLSs, as well as increasing FLS motility. The stimulatory effects of chemerin on FLSs were mediated by activation of ERK1/2, p38MAPK and Akt, but not by JNK1/2. Degradation of IκB in FLSs was not promoted by chemerin stimulation. Inhibition of the ERK1/2, p38MAPK and Akt signaling pathways significantly suppressed chemerin-induced IL-6 production. Moreover, blockade of the p38MAPK and Akt pathways, but not the ERK1/2 pathway, inhibited chemerin-enhanced cell motility. CONCLUSIONS: The interaction of chemerin and ChemR23 may play an important role in the pathogenesis of RA through the activation of FLSs.
21765109 Canadian recommendations for clinical trials of pharmacologic interventions in rheumatoid 2011 Oct OBJECTIVE: Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials. METHODS: Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process. RESULTS: Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension. CONCLUSION: There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.
23013849 Wait times for rheumatology consultation: is rheumatoid arthritis prioritized? 2012 Oct OBJECTIVES: Patients with rheumatoid arthritis (RA) should be seen by a rheumatologist promptly; however, there are no recommendations for patients with osteoarthritis (OA). Our goal was to describe wait times from referral by the primary care provider to rheumatology consultation and to explore whether wait times are associated with type of arthritis diagnosis, geographic area, or type of rheumatology office. METHODS: Appointments were requested by telephone using case scenarios that were created by a group of experts and included (1) presumed RA, (2) possible RA, and (3) presumed OA. Wait times were evaluated as the time between the initial request and the appointment date provided. We used descriptive statistics, bivariate analysis, and logistic regression in the analysis. RESULTS: For all scenarios combined, 34% were given an appointment with a rheumatologist within 3 months of referral, 32% waited longer than 3 months, and 34% were told that the rheumatologist was not accepting new referrals at the time the request was made. Patients with presumed RA were much more likely to be seen within 3 months of referral compared with those with presumed OA (odds ratio, 13; 95% confidence interval, 1.70-99.38). CONCLUSIONS: Rheumatoid arthritis is prioritized over OA for rheumatology appointments. However, most patients with RA are still not receiving an appointment to a rheumatologist in a timely manner. Effective triage tools to decrease these delays should be instituted.
21696620 Correlation between endothelial function and carotid atherosclerosis in rheumatoid arthrit 2011 Jun 22 INTRODUCTION: In this study, we aimed to determine the relationship between flow-mediated endothelium-dependent vasodilatation (FMD) and carotid artery intima-media wall thickness (IMT), two surrogate markers of atherosclerosis, in a series of Spanish patients with rheumatoid arthritis (RA) without clinically evident cardiovascular (CV) disease. METHODS: One hundred eighteen patients who fulfilled the 1987 American College of Rheumatology classification criteria for RA, had no history of CV disease and had at least one year of follow-up after disease diagnosis were randomly selected. Brachial and carotid ultrasonography were performed to determine FMD and carotid IMT, respectively. RESULTS: Carotid IMT values were higher and FMD percentages derived by performing ultrasonography were lower in individuals with a long duration from the time of disease diagnosis. Patients with a disease duration ≤ 7 years had significantly lower carotid IMT (mean ± SD) 0.69 ± 0.17 mm than those with long disease duration (0.81 ± 0.12 mm in patients with ≥ 20 years of follow-up). Also, patients with a long disease duration had severe endothelial dysfunction (FMD 4.0 ± 4.0% in patients with disease duration from 14.5 to 19.7 years) compared with those with shorter disease duration (FMD 7.4 ± 3.8% in patients with disease duration ≤ 7 years). Linear regression analysis revealed that carotid IMT was unrelated to FMD in the whole sample of 118 patients. However, carotid IMT was negatively associated with FMD when the time from disease diagnosis ranged from 7.5 to 19.7 years (P = 0.02). CONCLUSIONS: In patients with RA without CV disease, endothelial dysfunction and carotid IMT increased with the duration of RA. The association between FMD and carotid IMT values was observed only in patients with long disease duration.
22528482 Heavy chains of inter alpha inhibitor (IαI) inhibit the human complement system at early 2012 Jun 8 Inter alpha inhibitor (IαI) is an abundant serum protein consisting of three polypeptides: two heavy chains (HC1 and HC2) and bikunin, a broad-specificity Kunitz-type proteinase inhibitor. The complex is covalently held together by chondroitin sulfate but during inflammation IαI may interact with TNF-stimulated gene 6 protein (TSG-6), which supports transesterification of heavy chains to hyaluronan. Recently, IαI was shown to inhibit mouse complement in vivo and to protect from complement-mediated lung injury but the mechanism of such activity was not elucidated. Using human serum depleted from IαI, we found that IαI is not an essential human complement inhibitor as was reported for mice and that such serum has unaltered hemolytic activity. However, purified human IαI inhibited classical, lectin and alternative complement pathways in vitro when added in excess to human serum. The inhibitory activity was dependent on heavy chains but not bikunin and detected at the level of initiating molecules (MBL, properdin) in the lectin/alternative pathways or C4b in the classical pathway. Furthermore, IαI affected formation and assembly of the C1 complex and prevented assembly of the classical pathway C3-convertase. Presence and putative interactions with TSG-6 did not affect the ability of IαI to inhibit complement thus implicating IαI as a potentially important complement inhibitor once enriched onto hyaluronan moieties in the course of local inflammatory processes. In support of this, we found a correlation between IαI/HC-containing proteins and hemolytic activity of synovial fluid from patients suffering from rheumatoid arthritis.