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

ID PMID Title PublicationDate abstract
21598617 [Adhesive properties of microorganisms colonizing rheumatoid arthritis and systemic lupus 2011 Mar AIM: Evaluation of adhesive properties of microorganisms colonizing rheumatoid arthritis and systemic lupus erythematosus patients. MATERIALS AND METHODS: Nose mucosa and urinal microflora from 62 rheumatoid patients (32--rheumatoid arthritis and 30--systemic lupus erythematosus patients) was studied. 57 opportunistic microorganisms were isolated: including representatives of Staphylococcus, Escherichia, Klebsiella, Morganella, Enterobactergenera. Adhesive properties on erythrocyte model of microorganisms isolated in patients with rheumatoid disease, museum cultures and clinical strains were analyzed by using standard technique. RESULTS: Bacteria isolated in rheumatoid disease patients were characterized by pronounced adhesive potential. Bacteria of Enterobacteriaceae family have shown significantly higher adhesive properties. Heterogeneity of adhesive properties levels, and genera and species adhesive potential of bacteria was determined. CONCLUSION: Microorganisms colonizing rheumatoid disease patients have a high adhesive potential that can increase the risk of patient infections.
21863270 A case of rheumatoid meningitis: pathologic and magnetic resonance imaging findings. 2011 Dec Central nervous system (CNS) involvement is extremely rare in patients with rheumatoid arthritis (RA). Additionally, most patients with CNS involvement have chronic and severe RA. We present a report of a 66-year-old man who was diagnosed with rheumatoid meningitis and CNS vasculitis without a history of RA. His initial symptom was seizure. Brain magnetic resonance imaging showed leptomeningeal enhancement.CSF analysis revealed slight increase in the number of white blood cells. An examination of viral markers and culture studies for infectious etiology were unremarkable. However, the rheumatoid factor was positive and the levels of anti-cyclic citrullinated peptide antibody were very high. The patient was diagnosed with rheumatoid meningitis and received steroid therapy. However, he developed CNS vasculitis. We suggested that the possibility of rheumatoid meningitis should be considered during the differential diagnosis stage in patients with uncontrolled meningitis, even though RA does not typically show CNS involvement.
22480507 Partial extensor carpi radialis longus turn-over tendon transfer for reconstruction of the 2012 Jun Reconstruction of a distally ruptured extensor pollicis longus tendon in the rheumatoid patient generally involves a tendon transfer or intercalary graft. We present an alternative technique using the radial half of the extensor carpi radialis longus as a turn-over graft. Using the turn-over technique with a half-slip of the extensor carpi radialis longus avoids the traditional limitations of the extensor carpi radialis longus tendon in distal extensor pollicis longus tendon repairs and precludes the need for a free tendon graft.
21279466 A pilot study on zinc levels in patients with rheumatoid arthritis. 2011 Nov The aim of the study was to evaluate zinc levels in three biological compartments (serum, erythrocytes and hair) in patients with rheumatoid arthritis (RA) as compared to healthy individuals. Zinc levels in serum, erythrocytes and hair (in 74 patients with RA and 30 healthy individuals) were assessed by atomic absorption spectroscopy. The mean hair zinc content was significantly lower in RA patients as compared to healthy individuals (p<0.001). Moreover, a positive correlation was observed in the RA patient group between the erythrocyte zinc levels and the prednisone dose (rs=0.48, p<0.05), and a negative correlation was found in this population between the serum zinc levels and disease duration (rs=-0.42, p<0.0006). In conclusion, it seems that hair may be a useful complementary study material for evaluating "zinc status" in rheumatoid arthritis patients.
22532640 A systematic literature review of strategies promoting early referral and reducing delays 2013 Jan BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.
22890524 [Laboratory diagnostics for early detection of rheumatic autoimmune diseases: a guide for 2012 Nov Autoimmune diseases are a clinically heterogeneous group of disorders that represent a challenge for the general practitioner in daily routine. Except for rheumatoid arthritis, which is one of the most frequent autoimmune diseases with a prevalence of approximately 1 % of the population, systemic autoimmune disorders are rare. Thus outside specialized wards it might be a challenge to diagnose the underlying autoimmune disease considering the often kaleidoscopic clinical manifestations. Together with careful anamnesis and suspicious clinical symptoms determination of specific autoantibodies can support the suspected diagnosis. The Austrian group of the European autoimmune standardization initiative (EASI) firstly published this guide 2009 with the aim to provide a map through the jungle of the biomarkers for autoimmune diseases for the general practitioner.
21841782 A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheuma 2011 Aug 14 A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies.
22073934 Assessment of disease activity and treatment outcomes in rheumatoid arthritis. 2011 Nov BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease which primarily causes a symmetric polyarthritis. Clinical manifestations of the disease include joint pain, stiffness, and swelling. Unless treated, this debilitating disease can progress into long-term disability. Medications for RA include synthetic disease-modifying antirheumatic drugs (DMARDs) and biologic agents. The rapid expansion of new RA drugs into the market has led to a need for health care practitioners to understand the effectiveness of each medication and the indications of use including when to initiate and stop therapies. Clinical assessment tools, including biomarkers used to indicate RA and the progression of the disease, have been proven effective for making a diagnosis and determining effective treatment regimens. Disease activity scales are also useful for guiding diagnoses and monitoring patients to assess treatment effectiveness. OBJECTIVES: To review the various clinical assessment tools that have been designed to confirm an early diagnosis of RA, measure disease progression, and assist in determining the most optimal treatment regimens for patients with RA. SUMMARY: The diagnosis of RA combines the patient history of joint pain and stiffness and the physical examination documentation of symmetric polyarticular joint swelling (synovitis). Laboratory tests including radiographs and blood tests for biomarkers can provide useful information to confirm the diagnosis of RA. Various autoantibodies have been reported in the blood of RA patients, but only the rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) have been incorporated as diagnostic measures in routine clinical practice. Monitoring and assessment instruments for RA include the Disease Activity Score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Although these clinical assessment tools have limitations, health care providers can use them as measures of disease progression and to assist in planning treatment strategies to modify disease activity and improve the quality of life for the patient.
21961333 [Current methods of systemic amyloidosis diagnosis and monitoring of its course]. 2011 AIM: To determine clinical significance of measuring blood levels of protein precursors of AA- and AL-amyloidosis - SAA and immunoglobulin free light chains (ILC), respectively. MATERIAL AND METHODS: SAA concentrations were studied with ELISA in 43 rheumatoid arthritis (RA) patients including complicated with reactive AA-amyloidosis (n = 31). Inflammation activity and its severity were studied (indices Li, richi, HAQ, DAS4). A modern quantitative nephelometric method Freelite estimated ILC levels in 31 patients with AL-amyloidosis. RESULTS: Patients with RA complicated with AA-amyloidosis and free of it had a strong correlation between blood serum SAA concentration and activity of joint disease. Elevated SAA concentrations to 160 mg/l (normal 10 mg/l) were detected in many patients with clinical remission of the joint syndrome. Significal inhibition of AA-amyloidosis progression was seen only in SAA concentration drop under 60 mg/l. For AL-amyloidosis patients ILC fall by less than 3 normal value means a 6-time increase in chances of a favourable outcome. CONCLUSION: Monitoring of blood levels of proteins precursors of AA- and AL-amyloidosis is a key factor in prognosis of the disease and treatment efficacy.
21622769 Diagnostic performance of the ACR/EULAR 2010 criteria for rheumatoid arthritis and two dia 2011 Sep INTRODUCTION: An ACR/EULAR task force released new criteria to classify rheumatoid arthritis at an early stage. This study evaluates the diagnostic performance of these criteria and algorithms by van der Helm and Visser in REACH. METHODS: Patients with symptoms ≤12 months from REACH were used. Algorithms were tested on discrimination, calibration and diagnostic accuracy of proposed cut-points. Two patient sets were defined to test robustness; undifferentiated arthritis (UA) (n=231) and all patients including those without synovitis (n=513). The outcomes evaluated were methotrexate use and persistent disease at 12 months. RESULTS: In UA patients all algorithms had good areas under the curve 0.79, 95% CI 0.73 to 0.83 for the ACR/EULAR criteria, 0.80, 95% CI 0.74 to 0.87 for van der Helm and 0.83, 95% CI 0.77 to 0.88 for Visser. All calibrated well. Sensitivity and specificity were 0.74 and 0.66 for the ACR/EULAR criteria, 0.1 and 1.0 for van der Helm and 0.59 and 0.93 for Visser. Similar results were found in all patients indicating robustness. CONCLUSION: The ACR/EULAR 2010 criteria showed good diagnostic properties in an early arthritis cohort reflecting daily practice, as did the van der Helm and Visser algorithms. All were robust. To promote uniformity and comparability the ACR/EULAR 2010 criteria should be used in future diagnostic studies.
22766304 Carotid arterial stiffness in patients with rheumatoid arthritis assessed by speckle track 2012 Sep OBJECTIVES: Although a series of trials support the intima-media thickness (IMT) of carotid artery as a good predictor for the cardiovascular events in patients with rheumatoid arthritis (RA), the link between IMT, vascular elastic property and the disease activity of RA is not defined. We investigated the association between carotid atherosclerosis, elastic properties of the carotid arterial wall and clinical parameters of RA. METHODS: One hundred and twenty RA patients and fifty healthy controls were included. Peak systolic global circumferential and posterior radial strain of carotid artery were measured to assess the elastic properties. Beta stiffness index was used as conventional method for the distensibility of the carotid artery. RA activity was assessed by high sensitivity C-reactive protein (hsCRP) and disease activity score with 28 joints (DAS 28) and health assessment questionnaire (HAQ). RESULTS: Carotid plaques were more common in RA patients. RA patients with plaques were older and had an increased mean IMT, hsCRP, DAS 28, and longer disease duration compared with those without plaques. Peak systolic global circumferential and posterior radial strain were congruent with β stiffness index, and significantly lower in the RA group. Age, disease duration, hsCRP, DAS 28 showed significant correlations with mean IMT and parameters of carotid elastic property. CONCLUSIONS: Carotid atherosclerosis was more common in RA patients, and carotid arterial stiffness had significant correlation with disease duration and disease activity of RA. Speckle tracking strain imaging is a comparative method for the assessment of elastic properties of carotid artery of RA patients.
21640040 Burden of depressive symptoms in South African public healthcare patients with established 2011 May OBJECTIVES: The burden of depressive symptoms and how demographic and disease characteristics relate to depressive symptoms in patients with rheumatoid arthritis (RA) that belong to developing populations, are currently unknown and were therefore assessed in a case-control study in public healthcare patients in South Africa, a lower-middle income country. Public healthcare attendance is a surrogate of belonging to the developing population in South Africa. METHODS: Demographic and RA features were recorded in 441 public and 202 private healthcare patients. The outcome characteristic was the Arthritis Impact Measure Scales (AIMS) depression score. Relationships of patient characteristics and public healthcare attendance with depressive symptoms were determined in multivariable regression models. RESULTS: The mean ± SD AIMS depression score was 3.6±2.1 and 2.3±1.7 in public and private healthcare patients, respectively (p<0.0001 before and after adjustment for covariates). Physical disability was associated with depressive symptoms in both healthcare sectors. Other characteristics that were related to depressive symptoms comprised younger age, male sex and pain in public healthcare patients and fatigue and non-use of disease modifying agents in private healthcare patients. In all patients, public healthcare attendance (standardised ß [95% CI]=0.22 [0.12, 0.32], p<0.0001) and physical disability (standardised β [95% CI]=0.25 [0.16, 0.34], p<0.0001) were most strongly associated with depressive symptoms. CONCLUSIONS: The burden of depressive symptoms is markedly enhanced in our developing population with RA, independent of age, sex, ethnic origin and disease characteristics. In this setting, the role of social factors should be assessed and, despite restricted resources, depressive symptoms should be routinely addressed.
22596166 Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in 2012 Oct OBJECTIVES: To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA) patient population from the computer assisted management in early rheumatoid arthritis (CAMERA) study. METHODS: Twenty biomarkers were measured in the CAMERA cohort, in which patients were treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA score was calculated using the concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained algorithm. The performance of the scores was evaluated relative to clinical disease activity assessments. Change in MBDA score over time was assessed by paired Wilcoxon rank sum test. Logistic regression was used to evaluate the ability of disease activity measures to predict radiographic progression. RESULTS: The MBDA score had a significant correlation with the disease activity score based on 28 joints-C reactive protein (DAS28-CRP) (r=0.72; p<0.001) and an area under the receiver operating characteristic curve for distinguishing remission/low from moderate/high disease activity of 0.86 (p<0.001) using a DAS28-CRP cut-off of 2.7. In multivariate analysis the MBDA score, but not CRP, was an independent predictor of disease activity measures. Additionally, mean (SD) MBDA score decreased from 53 (18) at baseline to 39 (16) at 6 months in response to study therapy (p<0.0001). Neither MBDA score nor clinical variables were predictive of radiographic progression. CONCLUSIONS: This multi-biomarker test performed well in the assessment of disease activity in RA patients in the CAMERA study. Upon further validation, this test could be used to complement currently available disease activity measures and improve patient care and outcomes.
21770041 Relationship between early bone mineral density changes and long-term function and radiogr 2012 Jan OBJECTIVE: To ascertain whether bone mineral density loss during the first year of treatment for early rheumatoid arthritis (RA) as assessed by dual x-ray absorptiometry (DXA) is associated with long-term function, quality of life, and radiographic progression. METHODS: Early RA patients, prior to commencing disease-modifying antirheumatic drug therapy, underwent evaluation with DXA scans of both hands, femoral neck, and lumbar spine at the time of diagnosis, then at 1 year and final followup at >6 years. Clinical and laboratory data and hands and feet radiographs were obtained at baseline and final followup. RESULTS: Sixty-four patients were assessed. At baseline, median disease duration was 6 months, mean 28-joint Disease Activity Score was 5.85, and median Health Assessment Questionnaire score was 1.38. Median followup was 6.4 years (range 5.1-7.2 years). For erosion scores, 86% of patients with hand bone density loss above the smallest detectable change after 1 year progressed versus 55% of those with no hand bone density loss (P = 0.006). However, baseline radiographs showed a similar strength of association. Eighty-four percent of patients with erosions at baseline had erosion progression versus 57% of those with no baseline erosions (P = 0.021). Additionally, first-year bone density loss was not associated with function and quality of life status at followup. CONCLUSION: Hand bone loss during the first year of treatment in early RA, as assessed with DXA, was associated with a high likelihood of radiographic progression; however, in the current study this was not superior to baseline radiographs. Furthermore, it was not associated with patient-reported outcomes.
23028356 Functional variants in NFKBIE and RTKN2 involved in activation of the NF-κB pathway are a 2012 Sep Rheumatoid arthritis is an autoimmune disease with a complex etiology, leading to inflammation of synovial tissue and joint destruction. Through a genome-wide association study (GWAS) and two replication studies in the Japanese population (7,907 cases and 35,362 controls), we identified two gene loci associated with rheumatoid arthritis susceptibility (NFKBIE at 6p21.1, rs2233434, odds ratio (OR) = 1.20, P = 1.3 × 10(-15); RTKN2 at 10q21.2, rs3125734, OR = 1.20, P = 4.6 × 10(-9)). In addition to two functional non-synonymous SNPs in NFKBIE, we identified candidate causal SNPs with regulatory potential in NFKBIE and RTKN2 gene regions by integrating in silico analysis using public genome databases and subsequent in vitro analysis. Both of these genes are known to regulate the NF-κB pathway, and the risk alleles of the genes were implicated in the enhancement of NF-κB activity in our analyses. These results suggest that the NF-κB pathway plays a role in pathogenesis and would be a rational target for treatment of rheumatoid arthritis.
22546912 [Biomarkers in rheumatology. Biomarkers and imaging for the diagnosis and stratification o 2012 Jun The introduction of biologics has continuously increased the demand for biomarkers for early diagnosis and therapeutic stratification. ArthroMark, a research network funded by the Federal Ministry of Education and Research, aims to establish such biomarkers for rheumatoid arthritis and spondyloarthritides. Biobanks and previous work on genotyping, gene expression and autoreactivity profiling build the basis. Bioinformatic networks will help to harmonize the investigations and a clinical study with modern imaging techniques to characterize the functional relevance of the new biomarkers as effectively as possible. To validate the markers for diagnostic application the network aims to expand gradually.
23104728 Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthr 2014 Sep Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed. Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals. CONCLUSION: Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA.
22607179 Autoimmunity in focus: from mechanisms to treatment. 2012 May The 5th Asian Congress on Autoimmunity took place in Suntec City, Singapore, on the 17-19 November 2011 under the presidency of Yehuda Shoenfeld (Chaim Sheba Medical Center, Ramat Gan, Israel). Senior investigators from a range of fields--including immunology, autoimmunity, rheumatology, neurology and hepatology--attended the conference. The scientific program placed an emphasis on the pathogenesis, genetic basis and mechanistic aspects of autoimmune diseases, as well as their clinical outcomes and treatment options. Particular focus was placed on systemic lupus erythematosus, rheumatoid arthritis, Type I diabetes, antiphospholipid syndrome and autoimmune hepatitis. Participants from over 50 countries attended the conference.
22878986 Diffuse alveolar haemorrhage in granulomatosis with polyangitis (Wegener's) with coexisten 2012 Aug 8 Diffuse alveolar haemorrhage is a serious manifestation of granulomatosis with polyangitis (Wegener's) with high morbidity and mortality. It is defined by the clinical triad of haemoptysis, anaemia and progressive hypoxaemia. The diagnosis of granulomatosis with polyangitis is confirmed in an appropriate clinical setting by bronchoalveolar lavage, lung biopsy or detection of C-antineutrophil cytoplasmic antibodies. In this report, the patient was a known case of rheumatoid arthritis and presented with diffuse alveolar haemorrhage on CT scan; the underlying cause was found to be granulomatosis with polyangitis (Wegener's) with positive C-antineutrophil cytoplasmic antibodies. Despite aggressive treatment with immunosuppressants and steroids the patient died within a few days.
21149499 Smoking is a major preventable risk factor for rheumatoid arthritis: estimations of risks 2011 Mar BACKGROUND: Earlier studies have demonstrated that smoking and genetic risk factors interact in providing an increased risk of rheumatoid arthritis (RA). Less is known on how smoking contributes to RA in the context of genetic variability, and what proportion of RA may be caused by smoking. OBJECTIVES: To determine the association between the amount of smoking and risk of RA in the context of different HLA-DRB1 shared epitope (SE) alleles, and to estimate proportions of RA cases attributed to smoking. DESIGN: Setting and Participants Data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study encompassing 1204 cases and 871 controls were analysed. Main Outcome Measure Estimated OR to develop RA and excess fraction of cases attributable to smoking according to the amount of smoking and genotype. RESULTS: Smoking was estimated to be responsible for 35% of anticitrullinated protein/peptide antibody (ACPA)-positive cases. For each HLA-DRB1 SE genotype, smoking was dose-dependently associated with an increased risk of ACPA-positive RA (p trend <0.001). In individuals carrying two copies of the HLA-DRB1 SE, 55% of ACPA-positive RA was attributable to smoking. CONCLUSIONS: Smoking is a preventable risk factor for RA. The increased risk due to smoking is dependent on the amount of smoking and genotype.