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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
16892791 New-onset rheumatoid arthritis after anthrax vaccination. 2006 Jul BACKGROUND: Anthrax vaccine was licensed in 1970 and is used to protect individuals exposed to biological warfare and those who may come in contact with Bacillus anthracis in infected animals or in laboratory settings. The current adsorbed anthrax vaccine is regarded as effective and safe. Adverse effects reported include fever, chills, myalgia, arthralgia, and nausea. Four cases of rheumatoid arthritis (RA) temporally related to anthrax vaccine have been reported. As the number of administered doses increases, a better understanding of its adverse events profile will be forthcoming. OBJECTIVE: To describe another patient with RA temporally related to anthrax vaccination. METHODS: A 42-year-old man developed bilateral knee stiffness and pain in all the proximal interphalangeal joints 5 days after receiving the first dose of anthrax vaccine. He reported chills, fever, and joint and neck pain, with a tender nodule at the injection site after dose 2. Hours after receiving dose 3 he experienced fever, chills, nausea, vomiting, and neck, hand, and shoulder pain. The vaccination series was terminated after the third dose. RESULTS: Physical examination revealed moderate swelling and tenderness of his bilateral proximal interphalangeal joints. His complete blood cell count was normal; rheumatoid factor level, 198 IU/mL; erythrocyte sedimentation rate, 53 mm/h; antinuclear antibodies, negative; C-reactive protein level, 2.7 mg/L; and anti-cyclic citrullinated peptide antibody level, 168 EU. Radiographs revealed mild degenerative changes in his hands and knees bilaterally. CONCLUSIONS: This case represents a fifth patient with RA temporally related to anthrax vaccine.
17951431 Invasion, stress, and spinal arthritis in cane toads. 2007 Nov 6 The impact of invasive species on biodiversity has attracted considerable study, but impacts of the invasion process on the invaders themselves remain less clear. Invading species encounter conditions different from those in their ancestral habitats and are subject to intense selection for rapid dispersal. The end result may be significant stress on individual organisms, with consequent health problems. Our studies on invasive cane toads in Australia reveal severe spinal arthritis in approximately 10% of large adult toads, associated with the same factors (large body size, frequent movement, and relatively long legs) that have enabled toads to invade so rapidly across the Australian tropics.
16641045 The Rheumatoid Arthritis Quality of Life (RAQoL) for Sweden: adaptation and validation. 2006 Mar OBJECTIVE: To produce and evaluate the official Swedish language version of the Rheumatoid Arthritis Quality of Life instrument (RAQoL). METHODS: The UK RAQoL was translated into Swedish by a bilingual translation panel. A separate lay panel was conducted to consider the appropriateness and comprehensibility of the items in Swedish. Interviews were conducted with 15 Swedish RA patients to assess face and content validity. Responses to a postal survey were used to calculate reproducibility and construct validity. RESULTS: Few difficulties arose in the translation process and the new language version was well received by the lay panel and field-test participants. One hundred and sixty-five RA patients participated in the postal survey (69% female; mean age 62.7 years, SD 11.3, RA duration range 1-62 years). Cronbach's alpha for the Swedish RAQoL was 0.91 and test-retest reliability was 0.95, indicating that the instrument has adequate inter-relatedness of items and very low inherent random measurement error. A high correlation with the Health Assessment Questionnaire (HAQ) was observed; this was expected because RA has significant physical manifestations that are in turn a significant determinant of QoL. The Swedish RAQoL was able to distinguish between patients who differed according to their self-perceived RA severity, general health, and rating of their RA today, in addition to whether or not the patient was experiencing a flare of RA. CONCLUSIONS: The official Swedish RAQoL was well received by RA patients. The psychometric quality of the adapted questionnaire means that it is suitable for inclusion in clinical trials involving patients with RA.
17949887 Increase in systemic vascular resistance during acute mental stress in patients with rheum 2008 Jan Patients with rheumatoid arthritis are at increased risk for myocardial infarction. It has been hypothesized that mental stress-induced cardiovascular reactions may play a role in the triggering of myocardial infarction. Cardiovascular activity was measured during rest, stress, and recovery in rheumatoid arthritis patients with high systemic inflammation (C-reactive protein >8 mg/l), rheumatoid arthritis patients with low systemic inflammation (C-reactive protein
16079168 Orthopaedic surgery of the lower limbs in 49,802 rheumatoid arthritis patients: results fr 2006 Mar OBJECTIVES: To analyse changes in the rates of hospital admission and use of orthopaedic surgery to the lower limbs in Swedish patients with rheumatoid arthritis between 1987 and 2001. METHODS: Data for all rheumatoid patients admitted to hospital between 1987 and 2001 were abstracted from the Swedish National Hospital Discharge Register (SNHDR). The data in the register are collected prospectively, recording all inpatient admissions throughout Sweden. The SNHDR uses the codes for diagnoses at discharge and surgical procedures according to the Swedish version of the International Classification of Diseases (ICD). RESULTS: In all, 49,802 individual patients with rheumatoid arthritis were identified, accounting for 159,888 inpatient visits. Hospital admissions for rheumatoid arthritis decreased by 42% (p<0.001) during the period 1987 to 2001. Twelve per cent of all admissions were for a rheumatoid arthritis related surgical procedure to the lower limbs; those admissions decreased markedly (by 16%) between 1987 and 1996, and by 12% between 1997 and 2001, as did the overall number of rheumatoid arthritis related surgical procedures to the lower limbs during both time periods. Between 1997 and 2001, 47% of all rheumatoid arthritis related surgical procedures were total joint arthroplasties. There was an overall trend towards reduced length of hospital stay after orthopaedic surgery to the lower limbs during the study period. CONCLUSIONS: Rates of hospital admission and rheumatoid arthritis related surgical procedures to the lower limbs in Swedish patients with rheumatoid arthritis decreased between 1987 and 2001. This may reflect trends in disease severity, management, and health outcomes of this disease in Sweden.
17100104 Physical, psychosocial and economic impact of rheumatoid arthritis: a pilot study of patie 2006 Jul BACKGROUND: Rheumatoid arthritis is associated with marked physical disability. In addition, it has an impact on patients' psyche and social well-being, and entails a major financial burden. The impact of the disease in different cultural and social backgrounds is varied. Limited data are available from India on this aspect. METHODS: Patients with rheumatoid arthritis satisfying the 1987 modified American College of Rheumatology criteria were included. Besides demographic data, functional impact was assessed using the Health Assessment Questionnaire (HAQ). The psychosocial impact was measured using the medical outcomes study short form 36 (SF-36) with minor modifications. Data on direct and indirect health costs were collected by direct interview. RESULTS: The mean age of 101 patients (90 women) was 43.2 years and mean duration of disease was 8 years. Their mean (SD) HAQ score was 0.97 (0.69) with 8 patients having scores > 2. On the SF-36 scale (0-100) the mean (SD) score for various domains were: physical functioning 49.90 (28.55), social functioning 55.51 (20.59), role limitation due to physical problems 32.67 (41.34), role limitation due to emotional problems 47.54 (40.08), mental health 47.36 (7.99), general health perception 52.38 (8.30), energy and vitality 58.56 (6.09), and bodily pain 49.26 (18.87). The summary score for the physical component was 37.95 (9.03) and for the mental component it was 47.71 (4.81). While the physical component summary score had excellent negative correlation with the HAQ score (r = -0.84), correlation with the mental component summary score was poor (r = 0.32). The annual average total cost burden per patient was Rs 16 758, of which Rs 11 617 (67%) was spent on health services and the rest on non-health services (travel, home help and loss of wages). CONCLUSION: Rheumatoid arthritis causes significant physical and social disability besides being an economic burden. Indian patients had good scores for mental and social health suggesting good family support systems or reluctance to express their feelings despite physical disability.
17516213 CRP and the disposal of dying cells: consequences for systemic lupus erythematosus and rhe 2007 Jun C reactive protein (CRP) levels directly correlate with the disease activity of many inflammatory diseases, e.g. sepsis, infection, and various autoimmunopathies such as rheumatoid arthritis (RA). In contrast, insufficient CRP levels are implicated in the development of systemic lupus erythematosus (SLE). This article reports on the level-depended effects of CRP in various diseases. In detail we show that increased and decreased levels of CRP, as demonstrated in patients with RA and SLE, respectively can contribute to disease progression.
17763446 Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid ar 2007 Sep OBJECTIVE: To study possible mechanisms that mediate induction of the recently described adipocytokine pre-B cell colony-enhancing factor (PBEF) in joints of patients with rheumatoid arthritis (RA), and to analyze whether levels of PBEF correlate with disease severity and whether PBEF itself has the potential to act as a proinflammatory and destructive mediator in RA. METHODS: RA synovial fibroblasts (RASFs) and monocytes were stimulated with Toll-like receptor (TLR) ligands, cytokines, and recombinant human PBEF or were transfected with PBEF expression constructs or with PBEF-specific small interfering RNA. Production of interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNFalpha) was measured by enzyme-linked immunosorbent assay, and expression of matrix metalloproteinases (MMPs) was assessed by real-time polymerase chain reaction. PBEF expression in synovial tissue, synovial fluid, serum, and SFs was assessed by immunohistochemistry, in situ hybridization, Western blotting, and enzyme immunoassays. RESULTS: In RASFs, PBEF was up-regulated by TLR ligands and cytokines that are characteristically present in the joints of patients with RA. In synovial tissue, RASFs were the major PBEF-expressing cells. A predominance of PBEF was found in the synovial lining layer and at sites of invasion into cartilage. Levels of PBEF in serum and synovial fluid correlated with the degree of inflammation and clinical disease activity. Moreover, PBEF itself activated the transcription factors NF-kB and activator protein 1 and induced IL-6, IL-8, MMP-1, and MMP-3 in RASFs as well as IL-6 and TNFalpha in monocytes. PBEF knockdown in RASFs significantly inhibited basal and TLR ligand-induced production of IL-6, IL-8, MMP-1, and MMP-3. CONCLUSION: Our findings establish PBEF as a proinflammatory and destructive mediator of joint inflammation in RA and identify PBEF as a potential therapeutic target.
19043967 [Pharmacogenomics of methrotexate: a strategy for a customized therapeutic scheme for pati 2008 Sep Rheumatoid arthritis (RA) is a common rheumatic disease in Mexico. Methotrexate (MTX) is a drug frequently used in the treatment of this disease. However, treatment discontinuation due to side effects is also common. Inter-individual differences in effectiveness and occurrence of side effects in RA patients treated with MTX (RA-MTX) have been reported. Several studies analyzed the presence of MTHFR C677T and A1298C polymorphisms in RA-MTX patients associated with effectiveness, side effects and toxicity. Given the high frequency of the MTHFR C677T polymorphism in Mexico, it is of utmost interest to determine the allelic and genotypic frequency of these polymorphisms in patients with RA-MTX. The use of molecular techniques, feasible in our country, such as PCR/RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) can allow us to identify these MTHFR genotypes among RA-MTX patients in order to target patients at risk of developing drug toxicity, side effects or better MTX efficacy. The ultimate goal is to develop individualized treatment, as promised by the field of pharmacogenomics.
17642242 [Monitoring of clinical course in TNF inhibitor treatment for rheumatoid arthritis--effica 2007 Jul Tumor necrosis factor (TNF) inhibitors, such as infliximab (INF) and etanercept (ETA), are highly effective in patients with active rheumatoid arthritis (RA), but have the potential of serious toxicity. For evaluation of treatment with TNF inhibitors, RA patients should be determined for the ACR core set of measures, including tender joint count, swollen joint count, pain score, patient global assessment, physician global assessment, patient-reported functional disability, and acute phase reactants (ESR and CRP), and more practically for the 28-joint Disease Activity Score (DAS28) within the first 3-6 months, and the efficacy could be assessed using the ACR preliminary criteria and the EULAR criteria. Post-marketing surveillance of INF and ETA in Japan indicated that the most serious adverse effects were bacterial pneumonia, pneumocytosis, and interstitial pneumonia, as well as tuberculosis. Infections must be carefully monitored in the patients, particularly those with > or =65 years of age, diabetes, and pulmonary disease. So far no clinical predictors of response to TNF inhibitors have been identified, but genetic variation in the HLA-DRB1 and the LTA-TNF regions was shown to influence the response.
17716614 ABAP: antibody-based assay for peptidylarginine deiminase activity. 2007 Oct 15 Members of the family of peptidylarginine deiminases (PADs, EC 3.5.3.15) catalyze the posttranslational modification of peptidylarginine into peptidylcitrulline. Citrulline-containing epitopes have been shown to be major and specific targets of autoantibodies produced by rheumatoid arthritis patients. Recently, the citrullination of histone proteins by PAD enzyme was reported to influence gene expression levels. These findings greatly increase the interest in the PAD enzymes and their activities. A few procedures to monitor PAD activity in biological samples have been described previously. However, these assays either have low sensitivity or are rather laborious. Here we describe a reliable and reproducible method for the determination of PAD activity in both purified and crude samples. The method is based on the quantification of PAD-dependent citrullination of peptides, immobilized in microtiter plates, using antibodies that are exclusively reactive with the reaction product(s). Our results demonstrate that this antibody-based assay for PAD activity, called ABAP, is very sensitive and can be applied to monitor PAD activity in biological samples.
16879706 Serious psychological distress in U.S. adults with arthritis. 2006 Nov BACKGROUND: Arthritis and mental health disorders are leading causes of disability commonly seen by health care providers. Several studies demonstrate a higher prevalence of anxiety and depression in persons with arthritis versus those without arthritis. OBJECTIVES: Determine the national prevalence of serious psychological distress (SPD) and frequent anxiety or depression (FAD) in adults with arthritis, and in adults with arthritis, identify risk factors associated with SPD. METHODS: Cross-sectional data from the 2002 National Health Interview Survey, an in-person household interview survey, were used to estimate the prevalence of SPD and FAD in adults with (n=6,829) and without (n=20,676) arthritis. In adults with arthritis, the association between SPD and sociodemographic, clinical, and functional factors was evaluated using multivariable logistic regression. RESULTS: The prevalence of SPD and FAD in adults with arthritis is significantly higher than in adults without arthritis (5.6% vs 1.8% and 26.2% vs 10.7%, P<.001, respectively). In adults with arthritis, SPD was significantly associated with younger age, lower socioeconomic status, divorce/separation, recurrent pain, physical inactivity, having functional or social limitations, and having comorbid medical conditions. Adults aged 18 to 44 years were 6.5 times more likely to report SPD than those 65 years or older, and adults with recurrent pain were 3 times more likely to report SPD than those without recurrent pain. CONCLUSIONS: Serious psychological distress and FAD affect persons with arthritis and should be addressed in their treatment. Younger adults with arthritis, and those with recurrent pain or either functional or social limitations, may be at higher risk for SPD.
18500458 Cryptogenic organizing pneumonia (COP), as presentation of rheumatoid arthritis. 2008 Nov We report a 65-year-old caucasian male, who presented cryptogenic organizing pneumonia (COP) as first manifestation of rheumatoid arthritis. The patient started with fever, myalgias and progressive dyspnea in October 2004. The chest X-ray (CXR) and high resolution computed tomographic scan (HRCT) showed diffuse alveolar exudates with air bronchogram in both the lungs. An open lung biopsy was done and the histological image was compatible with COP. Six months later, a diagnosis of RA was made. Treatment with oral methotrexate and etanercept was prescribed with improvement in symptoms, physical examination, and laboratory tests. Even though COP after the joint involvement is found more frequently in RA, in rare cases it could be the first manifestation of this illness.
16468045 Manifestation of rheumatoid arthritis in a patient with hereditary haemochromatosis. 2006 Aug Articular symptoms are frequent manifestations of hereditary haemochromatosis. The clinical signs of the arthropathy of haemochromatosis are not specific and difficult to identify in case of co-incidence of haemochromatosis with Heberden's and Bouchard's osteoarthritis or rheumatoid arthritis (RA). Here the manifestation of RA in a patient is reported who was successfully treated for haemochromatosis. Six months after terminating phlebotomy, the patient presented again suffering from impressive swelling of all MCP joints, showing strong synovitis in ultrasound, and from morning stiffness longer than 1 h. ESR, CRP, IgM rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were markedly elevated. Based on these findings the diagnosis of RA was made. Therefore, the high prevalence of RA and haemochromatosis in the general population underlines the usefulness of a screening for HFE gene mutations in RA patients with an atypical course of the disease as well as in patients with undifferentiated arthritis.
18409573 [A case of rheumatoid arthritis complicated with methotrexate-induced pneumonitis and pneu 2008 Mar A 62-year-old woman with rheumatoid arthritis was given 4 mg/body methotrexate (MTX) every week and 5 mg prednisolone every day. She developed a severe cough starting in the evening after starting taking MTX and after a fever of 38 degrees and dyspnea appeared the patient was hospitalized. On admission, chest CT findings showed diffuse ground glass attenuation. Pathological findings of specimens obtained by transbronchial lung biopsy showed alveolitis with epithelioid cell granuloma. As a section of the specimen did not show cyst staining by Grocott stain, MTX-induced pneumonitis was diagnosed. The same day, methylprednisolone pulse therapy was started and trimethoprim-sulfamethoxazole (TMP-SMX) was given simultaneously, while MTX was discontinued. On hospital day 3, subsequent data showed a high serum level of beta-D glucan and a positive PCR result for Pneumocystis jiroveci in bronchoalveolar lavage fluid (BALF). Additional section of the specimen showed eosinophilic foamy areas on HE staining and cysts measuring 8 microm, consistent with the Pneumocystis jiroveci lesions by Grocott stain. We present a case of rheumatoid arthritis complicated by methotrexate-induced pneumonitis in which pneumocystis pneumonia was demonstrated by clinical and pathological findings.
18576301 Modulation of RANKL and osteoprotegerin expression in synovial tissue from patients with r 2008 Jul 15 OBJECTIVE: To demonstrate the effect of treatment with disease-modifying agents on the expression of osteoprotegerin (OPG) and RANKL in the synovial tissue from rheumatoid arthritis (RA) patients and to correlate these changes with radiologic damage measured on sequential radiographs of the hands and feet. METHODS: Synovial biopsy specimens were obtained at arthroscopy from 25 patients with active RA (16 of whom had a disease duration <12 months) before and at 3-6-month intervals after starting treatment with a disease-modifying agent. Immunohistologic analysis was performed using monoclonal antibodies to detect OPG and RANKL expression, with staining quantitated using computer-assisted image analysis and semiquantitative analysis techniques. Serial radiographs of the hands and feet were analyzed independently by 2 radiologists and a rheumatologist using the van der Heide modification of the Sharp scoring method. RESULTS: Thirteen patients achieved a low disease state as defined by a disease activity score <2.6 while 19 patients achieved an American College of Rheumatology response >20% after disease-modifying antirheumatic drug (DMARD) treatment. Successful DMARD treatment resulted in an increase in OPG expression and a decrease in RANKL expression at the synovial tissue level, which correlated with a reduction in erosion scores measured on annual radiographs of the hands and feet. CONCLUSION: Successful treatment-induced modulation of OPG and RANKL expression at the synovial tissue level, resulting in a reduction in the RANKL:OPG ratio, is likely to have a significant impact on osteoclast formation and joint damage in patients with active RA.
18521704 The role of collagen antibodies in mediating arthritis. 2008 This review examines evidence that rheumatoid arthritis (RA) depends on autoimmunity to articular collagen, and mechanisms whereby autoantibodies to type II collagen contribute to disease development. Three major autoantigenic reactants have been identified in RA; the corresponding autoantibodies are rheumatoid factor (RF), antibodies to citrullinated peptide antigens (ACPA), citrullinated peptides (anti-CCP), and anti-type II collagen (anti-CII). Both RF and ACPA are well-validated and predictive markers of severe erosive RA, but cannot be linked to pathogenesis. By contrast, in various animal species immunized with CII there occurs an erosive inflammatory arthritis resembling that seen in human RA, together with antibodies to CII with an epitope specificity similar to that in RA. We discuss the well-known role of immune complexes in the induction of inflammation within the joint, and present recent data showing, additionally, that antibodies to CII cause direct damage to cartilage in vitro. The close resemblances between human RA and collagen-induced arthritis in animals suggest that autoimmunity, and particularly autoantibodies to CII, are important for both the initiation and perpetuation of RA in a dual manner: as contributors to the inflammation associated with immune complex deposition, and as agents with direct degradative effects on cartilage integrity and its repair.
18495821 Fractalkine in rheumatoid arthritis: a review to date. 2008 Oct Rheumatoid arthritis (RA) is characterized by the expansion of the synovium, with infiltration of pro-inflammatory cells, neovascularization and an abundance of pro-inflammatory cytokines resulting in tissue destruction and bone erosion. Fractalkine (FKN), a recently described chemokine, possesses chemotactic, angiogenic and adhesive functions that associates it with all of these destructive processes. In this review, we describe the research to date, which implicates FKN and its receptor in the pathogenesis of RA and propose that this molecule may represent a future therapeutic target for RA.
17934089 Actin cytoskeleton dynamics linked to synovial fibroblast activation as a novel pathogenic 2007 Nov Rheumatoid arthritis is a chronic inflammatory disorder whose origin of defect has been the subject of extensive research during the past few decades. While a number of immune and non-immune cell types participate in the development of chronic destructive inflammation in the arthritic joint, synovial fibroblasts have emerged as key effector cells capable of modulating both joint destruction and propagation of inflammation. Ample evidence of aberrant changes in the morphology and biochemical behaviour of rheumatoid arthritis synovial fibroblasts have established the tissue evading and "transformed" character of this cell type. We have recently demonstrated that actin cytoskeletal rearrangements determine the pathogenic activation of synovial fibroblasts in modelled TNF-mediated arthritis, a finding correlating with similar gene expression changes which we observed in human rheumatoid arthritis synovial fibroblasts. Here, we show that pharmacological inhibition of actin cytoskeleton dynamics alters potential pathogenic properties of the arthritogenic synovial fibroblast, such as proliferation, migration and resistance to apoptosis, indicating novel opportunities for therapeutic intervention in arthritis. Recent advances in this field of research are reviewed and discussed.
17558711 Relations between serum IgA level and cartilage erosion in 436 cases of rheumatoid arthrit 2007 The objective of this work was to explore the correlation between the cartilage erosion tested with X-ray image and the serum immune globulin level in rheumatoid arthritis (RA). Four hundred and thirty-six patients with active RA in preliminary diagnosis were selected for the study. The cartilage erosion was measured by X ray in both hands as a grade index, and IgG, IgM as well as IgA in serum were determined with immunoturbidimetry. The correlation between the X-ray grading and serum immune globulin outcomes was analyzed by SPSS13.0 statistic package. RESULT: More patients with X-ray grading as cartilage erosion (slight, medium or severe) showed abnormal IgA comparing to those in X-ray grading as normal (p<0.05-0.01) both in preliminary investigation and after 6 months' follow-up. The serum IgA level in RA with X-ray grading as slight, medium or severe cartilage erosion was elevated remarkably comparing with in grading as normal (p<0.05-0.01). The Spearman Analysis showed that the level of serum IgA presents positive correlation with X-ray grading both in preliminary investigation (p=0.003, rIgA=0.143) and after 6 months follow-up (p=0.001, rIgA=0.173). IgG and IgM, however, have no correlation with X-ray image outcomes. The increase of serum IgA shows positive correlation with the grade of cartilage damage in active RA. IgA seems to be involved in the mechanism of joint cartilage erosion in active RA.