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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
17867299 [Transient leukemoid reaction of plasma cells in a patient with rheumatoid arthritis]. 2007 Aug A 69-year-old female with rheumatoid arthritis was admitted to our hospital with facial flushing and cervical lymphadenopathy on Jan, 2006. She had been treated with methotrexate (MTX), sulfasalazine (SSA) and prednisolone. The MTX and SSA were discontinued because of appetite loss just before admission. The patient's white blood cell count was 30100/microl with 32.5% of plasma cells, and 25.7% of plasma cells were observed in the bone marrow. Immunoelectrophoresis revealed polyclonal hypergammaglobulinemia on admission. Flow cytometry analysis revealed that the plasma cells in the bone marrow expressed CD38 and CD19 and did not express CD56. The lymphadenopathy and the increase of plasma cells in the peripheral blood and the bone marrow gradually decreased after the cessation of MTX and SSA.
17090982 The effectiveness of occupational therapy in restoring the functional state of hands in rh 2006 The aim of the study was to evaluate the effectiveness of occupational therapy in rheumatoid arthritis patients with impaired hand function. Standardized Functional Independence Measure was employed in order to evaluate the functional status of the patients and impaired activities. A dynamometer was used for the measurements of muscular strength of hands and a goniometer, for the range of motion of the wrist. Totally, we have examined 120 rheumatoid arthritis patients. They were divided into two groups: 60 patients in each. Occupational therapy was applied only to the patients of the first group. The mean age of Group 1 patients was 53.4+/-1.8 years, the mean age of Group 2 patients was 52.0+/-1.9 years. The mean duration of the disease was 11.5+/-2.6 years and 12.1+/-2.4 years, respectively. The effectiveness of therapy was considered ineffective if, after the completion of the course of occupational therapy, no increase in Functional Independence Measure score for patients with rheumatoid arthritis was observed. When the score increased from 1 to 3, we considered this as moderate effectiveness; when the score increased to 4-6, we evaluated the effectiveness of occupational therapy as good, and when the score of 7 was attained, effectiveness of occupational therapy was considered as very good. In Group 1, the moderate effectiveness of occupational therapy was determined in 31.7% of patients; good effectiveness, in 61.7%; and very good effectiveness, in 3.3% of rheumatoid arthritis patients. In Group 2, the moderate effectiveness of treatment was determined in 48.3% of patients and good effectiveness, in 5% of rheumatoid arthritis patients. CONCLUSIONS. Hand function (the strength of fingers and hands, the range of motion of the wrist) significantly improved in patients with rheumatoid arthritis after completion of a course of occupational therapy (p<0.05). The improvement of hand functions in patients with rheumatoid arthritis led to increased ability to take food and drink, to wash themselves, to put the clothes on the upper and lower parts of the body and take them off, to use the toilet, a bathtub or a shower, to walk, to manage a wheelchair, and to do personal hygiene (p<0.05).
18388516 New approaches of B-cell-directed therapy: beyond rituximab. 2008 May PURPOSE OF REVIEW: This study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity. RECENT FINDINGS: Beyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported. SUMMARY: The value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.
18377031 Multipixel system for gigahertz frequency-domain optical imaging of finger joints. 2008 Mar Frequency-domain optical imaging systems have shown great promise for characterizing blood oxygenation, hemodynamics, and other physiological parameters in human and animal tissues. However, most of the frequency domain systems presented so far operate with source modulation frequencies below 150 MHz. At these low frequencies, their ability to provide accurate data for small tissue geometries such as encountered in imaging of finger joints or rodents is limited. Here, we present a new system that can provide data up to 1 GHz using an intensity modulated charged coupled device camera. After data processing, the images show the two-dimensional distribution of amplitude and phase of the light modulation on the finger surface. The system performance was investigated and test measurements on optical tissue phantoms were taken to investigate whether higher frequencies yield better signal-to-noise ratios (SNRs). It could be shown that local changes in optical tissue properties, as they appear in the initial stages of rheumatoid arthritis in a finger joint, are detectable by simple image evaluation, with the range of modulation frequency around 500 MHz proving to yield the highest SNR.
18173925 Delayed neutrophil apoptosis in very early rheumatoid arthritis patients is abrogated by m 2007 Nov OBJECTIVES: To analyse the activation state and apoptosis of circulating neutrophils in untreated very early rheumatoid arthritis (VERA) and after exposure to low dose corticosteroids and methotrexate (MTX). METHODS: Neutrophils were isolated from the peripheral blood of VERA patients at 3 different times: before any treatment was started, 2 weeks after starting a low dose of prednisone (5-10 mg) and 4 months after reaching more than 20mg/week of MTX. The expression of different activation markers (CD11b, CD64, CD86 and CD69) in freshly isolated neutrophils was analysed by flow cytometry. Apoptosis was measured by the loss of DNA content, which was analysed by flow cytometry using propidium iodide. RESULTS: Compared to neutrophils from healthy controls, we have found a delayed neutrophil apoptosis within 6 h and 22 h of cultured polymorphonuclear leukocytes (PMN) derived from VERA patients without any treatment or treated with corticosteroids. The delay of PMN apoptosis was restored to control levels after treatment with MTX. CONCLUSION: The treatment of VERA patients with corticosteroids did not affect the delay of neutrophil apoptosis. However, delayed apoptosis was restored to control levels after treatment with low dose MTX, which highlights the importance of early RA treatment with MTX.
17634188 Tai chi for rheumatoid arthritis: systematic review. 2007 Nov The objective of this systematic review is to evaluate data from controlled clinical trials testing the effectiveness of tai chi for treating rheumatoid arthritis (RA). Systematic searches were conducted on Medline, Pubmed, AMED, British Nursing Index, CINAHL, EMBASE, PsycInfo, The Cochrane Library 2007, Issue 1, the UK National Research Register and ClinicalTrials.gov, Korean medical databases, Qigong and Energy Medicine Database and Chinese databases up to January 2007. Hand-searches included conference proceedings and our own files. There were no restrictions regarding the language of publication. All controlled trials of tai chi for patients with RA were considered for inclusion. Methodological quality was assessed using the Jadad score. The searches identified 45 potentially relevant studies. Two randomized clinical trials (RCTs) and three non-randomized controlled clinical trials (CCTs) met all inclusion criteria. The included RCTs reported some positive findings for tai chi on disability index, quality of life, depression and mood for RA patients. Two RCTs assessed pain outcomes and did not demonstrate effectiveness on pain reduction compared with education plus stretching exercise and usual activity control. The extent of heterogeneity in these RCTs prevented a meaningful meta-analysis. Currently there are few trials testing the effectiveness of tai chi in the management of RA. The studies that are available are of low methodological quality. Collectively this evidence is not convincing enough to suggest that tai chi is an effective treatment for RA. The value of tai chi for this indication therefore remains unproven.
16333645 [Health economic research in rheumatic diseases]. 2006 Jan Thorough health economic research of budget-relevant diseases should be one of the major tasks in the German health care system. Up to now cost studies were only performed for special research questions and/or with very limited focuses, e.g. the patients' view. Hence, federal programmes, like competence networks for certain diseases, which were introduced by the German Ministry for Research and Education in the late 1990s, should give a broader focus on health services research. With such an approach health politicians may obtain a deeper insight into areas of the health care sector which are likely to be more efficient after reorganisation. The process of a structured analysis of certain diseases will be demonstrated using the example of rheumatoid arthritis (RA). To this end, the results of a research programme sponsored within the Competence Network for Musculoskeletal Diseases will be presented. Direct costs, indirect costs as well as values for health-related quality of life of German RA patients in routine care by generalists and specialists will be discussed.
16870104 Effect of Avemar--a fermented wheat germ extract--on rheumatoid arthritis. Preliminary dat 2006 May OBJECTIVE: To investigate the effect of the fermented wheat germ extract (Avemar)in patients with severe rheumatoid arthritis (RA). METHODS: Fifteen female RA (Steinbrocker II-III) patients, who had unsuccessfully tried two different DMARD treatments, were enrolled in an open-label, 1-year long, pilot clinical study. DMARD and steroid therapies were recorded and continued. All patients received Avemar as additional therapy. For measurement of efficacy the Ritchie Index, the Health Assessment Questionnaire (HAQ) and the assessment of morning stiffness were applied. Patients were evaluated at baseline, 6 and 12 months. For statistical analyses the Wilcoxon test was used. RESULTS: At both 6 and 12 months, Ritchie index, HAQ and morning stiffness showed significant improvements compared with the baseline values. Dosages of steroids could be reduced in about half of the patients. No side effects of Avemar were observed. CONCLUSION: Supplementation of standard therapies with a continuous administration of Avemar is beneficial for RA patients.
18022616 Mechanism of action of the disease-modifying anti-arthritic thiol agents D-penicillamine a 2008 Feb 2 While new anti-cytokine disease-modifying anti-arthritic drugs for rheumatoid arthritis have been designed via mechanistic approaches, the mechanism of action of a number of more established disease-modifying anti-arthritic drugs has not been elucidated. In the case of d-penicillamine and sodium aurothiomalate, the key structural feature appears to be a free thiol group. However, the role thiol groups play in the therapeutic efficacy of these drugs has not been defined. A number of lines of evidence have demonstrated increased generation of reactive aldehydes and the associated depletion of free thiol pools in rheumatoid arthritis. These observations have led to the suggestion that reactive aldehydes may be the ultimate mediators of cell destruction in rheumatoid arthritis joints. Our data clearly demonstrate that thiol-containing disease-modifying anti-arthritic agents both directly sequester reactive aldehydes and augment intracellular thiol pools, which also can buffer increased aldehyde load and oxidative stress. These data are consistent with clinical data that penicillamine lowers synovial aldehyde levels and augments plasma thiols. We suggest that these actions are the pivotal mechanism of action of thiol-containing disease-modifying anti-arthritic drugs. Understanding the mechanism of action of these drugs provides the opportunity for the design of more potent and safer thiol drug candidates.
17312183 A critical role for allograft inflammatory factor-1 in the pathogenesis of rheumatoid arth 2007 Mar 1 Rheumatoid arthritis (RA) is characterized by massive synovial proliferation, angiogenesis, subintimal infiltration of inflammatory cells and the production of cytokines such as TNF-alpha and IL-6. Allograft inflammatory factor-1 (AIF-1) has been identified in chronic rejection of rat cardiac allografts as well as tissue inflammation in various autoimmune diseases. AIF-1 is thought to play an important role in chronic immune inflammatory processes, especially those involving macrophages. In the current work, we examined the expression of AIF-1 in synovial tissues and measured AIF-1 in synovial fluid (SF) derived from patients with either RA or osteoarthritis (OA). We also examined the proliferation of synovial cells and induction of IL-6 following AIF-1 stimulation. Immunohistochemical staining showed that AIF-1 was strongly expressed in infiltrating mononuclear cells and synovial fibroblasts in RA compared with OA. Western blot analysis and semiquantitative RT-PCR analysis demonstrated that synovial expression of AIF-1 in RA was significantly greater than the expression in OA. AIF-1 induced the proliferation of cultured synovial cells in a dose-dependent manner and increased the IL-6 production of synovial fibroblasts and PBMC. The levels of AIF-1 protein were higher in synovial fluid from patients with RA compared with patients with OA (p < 0.05). Furthermore, the concentration of AIF-1 significantly correlated with the IL-6 concentration (r = 0.618, p < 0.01). These findings suggest that AIF-1 is closely associated with the pathogenesis of RA and is a novel member of the cytokine network involved in the immunological processes underlying RA.
16891219 The expression of collagenase 3 (MMP-13) mRNA in the synovial tissue is associated with hi 2006 Jun The histopathologic analysis of the synovial tissue is important to distinguish rheumatoid arthritis (RA) from other forms of synovitis and to provide information about prognosis and therapeutic strategies at early stages of the disease. In this context, the present study was performed to investigate the correlation between immunohistopathological and morphological features of synovitis and the expression of collagenase 3 (MMP-13) known to contribute significantly to cartilage degradation in RA. In the histopathologic scoring system used in this study, type I synovitis is characterized by B lymphocyte infiltration and an intact lining, and is only mild destructive to cartilage and bone. Type II shows marked diffuse infiltrations of macrophages and T lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%) were positive for the expression of collagenase 3 mRNA in the synovial tissue. Among these patients, 19 showed a histopathologic type II synovitis and only 2 patients had undifferentiated synovitis. In contrast, synovial tissue samples from patients without collagenase 3 mRNA expression were characterized in 6 cases by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis. The analysis of the clinical data revealed that RA patients with a histopathologic type II synovitis and synovial tissue collagenase 3 mRNA expression had elevated levels of systemic markers of inflammation and received stronger therapies. The data suggest, that collagenase 3 expression and the histopathologic type II synovitis are associated with a severe and destructive course of RA.
17642230 [Clinical development and future perspective of biological agents]. 2007 Jul Biological agents targeting against a series of pro-inflammatory cytokines have provided an enormous impact on the therapeutic management on inflammatory disorders such as rheumatoid arthritis. Clinical development of biological agents in Japan, particularly, TNF inhibitors, has been reviewed in this paper, and future perspective is discussed.
18381797 Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families. 2008 May OBJECTIVE: To investigate whether frequency of rheumatoid arthritis (RA) and/or other autoimmune (AI) disorders was increased in RA French Caucasian families among the first- (FDR) and second-degree relatives (SDR), and to test whether the presence of AI disease family history identified a specific RA subset. METHODS: We conducted telephone interviews to obtain histories of AI diseases among the FDR and SDR of 368 RA probands, belonging either to trio or affected sib-pair (ASP) families. All the AI diagnoses were confirmed by the physician of the affected relative. RESULTS: Probands of the ASP families were characterized by older age at RA onset, longer disease duration, and larger family size versus trio families. In the trio families, the prevalence of AI diseases was 6.05% (4.76%-7.57%) in FDR and 2.40% (1.85%-3.06%) in SDR. In ASP families, the prevalence of AI diseases was, respectively, 10.24% (8.68%-11.97%) and 1.79% (1.41%-2.25%). The most frequent AI diseases among relatives were RA, thyroid AI diseases, and vitiligo. In trio families, a proband with a mean age of RA onset < 30 years was associated with AI disease prevalence in the relatives, and male gender was associated with prevalence of RA among the FDR. CONCLUSION: The prevalence of AI diseases is increased, particularly among FDR, in French RA families, and some characteristics of the RA proband seem to be associated with prevalence of AI diseases in families.
17694264 Imatinib mesylate both prevents and treats the arthritis induced by type II collagen antib 2007 Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint destruction. Imatinib mesylate (imatinib) is an inhibitor that specifically targets a set of protein tyrosine kinase, such as abl, c-kit, and platelet-derived growth factor receptor (PDGFR) and it is widely used to treat chronic myeloid leukemia (CML). The purpose of the present study is to determine whether imatinib can provide benefit in the arthritis induced by anti-collagen type II antibody (CAIA) in mice, a model that provides an opportunity to study the effector inflammatory phase of arthritis without involving the priming phase of the immune responses. Mice treated with intraperitoneal administration of imatinib (1 or 10 mg/kg) prior to the development of CAIA displayed significant reductions in the severity of CAIA as assessed by arthritis score, histology, and synovial PDGF and vascular endothelial growth factor expression. In addition, treatment of the mice that had developed CAIA with intraperitoneal administration of imatinib (1 or 10 mg/kg) inhibited the progression of arthritis as assessed by those parameters. These results suggest that imatinib prevents and treats CAIA. Imatinib may thus have both a preventive and therapeutic potential for the joint inflammation at the effector stage of RA.
17139662 Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A 2006 Dec 15 OBJECTIVE: Although early initiation of disease-modifying antirheumatic drugs (DMARDs) is effective in controlling short-term joint damage in individuals with rheumatoid arthritis (RA), the long-term benefit in disease progression is still controversial. We examined the long-term benefit of early DMARD initiation on radiographic progression in early RA. METHODS: We identified published and unpublished clinical trials and observational studies from 1966 to September 2004 examining the association between delay to treatment initiation and progressive radiographic joint damage. We included studies of persons with RA disease duration <2 years and DMARD therapy of similar efficacy during followup. The differences in annual rates of radiographic progression between early and delayed therapy were pooled as standardized mean differences (SMDs). RESULTS: A total of 12 studies met the inclusion criteria. The pooled estimate of effects from these studies demonstrated a significant reduction of radiographic progression in patients treated early (-0.19 SMD, 95% confidence interval [95% CI] -0.34, -0.04), which corresponded to a -33% reduction (95% CI -50, -16) in long-term progression rates compared with patients treated later. Patients with more aggressive disease seemed to benefit most from early DMARD initiation (P = 0.04). CONCLUSION: These results support the existence of a critical period to initiate antirheumatic therapy, a therapeutic window of opportunity early in the course of RA associated with sustained benefit in radiographic progression for up to 5 years. Prompt initiation of antirheumatic therapy in persons with RA may alter the long-term course of the disease.
18716729 Prevalence of subjective voice impairment in rheumatoid arthritis. 2008 Nov Rheumatoid arthritis (RA) might lead to voice impairment through several mechanisms but its prevalence has been little investigated. RA patients attending a rheumatology outpatient clinic had joint assessments and completed the Voice Handicap Index-10 (VHI-10). A comparator group consisted of patients attending the department with other diseases. Seventy-three patients with RA and 73 comparators were recruited. Four patients with RA (5%) and one comparator (1%) had significantly abnormal VHI-10 scores. RA patients with a Disease Activity Score 28 >3.2, indicating more active disease, had significantly higher VHI-10 scores. A low prevalence of self-reported voice handicap occurs in RA and associates with more active disease.
18438843 The shared epitope hypothesis in rheumatoid arthritis: evaluation of alternative classific 2008 May OBJECTIVE: Many classification systems for the HLA-DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK. METHODS: HLA-DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK. Logistic regression analyses were performed to investigate the different classification systems. RESULTS: We confirmed the association between the susceptibility alleles S2 and S3P, as proposed by Tezenas du Montcel, and the presence of RA in UK Caucasians. A significant hierarchy of risk was observed within the S3P allele group. There was no evidence of a significant association between DRB1*1001 and RA. Our data did not support the hypothesis that an isoleucine at position 67 conferred protection against RA, other than in contrast to the susceptibility alleles. However, the presence of an aspartic acid at amino acid 70 did appear to confer some degree of protection. CONCLUSION: We were unable to fully substantiate any of the 3 recent revisions of the shared epitope hypothesis in this large cohort of Caucasian RA patients and control subjects in the UK. This reinforces the importance of evaluating disease susceptibility alleles in different Caucasian populations as well as in other ethnic groups. In particular, it will be important to clarify the precise DRB1 association in a given population before DRB1 genotyping is incorporated into clinical diagnostic or treatment algorithms.
18306979 Tacrolimus-induced lung injury in a rheumatoid arthritis patient with interstitial pneumon 2008 A 74-year-old woman was experiencing rheumatoid arthritis complicated with interstitial pneumonitis (IP), and tacrolimus treatment was started. She presented with dyspnea. Chest X-ray and computed tomography (CT) showed ground-glass opacity and IP. Although tacrolimus was stopped, she died of respiratory failure. At autopsy, both the upper and lower lung fields showed usual IP and the organizing stage of diffuse alveolar damage. The former is common, but the latter is uncommon, suggesting tacrolimus may cause severe alveolar damage.
17221249 [The treatment of periprosthetic infections]. 2007 Feb Periprosthetic infections are severe complications following total joint arthroplasty. The infection rate is estimated to be 0.5-2%. Systemic diseases such as rheumatoid arthritis and previous surgery are considered risk factors for infection. The infection rate in the present patient cohort was low (0.72%). The recurrence rate (23.4%) is due to patients with rheumatoid arthritis and septic total knee arthroplasties. Successful treatment is dependent on various factors, one of which involves accurate preoperative bacterial diagnostics. Joint fluid aspiration is the appropriate procedure. Open biopsy or arthroscopically guided biopsy can be performed in cases of unclear diagnostic results. Early infection can be treated with thorough joint debridement without exchanging fixed implant components; "low-grade" or late infections require revision with implant removal in a one or two stage septic revision according to clearly determined algorithms. Antibiotic therapy is mandatory, and a combination with rifampicin is a very useful basis.
18375972 Beliefs about medicines in patients with rheumatoid arthritis and systemic lupus erythemat 2008 May OBJECTIVE: To assess whether patients with RA and SLE who are of South Asian origin have different beliefs about medicines in general, and about DMARDs in particular, compared with patients of White British/Irish origin. METHODS: One hundred patients of South Asian origin (50 RA; 50 SLE) and 100 patients of White British/Irish origin (50 RA; 50 SLE) were recruited. Demographic and disease-related details and responses to the Beliefs about Medicines Questionnaire (BMQ), the SF-36 and the HAQ were collected. RESULTS: Patients of South Asian origin had significantly higher General Overuse (GO), General Harm (GH) and Specific Concern (SC) scores compared with patients of White British/Irish origin. Forward stepwise multivariable regression analysis showed that ethnic origin was an independent predictor of the GO, GH and SC scores with patients of South Asian origin having higher scores in these three scales of the BMQ. CONCLUSION: RA and SLE patients of South Asian origin have very high levels of concern about DMARDs and are generally worried about prescribed medicines. This may have an impact on adherence in this group of patients and further work is needed to understand the reasons underlying these beliefs.