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ID PMID Title PublicationDate abstract
17105483 Synthesis of overlapping fibrin citrullinated peptides and their use for diagnosing rheuma 2006 Oct With the aim of developing a new enzyme-linked immunosorbent assay test to detect autoantibodies in the sera of rheumatoid arthritis patients with a high sensitivity and specificity using synthetic citrullinated peptides of fibrin (which is abundant in rheumatoid synovium) as antigenic substract, peptides belonging to alpha- and beta-fibrin chains were selected by computer-aided prediction of antigenicity and epitope mapping and synthesized in solid phase. We analysed by enzyme-linked immunosorbent assay 133 sera from patients with well-characterized rheumatic diseases, including 67 patients with rheumatoid arthritis. The results of the immunoassays reported highlight the usefulness of fibrin-related peptides in rheumatoid arthritis diagnosis and, especially, the ability and specificity of the [Cit(621,627,630)]alpha-fibrin(617-631) (alpha fib617) peptide sequence to recognize the autoantibodies that are present in rheumatoid arthritis patients.
16923515 EBV-associated synovial lymphoma in a chronically inflamed joint in rheumatoid arthritis r 2006 Aug A patient with longstanding rheumatoid arthritis (RA) developed swelling in a chronically inflamed knee joint while receiving prolonged methotrexate treatment. Magnetic resonance imaging and positron-emission tomography showed soft tissue swelling with intense tracer uptake. Biopsy confirmed high-grade B-cell lymphoma. He developed complete remission with rituximab plus CEOP. The role of chronic inflammation and methotrexate in the pathogenesis of lymphoma in RA was discussed.
17951674 Gene transfer to synovial fibroblast: methods and evaluation in the SCID mouse model. 2007 The use of gene transfer techniques has become of utmost importance both for the analysis of molecular pathways of rheumatic joint destruction and for the evaluation of novel therapeutic concepts to treat rheumatic diseases. However, gene transfer into synovial fibroblasts faces several challenges, which result mainly from the lack of specific surface markers and the low-proliferation rate of these cells. This chapter describes both nonviral and viral strategies of transferring gene constructs into synovial fibroblasts. It focuses on the use of lipofection for the gene transfer of siRNA to synovial fibroblasts and the use of AMAXA-nucleofection for the nonviral transfer of gene expression constructs. In addition, retro- and lentiviral strategies of gene transfer are introduced. Finally, the SCID mouse in vivo model of rheumatoid joint destruction is described as a means of evaluating the effects of gene transfer on the invasiveness of synovial fibroblasts.
18396335 Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. 2008 Jun 15 Experimental and clinical evidence for T cell involvement in the pathology of rheumatoid arthritis (RA) is compelling, and points to a local dysregulation of T cell function in the inflamed joint. Nitric oxide (NO) has been shown to regulate T cell function under physiological conditions, but overproduction of NO may contribute to lymphocyte dysfunction characteristic of RA. Several investigations in patients with RA have documented evidence of increased NO synthesis, but these studies have focused largely on macrophage-derived NO and its impact on innate immune and inflammatory responses. In this study, we set out to explore the contribution that T cells make to NO production. We find that T cells from RA patients produce >2.5 times more NO than healthy donor T cells (p<0.001). Although NO is an important physiological mediator of mitochondrial biogenesis, mitochondrial mass is similar in RA and control T cells. In contrast, increased NO production is associated with increased cytoplasmic Ca(2+) concentrations in RA T cells (p<0.001). In vitro treatment of human peripheral blood lymphocytes, or Jurkat cells with TNF increases NO production (p=0.006 and p=0.001, respectively), whilst infliximab treatment in RA patients decreases T cell derived NO production within 6 weeks of the first infusion (p=0.005). Together, these data indicate that TNF induced NO production in T lymphocytes may contribute to perturbations of immune homeostasis in RA.
18270858 B-cell depletion and repopulation in autoimmune diseases. 2008 Feb Although T-lymphocytes have long been regarded as the prime effector of autoimmune diseases, numerous studies have since highlighted a key role for B-lymphocytes. For example, disturbances in the distribution of circulating B-cell subsets were reported in primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Consequently, this was the rationale to treat such patients for B-cell depletion with anti-CD20 monoclonal antibody (rituximab). The aim of this review is to describe and analyze the B-cell subset distribution at baseline and after rituximab therapy in patients with SLE, rheumatoid arthritis, and pSS. Finally, we will compare factors that may interfere with anti-CD20-mediated B-cell depletion in these autoimmune diseases.
16362366 The effect of circulating nitric oxide level on axial bone mineral density in postmenopaus 2006 Jul The aim is to investigate the differences in the circulating nitric oxide (NO) levels of rheumatoid arthritis (RA) patients, healthy controls and osteoporotic (OP) patients. We also examined whether the circulating NO levels may be correlated with bone mineral density (BMD) in RA patients. Forty-five patients with RA, 30 healthy women and 30 osteoporotic patients were recruited from the outpatient clinic. All the subjects were female and postmenopausal. Serum NO levels were measured (Nitrite/Nitrate, calorimetric method 1746081, Roche diagnostics, Mannheim, Germany) and BMD was measured at the spine and hip using dual energy X-Ray absorbtiometry (DEXA, Norland XR-46). Height and weight were measured and body mass index was calculated. Circulating NO levels were significantly higher in RA patients than other groups. Moreover, the RA group showed significantly higher BMD at lumbar spine and femoral neck regions compared to osteoporotic patients. However, the RA group showed significantly lower BMD at all sites than the controls. There was no correlation between circulating NO levels and BMD in all groups. We suggest that, unlike postmenopausal osteoporosis, inflammation induced osteoporosis is associated with RA is characterised by relatively preserved bone mass at the axial bone regions, and circulating NO levels as a parameter or determinant of inflammation are not correlated with axial BMD in RA patients.
17289546 What is after cytokine-blocking therapy, a novel therapeutic target--synovial Epstein-Barr 2007 Jan There has been significant progress in cytokine-blocking therapy for treatment of rheumatoid arthritis (RA) However, inhibition of cytokines involved in immune defense raises severe side effects. The cost of cytokine-blocking treatment is another major issue. Why are levels of inflammatory cytokines increased in RA patients? We have a large amount of circumstantial and direct evidence for the presence of Epstein-Barr virus (EBV) in RA synovial cells. Here, we provide an overview of the implications for novel approaches to therapy for RA patients, based on the most recent available evidences of anti-viral agents.
16783865 Most rheumatologists are conservative in active rheumatoid arthritis despite methotrexate 2006 Jul OBJECTIVE: To evaluate the proportion of patients with rheumatoid arthritis (RA) visiting office-based rheumatologists for persistently active RA despite past or current methotrexate (MTX) treatment, and to describe the management of these patients in France in 2003. METHODS: All French rheumatologists were invited to participate in a cross-sectional postal survey. During a predetermined week, they were to include the first 2 patients seen for RA with a history of past or current MTX treatment. Adequacy of current treatment was assessed based on the 28-joint Disease Activity Score 28 (DAS28) and on current MTX and corticosteroid regimens. RESULTS: Of the 1800 French rheumatologists, 492 returned 838 assessable patient questionnaires. Mean patient age was 58 years and mean time since RA diagnosis was 10 years; 77% of patients were currently taking MTX, and 51% a corticosteroid. High dosages were noted for MTX (> 15 mg/week) in 20% of patients and for corticosteroid therapy (> 10 mg/day) in 5%. Nevertheless, 41% of patients had active RA (DAS28 score 3.2 to 5.1) and 7% had very active RA (DAS28 score > 5.1). The treatment was left unchanged in 78% of patients, and biological therapy was contemplated in only 16% of patients. CONCLUSION: Although half of MTX-treated patients with RA visiting office-based rheumatologists had active or very active disease, a change in treatment was rarely considered.
19051702 Assessment of atherosclerosis by carotid intimomedial thickness in patients with rheumatoi 2008 Aug OBJECTIVES: To determine the prevalence of subclinical (asymptomatic) atherosclerosis in patients with rheumatoid arthritis (RA) and to study the variables affecting such an occurrence. METHODS: Case control study which included 100 patients with RA having disease duration more than 5 years and 100 healthy age and sex matched controls. Cases and controls symptomatic for atherosclerosis or having traditional risk factors for atherosclerosis were excluded. Both cases and controls were subjected to carotid ultrasound examination in addition to detailed history and physical examination. RESULTS: The study population (both cases and controls) included 94 females and 6 males. The mean age of cases and controls was similar (44.06 +/- 11.32 years and 44.1 +/- 11.52 years). The mean disease duration was 155.04 +/- 48.8 months. The mean carotid intimo-medial thickness (CIMT) of the RA patients (0.519 +/- 0.18 mm) was significantly greater than the controls (0.387 +/- 0.085). Age and disease duration were the only factors found to significantly affect CCIMT. RA patients had higher prevalence of carotid plaques (21%) compared to controls (1%). Erosions on hand radiographs were the only significant predictor of plaques in patients with RA. CONCLUSION: Patients with RA exhibit premature atherosclerosis by way of increased CIMT and carotid plaques when compared to age and sex matched controls.
17404474 [New therapeutic strategy of rheumatoid arthritis to reach the goal of suppression of join 2007 Apr Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis and bone damages, which consist of joint destruction. The pathogenesis of RA is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now defined in more detail. Previous therapy, slow acting disease-modifying antirheumatic drugs (DMARDs) as with low-dose methotrexate (MTX) were accepted for RA and lead to a significant improvement of disease symptoms, however were unable to stop joint destruction. Recently therapeutic strategies using biologics including infliximab and etaner-cept are effective for treating RA disease activity and reduce joint destruction. Moreover it has been shown that disability and joint destruction occur early in the course of RA and progress rapidly. These findings support the hypothesis "window of opportunity for therapeutic intervention in RA" , and the aggressive therapy early in the course of RA is expected to result in the induction of remission or, perhaps most important, a chance of cure.
18525360 Do antitumor necrosis factor agents increase the risk of postoperative orthopedic infectio 2008 Jul PURPOSE OF REVIEW: Patients with rheumatoid arthritis and other inflammatory arthritides treated with tumor necrosis factor inhibitors frequently undergo orthopedic procedures. These patients may be at risk for serious postoperative infections as antitumor necrosis factor agents may be associated with impaired immunity against usual and opportunistic pathogens. RECENT FINDINGS: Information regarding the influence of tumor necrosis factor inhibitors on the risk for postoperative orthopedic complications is limited, contradictory and solely based on retrospective studies. Basic science derived data seem to only add to the confusion. SUMMARY: The practitioner is at a loss whenever a decision regarding the perioperative handling of antitumor necrosis factor agents has to be made. An attempt to combine, reconcile, and expand the knowledge available in the current literature will be made.
17343801 Targeting stromal cells in chronic inflammation. 2007 Feb Why chronic inflammatory reactions persist in specific sites, such as rheumatoid arthritis in the joints, remains a mystery. Current models of inflammation have concentrated upon the responses of lymphocytes such as B and T cells to specific antigens, and have attempted, often unsuccessfully, to address the causative agent. However recent studies have shown that stromal cells such as macrophages, endothelial cells, and fibroblasts play important roles in the switch that turns a spontaneously resolving acute inflammatory response within a tissue into chronic and persistent disease. Therapeutic manipulation of the stromal microenvironment has been particularly effective in treating cancer and is likely to provide novel therapies to achieve improved control of chronic inflammatory disease.
18627570 Investigation of CD69 as a new candidate gene for rheumatoid arthritis. 2008 Sep The aim of this study was to investigate the CD69 gene as a new functional candidate gene for rheumatoid arthritis (RA) genetic predisposition. A case-control association study including 933 RA patients and 800 healthy individuals was conducted. Five haplotype-tagging single nucleotide polymorphisms (SNPs) (rs929615, rs3176806, rs4763299, rs11052877, and rs3176789) covering the CD69 gene coding, 5' and 3' untranslated regions were selected as CD69 genetic markers and genotyped using a Taqman 5' allelic discrimination assay. No statistically significant differences were observed in the single marker association study with regard to either genotypic or allelic frequencies when considering the rs929615, rs3176806, rs4763299, rs11052877, and rs3176789 CD69 SNPs independently. According to these findings, no statistically significant skewing was observed between the RA patients and the controls in the distribution of CD69 haplotypes. In summary, our results do not support a major role for the CD69 gene polymorphisms in RA genetic predisposition in our population.
18484253 The foot: still the most important reason for walking incapacity in rheumatoid arthritis: 2008 Apr BACKGROUND AND PURPOSE: Our knowledge of frequency of foot involvement in rheumatoid arthritis (RA) is still often based on a study from Finland in 1956. Great changes in the treatment of RA may have led to a different situation. We investigated the distribution of joint involvement in RA patients today, with special attention given to the feet and subjective walking ability. METHODS: 1,000 RA patients answered a questionnaire concerning joints affected, joint surgery, foot problems, and subjectively experienced reasons for walking incapacity. RESULTS: In 45% of the patients, the forefoot was involved at the start of the disease. In 17%, the hindfoot/ankle was involved at the start. Only hand symptoms were commoner. 80% of patients reported current foot problems, 86% in the forefoot and 52% in the hindfoot/ankle. Difficulty in walking due to the feet was reported by 71%. For 41% of patients, the foot was the most important part of the lower extremity causing reduced walking capacity, and for 32% it was the only part. INTERPRETATION: After the hand, the foot was the most frequently symptomatic joint complex at the start of the disease, but also during active medical treatment. The foot caused walking disability in three-quarters of the cases and-4 times as often as the knee or the hip-it was the only joint to subjectively impair gait.
18368795 [Risk factors of cardiovascular diseases in patients with rheumatoid arthritis]. 2008 Rheumatoid arthritis (RA) is associated with an increased cardiovascular risk, which cannot be explained by conventional risk factors. Arterial rigidity is an independent cardiovascular risk factor in RA patients. The aim of the investigation was to study arterial rigidity in RA patients in the absence of classic risk factors. Arterial rigidity was measured with the arteriographer Tensioclinic (Tensiomed, Hungary) in 17 patients with the diagnosis of RA made according to American College of Rheumatologists diagnostic criteria, and 22 healthy persons without cardiovascular risk factors. Systolic, diastolic, and mean arterial pressure, heart rate, brachial and aortal augmentation index (AI), the time of pulse wave (PW) return from the aorta, PW velocity in the aorta (PWVA), and the square of the systolic and diastolic PW components were measured. Compared with the controls, arterial rigidity was increased in the RA patients. AI in the aorta was 25.09 +/- 12.75% vs. 17.63 +/- 10.01% in the controls (p = 0.04); AI in the brachial artery was - 17.62 +/- 30.09% and -35.22 +/- 23.6%, respectively. PWVA was much higher in the RA patients vs. the controls (8.98 +/- 1.89 m/sec and 720 +/- 1.84 m/sec, respectively). Thus, in the absence of conventional cardiovascular risk factors RA may be considered an independent risk factor of an increased arterial rigidity.
18972729 [Observation on therapeutic effect of the spreading moxibustion on rheumatoid arthritis]. 2008 Oct OBJECTIVE: To search for an effective therapy for rheumatoid arthritis (RA). METHODS: Fifty-six cases of RA were randomly divided into a spreading moxibustion group of 31 cases and an acupuncture group of 25 cases. The spreading moxibustion group were treated by moxibustion on the Governor Vessel, from Dazhui (GV 14) to Yaoshu (GV 2), and bilateral corresponding Jiaji (EX-B 2), with drug powder composed of Qianghuo (Notoperygium root), Duhuo (Pubescent angelica root), Niuxi (Achyranthes root), etc. and fresh mashed ginger were spread at the points; and the acupuncture group were treated by simple acupuncture at Dazhu (GV 14) and Shenzhu (GV 12), etc. They were treated for 50 days. RESULTS: The effective rate was 100.0% in the spreading moxibustion group and 84.0% in the acupuncture group with a significant difference between the two groups (P < 0.05). CONCLUSION: Spreading moxibustion has an significant therapeutic effect on rheumatoid arthritis.
18174232 Personal and economic burden of late-stage rheumatoid arthritis among patients treated wit 2008 Feb OBJECTIVES: This study evaluated the patients' perspective of burden of disease among 505 patients with severe, long-standing rheumatoid arthritis receiving adalimumab. METHODS: Health-related quality-of-life and resource use data were collected during a 144-week open-label study. RESULTS: Adalimumab maintained pain control and reduced the duration of morning stiffness. Work impairment decreased and work productivity was maintained over the duration of the study. Costs were estimated at approximately 2100 euros over the course of the study, and personal help and transportation costs comprised a large percentage of total costs. CONCLUSIONS: These results suggest that adalimumab could improve many aspects of a patient's burden of disease.
18926166 Role of inflammation in atherosclerosis associated with rheumatoid arthritis. 2008 Oct Rheumatoid arthritis (RA) is associated with excess morbidity and mortality from myocardial infarction and allied disorders. A large body of evidence supports the involvement of common proinflammatory cytokines in the development and progression of both RA and atherosclerosis. The destructive proinflammatory cascade and effector mechanisms implicated in RA resemble the chronic inflammatory processes that drive the development of atherosclerosis in general. Proinflammatory cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha produced within locally affected joints in RA may promote both traditional (e.g., dyslipidemia, insulin resistance) and nontraditional (e.g., oxidative stress) systemic cardiovascular risk factors. Expression of proinflammatory cytokines and inflammatory mediators influences all stages of atherosclerosis development, from early atheroma formation to thrombus development responsible for events such as myocardial infarction. Appreciation of the inflammatory process shared by RA and atherosclerosis should heighten the recognition of this morbid association and lead to better recognition and management of cardiovascular risk in patients with rheumatologic diseases.
17346422 BAFF and rheumatic autoimmune disorders: implications for disease management and therapy. 2007 Jan Interest in B-cells has been revived due to the description of new functions. Supporting a role for B-cells in the genesis of autoimmune diseases is the fact that the B-cell activating factor of the TNF ligand family (BAFF) is essential in their physiology. However, in each disease, this is restricted to a subgroup of patients. Based on experiments in mice, and validated in humans, this new cytokine has been highlighted. Excessive production of BAFF alters immune tolerance by rescuing self-binding B-cells. Overexpression in mice leads to autoimmune manifestation, and BAFF levels are elevated in the serum of autoimmune patients. Similar abnormalities occur in chronic lymphocytic leukemia. Recent works suggest that antagonizing the protein (or competing for its receptors) is relevant to the treatment. Advances in our understanding of the BAFF system offers the opportunity to improve our therapeutic approach.
17469102 Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rhe 2007 May OBJECTIVE: To study the role of shared epitope (SE) susceptibility genes, alone and in combination with tobacco smoking and other environmental risk factors, for risk of subtypes of rheumatoid arthritis (RA) defined by the presence or absence of serum antibodies against cyclic citrullinated peptides (CCPs). METHODS: To address these issues, a nationwide case-control study was conducted in Denmark during 2002-2004, comprising incident cases of RA or patients with recently diagnosed RA (309 seropositive and 136 seronegative for IgG antibodies against CCP) and 533 sex- and age-matched population controls. Associations were evaluated by logistic regression analyses, in which odds ratios (ORs) served as measures of relative risk. RESULTS: Compared with individuals without SE susceptibility genes, SE homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95% confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA (OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects were observed, with markedly increased risks of anti-CCP-positive RA in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154), heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE noncarriers who were not exposed to these environmental risk factors. CONCLUSION: Persons who are homozygous for SE susceptibility genes, notably those who are also exposed to environmental risk factors, have a markedly and selectively increased risk of anti-CCP-positive RA. A distinction between anti-CCP-positive RA and anti-CCP-negative RA seems warranted, because these RA subtypes most likely represent etiologically distinct disease entities.