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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
16807698 The antioxidants curcumin and quercetin inhibit inflammatory processes associated with art 2006 Apr OBJECTIVE: Curcumin and quercetin are antioxidant molecules with anti-proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these agents using four assays of inflammatory aspects of arthritis. METHODS: Crystal-induced neutrophil activation was measured by luminol-dependent chemiluminescence. Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of the matrix metalloproteinases collagenase and stromelysin was measured by Northern Blot analysis. Angiogenesis was measured using the chorioallantoic membrane of the chick embryo. RESULTS: Both agents inhibited neutrophil activation, synoviocyte proliferation and angiogenesis. Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay. CONCLUSION: These studies suggest that curcumin and to a lesser extent quercetin may offer therapeutic potential for the treatment of crystal-induced arthritis or rheumatoid arthritis.
18821672 Tumor necrosis factor alpha drives cadherin 11 expression in rheumatoid inflammation. 2008 Oct OBJECTIVE: Cadherin 11 expressed on fibroblast-like synoviocytes (FLS) plays a key role in normal synovial architecture. The purpose of this study was to examine the expression of cadherin 11 in human synovitis. METHODS: Cadherin 11 expression in synovial biopsy samples from patients with various types of arthritis and in lung biopsy samples from patients with interstitial pneumonitis (IP) was examined by immunostaining. The regulation of cadherin 11 expression in human FLS was assessed by quantitative reverse transcription-polymerase chain reaction analysis and Western blotting. Therapeutic modulation of synovial cadherin 11 was assessed before and after effective antiinflammatory therapy. RESULTS: Abundant staining for cadherin 11 was seen in the intimal lining layer and the synovial sublining in inflamed tissues, with discrete staining in noninflammatory osteoarthritic (OA) tissues. The pattern and degree of immunostaining were similar in tissues from patients with rheumatoid arthritis (RA), nonpsoriatic spondylarthritis (SpA), psoriatic arthritis (PsA), and inflammatory OA. Clear staining for cadherin 11 was also observed in lung tissues from RA-associated IP and idiopathic IP patients, but was very limited in normal lung tissue. Cadherin 11 staining correlated strongly with the degree of inflammatory infiltration of the tissue, as well as with the C-reactive protein level and the erythrocyte sedimentation rate in RA patients. In vitro, cadherin 11 expression by FLS was consistently up-regulated by tumor necrosis factor alpha (TNFalpha) at the protein, but not the messenger RNA, level. Cadherin 11 staining in vivo was strongly down-regulated by prednisone treatment in RA patients and by TNFalpha blockade in SpA patients. CONCLUSION: Cadherin 11 expression is regulated by mediators of inflammation, such as TNFalpha. Since cadherin 11 plays an important role in cartilage destruction in experimental arthritis, down-modulation of cadherin 11 by potent antiinflammatory therapies in humans with arthritis may contribute to halting cartilage damage.
18982329 The destruction evaluation in different foot joints: new ideas in collagen-induced arthrit 2009 Apr Collagen-induced arthritis (CIA) has been widely used as the animal model of rheumatoid arthritis since 1977, while till now, no paper has depicted the destruction characteristics in different foot joints. In this study, we observed the differences among the foot joint destruction process of CIA to elucidate further the pathological process of this model. CIA was induced in male Wistar rat immunized with bovine type II collagen and Freund's incomplete adjuvant. Radiological studies were performed 1, 2, 4, 6, and 8 months after the second immunization to follow the development of disease. At last, all the animals were killed and histological research was performed. In the histological observation, three main types of joint destructions such as subchondral side erosion, external joint erosion and the cartilaginous fusion of articular cartilage were identified. All these destruction forms exist in one joint or several different joints. Furthermore, we found that tartrate-resistant acid phosphatase (TRAP) stain-positive cells participated in the destruction of articular cartilage. These new findings showed that in the disease process of the CIA model, different foot joints show different destruction characteristics and cartilaginous fusion of foot joints is another typical pathological characteristic.
17505290 Can exercise influence low bone mineral density in children with juvenile rheumatoid arthr 2007 Summer PURPOSE: Low bone mineral density (BMD) is a common secondary condition associated with juvenile idiopathic arthritis (JIA). The purpose of this review was evaluate the literature pertinent to designing an effective, safe weight-bearing exercise program to reduce the risk of low BMD in children with JIA. SUMMARY OF KEY POINTS: Thirty-seven articles on the risk of low BMD and children with JIA, weight-bearing interventions to improve BMD in healthy children, or safety and efficacy of exercise interventions with children with JIA were critiqued on the basis of their design. Three highly rated studies confirmed the multifactorial nature of low BMD in children with JIA, two highly rated studies support the efficacy of weight-bearing interventions for increasing BMD in children who are healthy, and one moderately rated study demonstrated the safety of low impact exercise by children with JIA. STATEMENT OF CONCLUSIONS AND RECOMMENDATIONS FOR CLINICAL PRACTICE: Weight-bearing activities should be included in exercise programs for individuals with JIA, although more research is needed to determine the amount, duration, and frequency of weight-bearing activity needed to reduce the risk for low BMD.
17343254 Potential triggering infections of reactive arthritis. 2006 Nov OBJECTIVES: The aim of the study was to investigate possible triggering infections causing reactive arthritis (ReA) of urogenital origin. METHODS: One hundred and twenty ReA patients, 85 control group patients with other arthritides (61 with rheumatoid arthritis, 13 with osteoarthritis, and 11 with microcrystal arthritis), and 52 healthy persons were tested for urogenital tract inflammation and several infectious agents. Ligase chain reaction was used for detection of Chlamydia trachomatis (CT). Genital mycoplasmas Ureaplasma urealyticum (Uu) and Mycoplasma hominis (Mh) were tested using the Mycoplasma Duo Test (MDT). Only titres greater than 10(4) CCU/mL were accepted as pathogenecity threshold levels for Uu. RESULTS: Inflammation of the urogenital tract (most frequently urethritis in men and cervicitis in women) was found in 95% of patients with acute ReA. Possible causative pathogens were identified in 58% of ReA patients. CT was found in 29%, Uu in 21%, and Mh in 8% of patients with ReA. While CT and Uu were found more often in HLA-B27-positive than in HLA-B27-negative patients, this was statistically proved only for CT. In ReA males Uu was found four times more frequently than in men with other arthritides. CONCLUSIONS: In active ReA of urogenital origin, inflammation of the urogenital tract is found in the majority of patients. Although CT is the main microorganism associated with urethritis in men and cervicitis in women, mycoplasmas, especially Uu, may be possible aetiological factors for ReA.
17498049 Synovial mast cells: role in acute and chronic arthritis. 2007 Jun Mast cells reside in the normal synovium and increase strikingly in number in rheumatoid arthritis and other joint diseases. Given the broad spectrum of activity of this lineage, it has for decades been considered probable that mast cells are involved in the pathophysiology of synovitis. Recent work in murine arthritis has substantiated this suspicion, showing that mast cells can contribute importantly to the initiation of inflammatory arthritis. However, the role of the greatly expanded population of synovial mast cells in established arthritis remains unknown. Here we review the current understanding of mast cell function in acute arthritis and consider the potentially important influence of this cell on key processes within the chronically inflamed synovium, including leukocyte recruitment and activation, fibroblast proliferation, angiogenesis, matrix remodeling, and injury to collagen and bone. We also consider recent evidence supporting an immunomodulatory or anti-inflammatory role for mast cells as well as pharmacologic approaches to the mast cell as a therapeutic target in inflammatory arthritis.
18519150 The development of inflammatory arthritis and other rheumatic diseases following stem cell 2009 Aug OBJECTIVES: Despite the use of stem cell transplantation (SCT) to treat inflammatory arthritis and other rheumatic diseases, case reports of the paradoxical development of these diseases after SCT are appearing. Three cases of inflammatory arthritis developing after SCT were seen at our institution, leading to a literature review to determine the association between SCT and the de novo development of rheumatic conditions. METHODS: Using PubMed and manual searches of references from pertinent articles, the literature pertaining to the onset of rheumatic conditions following SCT was identified. RESULTS: Case reports detailing the onset of rheumatoid arthritis, HLA-B27-related spondyloarthropathy, psoriatic arthritis, systemic lupus erythematosus, vasculitis, eosinophilic fasciitis, antiphospholipid antibody syndrome, as well as polyarthritis related to intercedent viral infection were identified. Failure of transmission of autoimmune disease from donor to recipient in 2 case reports is also summarized. CONCLUSIONS: The incidence of rheumatic disease development after SCT is unknown, and reported cases may simply reflect those patients who were predisposed to disease development in the first place. However, immunologic manipulation during the SCT process raises the question of whether there is an increased propensity to develop autoimmune disease posttransplant. Clinical vigilance in the recognition of phenotypic changes and clinical events occurring after SCT which may represent new autoimmune phenomena is required.
17269967 Caffeine consumption and methotrexate dosing requirement in psoriasis and psoriatic arthri 2007 Feb BACKGROUND: Recent animal and human studies have suggested that the therapeutic benefit of methotrexate in the treatment of rheumatoid arthritis may be substantially reduced in patients who are concomitantly consuming caffeine. Here, we aimed to investigate the effect of caffeine consumption on the methotrexate dosing requirements in patients with psoriasis and psoriatic arthritis. METHODS: One hundred and fifty patients with diagnoses of psoriasis or psoriatic arthritis were surveyed for their current weekly methotrexate dosage and their usual daily consumption of caffeine. RESULTS: Seventy-five of the patients given the survey responded; of these, 11 were eliminated because they did not report their methotrexate dosage or were no longer taking methotrexate. Of the remaining 64 patients, no correlation was found between the methotrexate dosage needed for disease maintenance and the amount of caffeine consumed. CONCLUSIONS: Our findings suggest that caffeine does not affect methotrexate dosage requirements in patients with psoriasis and psoriatic arthritis. These results do not rule out an effect of caffeine in other inflammatory diseases treated with methotrexate.
18021503 Methods to develop arthritis and osteoporosis measures: a view from the National Committee 2007 Nov OBJECTIVE: Performance measurement at various levels of the health care system promotes improved processes that can result in the provision of more consistent and effective care. This chapter articulates the methodology and criteria utilized in measures development to ensure accountability and serve the information needs of physicians, health care systems, health plans and consumers, using arthritis and osteoporosis as example conditions. METHODS: Observational studies conducted to assess the validity and feasibility of performance measures focused on arthritis and osteoporosis. Clinical expert panels were convened to develop measure specifications based on guidelines and evidence supporting critical aspects of care. The aspects of care that were assessed included: DMARD utilization for patients with rheumatoid arthritis; appropriate gastrointestinal prophylaxis for patients utilizing NSAIDS; comprehensive osteoarthritis care; comprehensive symptom assessment and medical management of woman over 65 years who experienced a bone fracture. RESULTS: The implementation of performance measures for key aspects of arthritis and osteoporosis care is challenged by the availability of administrative data. However, potential for improvement is evident in each of the areas studied. CONCLUSION: The key challenge to the feasibility of arthritis performance measures is the lack of administrative data to identify the eligible population. Administrative data capture suffers as a result of under-coding and under-recognition of arthritis. Consensus around a single set of measures creates a powerful tool for focusing on key components of care as a basis for quality improvement and allows for a valid comparison of care within and across health care settings.
17408208 Unique approach offers guidance to patients with low-prevalence/ high-cost conditions. 2007 Feb A unique intervention delivers behavioral health support to patients with less prevalent, but high-cost conditions. Not nearly as many patients suffer from Crohn's disease or rheumatoid arthritis as diabetes, but Newark, NJ-based Horizon Blue Cross and Blue Shield believes it can nonetheless improve care for these types of patients-and recoup an ROI--by providing them with an intervention that emphasizes psychosocial support.
16775617 Association of two functional polymorphisms in the CCR5 gene with juvenile rheumatoid arth 2006 Sep Juvenile rheumatoid arthritis (JRA) is mediated by Th1-immune responses. In children with JRA, synovial T cells express high levels of the Th1-chemokine receptor CC chemokine receptor 5 (CCR5), which has been implicated in susceptibility to rheumatoid arthritis. To test the hypothesis that genetic variation in CCR5 is associated with susceptibility to JRA, we analyzed patterns of variation in the 5'cis-regulatory region of CCR5 in 124 multiplex families from a JRA-affected sibpair registry. After sequencing the upstream region of CCR5, variants were tested for association with JRA by transmission disequilibrium testing. A single nucleotide polymorphism, C-1835T, was significantly undertransmitted to children with early-onset JRA (P<0.01). C-1835T was genotyped in 424 additional simplex and multiplex families. CCR5-1835T allele was undertransmitted in the cohort of all probands with JRA (P<0.02), as well as in those with early-onset (P<0.01) or pauciarticular JRA (P<0.05). Another variant, a 32-bp deletion in the open reading frame of CCR5 (CCR5-Delta32) was also tested in approximately 700 simplex and multiplex families. CCR5-Delta32 was also significantly undertransmitted to probands with early-onset JRA (P<0.05). Both variants are in regions under natural selection, and result in functional consequences. Our results suggest these CCR5 variants are protective against early-onset JRA.
18528725 Deterioration of lung function is associated with presence of IgM rheumatoid factor and sm 2008 Aug Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according to gender, age, height, and weight. The yearly changes in VC and DLco were calculated, Delta VC and Delta DLco, respectively. IgM RF was measured at the beginning of the study. Smoking was defined as having ever smoked. Statistically significant deterioration of VC and DLco in patients with circulating IgM RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association and whether the presence of IgM RF in smoking patients with SSc actually confers an increased risk of pulmonary damage remains to be determined.
18810481 Selecting highly sensitive non-obese diabetic mice for improving the study of Sjögren's s 2009 Jan BACKGROUND: Non-obese diabetic (NOD) mice are a commonly used murine model for the study of Sjögren's syndrome. However, variations in susceptibility to the disease among the mice has often yielded less stable results. Based on the correlation between the pathological changes and the tear tests, we attempt to establish a simple screening procedure to assure the validity of experimental results by excluding those mice with poor susceptibility to dry eyes. METHODS: Seventy male NOD mice were recruited. The tear film break-up test (BUT) and the phenol red cotton thread test (CTT) were implemented while the mice were under anesthesia. The mice were divided into four groups (grades 1 to 4) based on their BUT readings, and four similar groups based on CTT measurements. Tear samples in each grade were collected for IL-1beta detection with ELISA. The lacrimal glands and conjunctiva of the mice were used to detect the levels of leucocyte common antigen (LCA). LCA-Positive staining was considered as the "gold standard" in the receiver operating characteristic curve (ROC curve) analysis. C57BL/6 mice were used as wild-type controls. RESULTS: There were 13 (18.57%), 43 (61.43%), 10 (14.29%) and 4 (5.71%) mice in grades 1, 2, 3 and 4 by BUT test, and 34 (48.57%), 15 (21.43%), 14 (20.00%) and 7 (10.00%) in grades 1, 2, 3 and 4 by CTT test respectively. Fifty-one out of the 70 mice (72.86%) were detected LCA-positive, and they were mainly in grades 1 and 2 of both the BUT and CCT grading systems. ELISA showed significant variances of IL-beta levels among the four groups (p < 0.01), with much lower IL-beta levels in group 3 and 4 when both BUT and CTT were used for grouping. The tear IL-beta level in the wild-type mice was similar to those of the grade 4 mice, using either BUT or CTT for grouping. The ROC curve analysis provided optimal cutting lines, which were 2 seconds in BUT readings and 4 mm/min in CTT measurements respectively. CONCLUSION: BUT and CTT tests are useful methods in screening high susceptible NOD mice. Cutting lines at BUT < or = 2 seconds and CTT < or = 4 mm/min provide a good balance between the assurance of susceptibility and the maximization of use of NOD mice for the study of Sjögren's syndrome.
17603248 Cryofibrinogenemia associated with Sjögren's syndrome: a case of successful treatment wit 2007 Cryofibrinogenemia (CF) has not been often reported as a complication of various rheumatic diseases. We describe a 44-year-old woman with CF associated with Sjögren's syndrome (SS), who developed digital necrotic ulcerations and purpura of the lower legs. Cryoprecipitate was detected in her plasma, and immunoelectrophoresis showed that the cryoprecipitate was cryofibrinogen. Alprostadil was intravenously administered, but the ulceration was aggravated. Subsequently, administration of high-dose prednisolone (PSL) at 60 mg/day was started, and the ulceration remarkably improved. Cryofibrinogen, detected before the administration of high-dose PSL, was negative after PSL. This is the first case presentation of CF associated with SS successfully treated with high-dose corticosteroid.
17127420 Sjögren's syndrome (SjS)-like disease of mice: the importance of B lymphocytes and autoan 2007 Jan 1 Sjögren's syndrome (SjS) is a systemic autoimmune disease in which an immunological attack against the salivary and lacrimal glands results, respectively, in severe dry mouth and dry eye diseases. Although a CD4+ T lymphocyte population is an integral component in the pathogenesis of SjS, recent studies have focused on the importance the B lymphocyte plays in both the pre-clinical and clinical phases of the disease process. To understand the molecular and cellular mechanisms involved in SjS, numerous mouse models that mimic major clinical manifestations of the human disease have been developed. Studies have begun to define the genetics, the nature of the autoimmune response towards the salivary and lacrimal glands, as well as the possible mechanisms for effecting glandular dysfunction, thereby establishing insights to new intervention therapies. Not surprising, the B cell is taking center stage. Here, we present an in-depth discussion of how B cell populations may be involved in orchestrating or determining exocrine gland dysfunction.
17516374 [Diagnostics of Sjögren's syndrome by means of anti-alpha-fodrin antibody]. 2007 May BACKGROUND: Sjögren's syndrome (SS) is a common connective tissue disease concerning 0.5 % of the white population. Typical symptoms are dry eyes and a dry mouth. The diagnostics of SS often are difficult, especially during early stages of the disease as long as the leading symptoms have not yet fully developed. Previously employed serum antibodies have neither been sensitive nor specific enough to be able to differentiate SS from different rheumatic diseases. We report on a patient with relapsing corneal erosions. In his case we have been able to support the diagnosis of SS by detecting the anti-alpha-fodrin-antibody as well as antinuclear antibodies. CASE REPORT: The patient appeared with incomplete closure of the eyelids and corneal ulcers on both eyes. Smears of the conjunctivae from both eyes were sterile. Schirmer's test indicated a decrease in tear production with 5 mm in the right eye and a normal tear production with 19 mm in the left eye. Three months before, the results of this test had been even more pronounced with 1 mm and 3 - 4 mm, respectively. Additionally the patient described relapsing erosions and a dry mouth. We then examined his blood to help diagnose SS. Results were negative for rheumatoid factor, anti-Ro/SSA antibody and anti-La/SSB antibody, but positive for anti-nuclear-antibodies. In order to spare the patient an invasive biopsy we examined the anti-alpha-fodrin-antibody which was positive. CONCLUSION: Even with negative anti-Ro/SSA and anti-La/SSB antibodies the positive anti-alpha-fodrin-antibody supported the diagnosis of SS. Therefore, we consider it a useful addition to the diagnostics previously employed in the diagnosis of SS (Schirmer's-test, anti-Ro/SSA-AK, anti-La/SSB-AK, rheumatoid factor, eventually biopsy).
17458680 Adult Still's disease associated with cytomegalovirus infection. 2007 Apr A 77-year-old woman was admitted to our hospital complaining of high fever. The physical examination on admission indicated no abnormality. Although several antibiotics were administered, the spiking high fever was not alleviated. Two weeks after admission a macular rash appeared, and a high concentration of serum ferritin was observed. At this point, Still's disease was suspected, and the patient was referred to Nagasaki University Hospital. During the prescribed course of prednisolone, hepatic enzymes gradually increased to high titers accompanied by a positive test for cytomegalovirus (CMV) antigen. The CMV antigen disappeared after ganciclovir administration, and the concentration of serum ferritin decreased after steroid administration. In this report, we attempt to portray the relation between the pathogenesis of adult-onset Still's disease and the presence of CMV antigen.
17899309 Clinical and laboratory profiles of systemic lupus erythematosus associated with Sjögren 2008 Mar This study aims to investigate the clinical and laboratory features of systemic lupus erythematosus (SLE) patients associated with Sjögren syndrome (SS) in China, as well as its similarities to and differences from SLE patients without SS. A group of 542 consecutive unselected SLE patients was recruited. Diagnosis of SLE was made according to 1997 revised American College of Rheumatology SLE criteria; SS was diagnosed using the American-European classification criteria. Clinical and laboratory parameters in SLE patients with SS (SLE-SS) were compared with those in SLE patients without SS (SLE-no SS). Overall, SS was identified in 35 SLE patients (6.5%); the onset of SS preceded the development of SLE in 17 of them (48.6%). Compared with the SLE-no SS group (35.8 +/- 10.5 years), patients with SLE-SS (41.3 +/- 11.6 years) were significantly older (P = 0.003), had a higher frequency of anti-Ro/SSA, anti-La/SSB, and anti-dsDNA antibodies, but had a significantly lower frequency of renal involvement. This study demonstrates that SLE-SS may be a subgroup of patients with characteristic clinical and laboratory features. To improve the treatment outcomes in SLE-SS patients, more specific treatment should be applied based on those factors.
17162364 Genetic basis of Sjögren's syndrome. How strong is the evidence? 2006 Jun Sjögren's syndrome (SS) is a late-onset chronic autoimmune disease (AID) affecting the exocrine glands, mainly the salivary and lachrymal. Genetic studies on twins with primary SS have not been performed, and only a few case reports describing twins have been published. The prevalence of primary SS in siblings has been estimated to be 0.09% while the reported general prevalence of the disease is approximately 0.1%. The observed aggregation of AIDs in families of patients with primary SS is nevertheless supportive for a genetic component in its etiology. In the absence of chromosomal regions identified by linkage studies, research has focused on candidate gene approaches (by biological plausibility) rather than on positional approaches. Ancestral haplotype 8.1 as well as TNF, IL10 and SSA1 loci have been consistently associated with the disease although they are not specific for SS. In this review, the genetic component of SS is discussed on the basis of three known observations: (a) age at onset and sex-dependent presentation, (b) familial clustering of the disease, and (c) dissection of the genetic component. Since there is no strong evidence for a specific genetic component in SS, a large international and collaborative study would be suitable to assess the genetics of this disorder.
16638372 Sjögren syndrome and systemic lupus erythematosus are distinct conditions. 2006 Jan 27 Sjogren syndrome (SS) and systemic lupus erythematosus (SLE) are both collagen vascular diseases that can be accompanied by Ro antibodies. Clinical evidence suggests that they are wholly distinct diseases. SS is strongly linked to lymphoma while lupus is not. SS patients do not commonly exhibit photosensitivity even though anti-Ro antibodies circulate in their blood; SLE patients generally exhibit photosensitivity. SS does not respond to hydroxychloroquine in a reproducible fashion whereas SLE does. SS has not been linked to parvovirus B19, but SLE has. However, SS and SLE do have similarities. Their autoantibody profiles are similar. They effect women more than men and have similar HLA haplotypes and autoantibodies; this is not likely coincidence but it may not clinically relevant.