Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 18975171 | Inhibitory effects of plant extracts on adjuvant-induced arthritis. | 1997 Aug | Twenty seven plant extracts were selected on the basis of ancient literature search for rheumatoid arthritis or similar syndrome. Methanol extract of each plant was prepared and administered orally to rats everyday at a dose of 200 mg/kg/day. Experimental arthritis was induced by subplantar injection of heat-killedMycobacterium butyricum to right hind paw of rats. This treatment provoked swelling of the treated paw in two phases, acute primary swelling and secondary arthritic swelling. An inhibition of secondary swelling was considered to be antiarthritic activity. Several plant methanol extracts such asAkebia quinata (caulis),Ephedra sinica (herba) andSophorae subprostrata (radix) were found to show significant inhibitory activity against secondary swelling at the dose tested. Our results strongly suggested an antiarthritic potential of these plant extracts. | |
| 15348859 | Morphological and mechanical study on the effects of experimentally induced inflammatory k | 1998 Aug | Inflammatory knee arthritis was induced by intraarticular injection of carrageenan twice a week for a total of 6 weeks in New Zealand White rabbits and the effects of the arthritis on the morphological and mechanical properties of the adjacent femur and tibia were evaluated 8 weeks after the first injection. Carrageenan-induced knee arthritis resulted in severe osteopenic changes and a dramatic decrease in bone strength of the entire ipsilateral femur and tibia, including the femoral head and distal tibia, but not the contralateral femur and tibia and the remote humerus. The osteoporotic changes of the adjacent bones of the inflammatory arthritic knee are the basis for the reduced mechanical strength of these bones. These findings may have clinical significance with regard to the mechanisms and consequences of osteoporotic changes in patients with rheumatoid arthritis. | |
| 9396373 | [Two cases with SLE and MCTD developed after a long period of chronic arthritis that was i | 1997 Oct | In order to discuss the diversity of clinical features and the difficulty in diagnosis of children with juvenile rheumatoid arthritis (JRA), we present two cases who have documented the development of systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) after a long period of disease characterized only by arthritis that was initially diagnosed as JRA. The first case was a girl diagnosed for her arthritic joints as polyarticular JRA at 15 years of age. At onset, she had Raynaud phenomenon but autoantibodies such as anti-nuclear antibody (ANA), anti-DNA antibody, and rheumatoid factor were negative. Five years after onset, she became ANA positive and 3 years later she became pregnant. During her pregnancy, she became positive for anti-DNA antibody without any signs of nephritis. One month after the delivery, however, she developed butterfly rash, carditis, nephritis, and was diagnosed as SLE. No destructive changes were observed in her joints though arthritis continued for 8 years form onset to pregnancy. The second case was a 3 years old girl who was diagnosed as polyarticular JRA. Treatment by aspirin induced complate remission after one year from the onset. However, 10 years after that remission, she developed Raynaud phenomenon and arthralgia in her knees and hip joints. Her laboratory findings showed hypergammaglobulinemia, positive ANA, positive anti-DNA antibody, positive anti-RNP antibody. She was eventually diagnosed as MCTD when she was found to have polymyositis by EMG and serum CK. In the present paper, two cases imply the difficulty in diagnosing JRA and diversity of rheumatic diseases such as JRA, SLE and MCTD. Closer and longer period of observation is essential for the JRA patients with nondestructive arthritis. | |
| 9346269 | Sulphasalazine therapy in chronic uveitis of children with chronic arthritis. | 1997 Jun | Four children with chronic arthritis (3 juvenile rheumatoid arthritis and 1 juvenile ankylosing spondylitis) and poorly controlled chronic uveitis, were given sulphasalazine (SASP) therapy for a mean period of 3.3 years. Three patients showed an excellent response, as evidenced by a reduction of inflammatory cells in the anterior chamber of the eyes and improvement of visual acuity. The response occurred after a mean of 7.7 weeks. These data suggested SASP therapy may have a role in the treatment of chronic anterior uveitis in children with chronic arthritis. | |
| 9228145 | Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthri | 1997 Jul | OBJECTIVE: To evaluate quantitative or qualitative differences in synovial fluid (SF) cytokine levels among patients with systemic juvenile rheumatoid arthritis (JRA), antinuclear antibody positive pauciarticular JRA, or adult RA. METHODS: SF levels of interleukin 1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra) IL-11, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptor 1 (sTNFR1), leukemia inhibitory factor (LIF), all measured by immunoassays, and of IL-6, measured with a bioassay using B9 cells, were evaluated in 11 patients with systemic JRA, 24 with pauciarticular JRA, and 22 adult patients with RA. RESULTS: SF IL-6 levels were significantly higher in patients with systemic JRA than patients with pauciarticular JRA (p = 0.003) or RA (p = 0.002). IL-1alpha was detectable in 12/24 SF samples from pauciarticular JRA, in 2/22 SF from RA, and in no sample from systemic JRA (p = 0.004 vs RA; p = 0.005 vs systemic JRA). SF IL-11 levels were significantly higher in patients with RA than patients with systemic JRA (p = 0.012) or pauciarticular JRA (p = 0.005). We found no significant differences in SF levels of IL-1beta, IL-1Ra, TNF-alpha, sTNFR1, or LIF. CONCLUSION: In systemic JRA, SF levels of IL-6 are significantly higher than in pauciarticular JRA or in RA; IL-1alpha is present in a significant proportion of patients with pauciarticular JRA, but not in those with RA or systemic JRA. | |
| 11182599 | Direct gene delivery strategies for the treatment of rheumatoid arthritis. | 2001 Mar 1 | Gene therapy offers a novel and innovative approach to the delivery of therapeutic proteins to the joints of patients with arthritis. Several viral vectors, including adenovirus, adeno-associated virus, retrovirus and herpes simplex virus, are capable of delivering exogenous cDNAs to the synovial lining, enabling effective levels of intra-articular transgene expression following direct injection to the joint. The expression of certain gene products has proven to be sufficient to inhibit the progression of disease in animals with experimental arthritis. Non-viral methods of gene transfer, however, are less satisfactory, and are limited by toxicity and transience of expression. Although the principle of direct gene delivery to the joint has been demonstrated, maintaining persistent intra-articular transgene expression remains a challenge. | |
| 9222963 | Progressive pseudorheumatoid dysplasia: report of a family and review. | 1997 Jul | Progressive pseudorheumatoid dysplasia is an inherited skeletal dysplasia with radiographic changes notably in the spine, similar to spondyloepiphyseal dysplasia tarda. There is also articular cartilage involvement which gives it some clinical resemblance to rheumatoid arthritis. We report here on six subjects from one inbred family from Jordan. Based on previously published reports and this one, we review the clinical and radiological features and discuss the genetics and differential diagnosis of the disorder. We suggest the addition of the word "spondyloepiphyseal" to the name adopted by the International Working Group on Constitutional Diseases of Bone, to become "progressive pseudorheumatoid spondyloepiphyseal dysplasia". We also speculate on candidate genes for this disorder. | |
| 9489834 | Expression of macrophage markers by a population of T cells obtained from synovial fluid o | 1998 Feb | OBJECTIVE: To characterize distinctive lymphoid cell populations in the synovial fluid (SF) of patients with juvenile rheumatoid arthritis (JRA) that have the specific ability to display monocytic markers when cultured in vitro. METHODS: Mononuclear cells obtained from SF of patients with JRA and depleted of adherent macrophages were cultured in vitro in RPMI 1640 medium supplemented with only fetal calf serum (FCS). Phenotypic evaluation of these cells was by flow cytometry and immunohistochemical analysis was by specific fluorochrome labeled antibodies. RESULTS: T cells from a JRA subgroup displayed some typical macrophage attributes, i.e., abundant cytoplasm, adherence to plastic, and phagocytosis of latex beads when cultured in vitro. These cells have the ability to survive in culture for several weeks in RPMI 1640 medium containing only 10% FCS. The macrophage-like T cells rosetted with sheep red blood cells and proliferated when stimulated with phytohemagglutinin or anti-CD3, indicating functional T cell responses. CONCLUSION: Our data indicate that a population of T cells obtained from the SF of a subgroup of patients with JRA exhibited characteristics of macrophages, yet retained their CD3 and T cell receptor expression. Whether this promiscuous behavior is caused by malignant transformation of lymphoid precursor cells or is induced by the concerted effect of a myriad of cytokines and growth factors present in the SF remains unknown. The presence of these cells in the SF of 2 patients with JRA with different onset types raises the question of their function and significance in an autoimmune disorder such as JRA. | |
| 9415655 | Preliminary evidence for cyclosporin A as an alternative in the treatment of recalcitrant | 1997 Dec | OBJECTIVE: To evaluate the safety and efficacy of cyclosporin A (CyA) with and without methotrexate (MTX) in refractory juvenile rheumatoid arthritis (JRA) and juvenile dermatomyositis (JDMS). METHODS: Twenty-two patients (17 with JRA, 5 with JDMS) with refractory disease were studied retrospectively. All received CyA at a mean dose of 3.2 mg/kg/day over a mean period of 16 mo (range 6-42). All other medications except nonsteroidal antiinflammatory drugs, prednisone, and hydroxychloroquine were discontinued. In addition, 16/22 patients received concomitant MTX. RESULTS: Improvements in laboratory variables, joint counts, joint swelling, and morning stiffness were observed in most of the children with JRA. Muscle strength increased and muscle enzyme levels decreased in the patients with JDMS. CyA treatment permitted prednisone to be discontinued in 5/20 and reduced by greater than 50% in 10/20 patients. There was no evidence of hepatic or bone marrow toxicity or lymphoproliferative disease. Serum creatinine increased in 13/22 patients, but the actual values all remained within normal limits. CONCLUSION: CyA may be an effective agent in the treatment of refractory JRA and JDMS and concomitant MTX seems to be well tolerated. These preliminary data also suggest that combined CyA/MTX therapy may be associated with further improvement in clinical outcome. | |
| 11717717 | Correlation between osteochondral changes depicted by magnetic resonance imaging and disea | 2001 Jul | PURPOSE: To determine the consequences of the chronic use of systemic corticosteroids in children with juvenile rheumatoid arthritis by means of evaluating osteochondral effects depicted by magnetic resonance imaging. PATIENTS AND METHODS: We reviewed clinical and magnetic resonance imaging findings in 69 children (72 knees) with juvenile rheumatoid arthritis. Two groups were studied. Group I: 34 (49.3%) children had previous or current use of systemic corticotherapy (22 girls; 12 boys; mean age: 11.3 years; mean disease duration: 5.9 years; mean corticotherapy duration: 2.9 years; mean cumulative dose of previous corticosteroids: 5000 mg); Group II: 35 (50.7%) children had no previous use of corticosteroids (27 girls; 8 boys; mean age: 11.7 years; mean disease duration: 5.3 years). The groups were compared statistically. RESULTS: In the group that had received corticotherapy (Group I), osteochondral abnormalities were significantly correlated to long-standing disease (>3.5 years; p<0.001). This correlation was not found in the group that had no previous history of corticotherapy (Group II). No correlations were established between median dose of corticosteroids and magnetic resonance imaging findings. CONCLUSION: It is important to further investigate the long-term intra-articular effects of systemic corticotherapy to ensure that the side effects of the aggressive therapy will not be more harmful for the joints than the symptoms suffered over the natural course of the disease. | |
| 10410276 | Clinical significance of anticardiolipin antibodies in juvenile idiopathic arthritis. | 1999 May | OBJECTIVE: Anticardiolipin antibodies (aCL) have been demonstrated in a large spectrum of autoimmune diseases. However, its occurrence in childhood, in particular in juvenile idiopathic arthritis (JIA), is not well established. The present study addressed the frequency and clinical significance of aCL in a group of JIA patients. METHODS: aCL (IgG and IgM isotypes), antinuclear antibodies (ANA), and rheumatoid factor (RF) were determined in 86 children with JIA (33 systemic, 31 polyarticular and 22 oligoarticular onset type). Thirty-two juvenile systemic erythematosus lupus patients (JSLE) and 52 healthy children formed the control groups. The disease activity and functional status of the JIA patients were scored to study their possible associations with the presence of aCL. RESULTS: Serum aCL levels above the normal range were detected in 28/86 JIA patients (32.5%), 12/32 JSLE patients (37.5%), and 3/52 healthy children (6%). Positive aCL levels were slightly or moderately elevated (usually below 30 GPL and 20 MPL). The presence of aCL was not associated with the presence of ANA or RF. Associations between aCL and clinical parameters, such as disease onset, duration, activity or severity could not be established. No JIA patient had vascular thrombosis, thrombocytopenia or "livedo reticularis". CONCLUSION: aCL occurred in low titers in JIA children, in a similar frequency to that observed in JSLE. No association with JIA clinical parameters or the clinical features classically linked to the antiphospholipid antibody syndrome were observed. | |
| 10377850 | [Amyloidosis. A review]. | 1999 May 24 | Amyloidosis is a heterogenous group of diseases, all characterized by extracellular deposition of amyloid either systemically or localized. Of wellknown diseases are Alzheimer's dementia, AL-amyloidosis (e.g. in multiple myeloma) and AA-amyloidosis (e.g. in rheumatoid arthritis). Amyloid is composed of three components of which the fibrillary component is the basis of amyloid classification. Many types of amyloid have a systemic distribution and give rise to varying symptoms. The diagnosis is based on biopsy, preferably of abdominal subcutis. The prognosis is poor, however, recent investigations on the three-dimensional structure of the P-component provide hope for future therapy. | |
| 10595864 | Medical management of children with juvenile rheumatoid arthritis. | 1999 Nov | One of the most important and changing areas of research in paediatric rheumatology is the optimum approach to the treatment of children with chronic arthritis. Until recently all medications for children with arthritis were nonspecific in terms of our understanding, albeit poor, of the pathogenesis of these diseases. Of current therapies, low dose, once-a-week methotrexate has emerged as the therapeutic agent of choice for children who fail to respond adequately to administration of a nonsteroidal anti-inflammatory drug. Thereby, it has displaced the more traditional slower acting anti-rheumatic drugs, although one or more of them are often combined with methotrexate in the polypharmaceutical approach to childhood arthritis. Better and more specific agents are needed, especially for systemic onset disease, unremitting polyarticular involvement, and certain complications such as resistant chronic uveitis. At this time the introduction of the cyclo-oxygenase 2 inhibitors and etanercept (soluble tumour necrosis factoralpha.p75 fusion protein) may herald an era of more specific and effective therapy. | |
| 9058672 | Severe sore throat as a presenting symptom of adult onset Still's disease: a case series a | 1997 Mar | We describe our experience with 3 cases and a literature review examining whether sore throat is an early manifestation of adult onset Still's disease (AOSD). From our review of 341 cases in the English literature we noted that 69% of all reported patients displayed sore throat early in the disease course. We propose that sore throat be considered an important early diagnostic manifestation of AOSD because it appears useful in identifying patients in their first month of illness. | |
| 10528210 | IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collage | 1999 Nov 1 | Anti-TNF-alpha treatment of rheumatoid arthritis patients markedly suppresses inflammatory disease activity, but so far no tissue-protective effects have been reported. In contrast, blockade of IL-1 in rheumatoid arthritis patients, by an IL-1 receptor antagonist, was only moderately effective in suppressing inflammatory symptoms but appeared to reduce the rate of progression of joint destruction. We therefore used an established collagen II murine arthritis model (collagen-induced arthritis(CIA)) to study effects on joint structures of neutralization of either TNF-alpha or IL-1. Both soluble TNF binding protein and anti-IL-1 treatment ameliorated disease activity when applied shortly after onset of CIA. Serum analysis revealed that early anti-TNF-alpha treatment of CIA did not decrease the process in the cartilage, as indicated by the elevated COMP levels. In contrast, anti-IL-1 treatment of established CIA normalized COMP levels, apparently alleviating the process in the tissue. Histology of knee and ankle joints corroborated the finding and showed that cartilage and joint destruction was significantly decreased after anti-IL-1 treatment but was hardly affected by anti-TNF-alpha treatment. Radiographic analysis of knee and ankle joints revealed that bone erosions were prevented by anti-IL-1 treatment, whereas the anti-TNF-alpha-treated animals exhibited changes comparable to the controls. In line with these findings, metalloproteinase activity, visualized by VDIPEN production, was almost absent throughout the cartilage layers in anti-IL-1-treated animals, whereas massive VDIPEN appearance was found in control and sTNFbp-treated mice. These results indicate that blocking of IL-1 is a cartilage- and bone-protective therapy in destructive arthritis, whereas the TNF-alpha antagonist has little effect on tissue destruction. | |
| 11604601 | Lyme disease in children. | 2001 Sep | Lyme borreliosis is a multisystem disorder caused by Borrelia burgdorferi and transmitted by ticks in the northern hemisphere. The disease is common in children. In addition to frequently recognized manifestations such as erythema migrans, neuroborreliosis, and Lyme arthritis, rarer manifestations, including eye and ear disease, are increasingly understood. Clinical diagnosis is supported by serologic confirmation. Improvement of laboratory methodology, especially polymerase chain reaction-based tests, is continuing. Actual treatment recommendations based on controlled studies reflect expanding scientific knowledge. In the United States, license of a vaccine to prevent infection in children is awaited. Lyme borreliosis is an intriguing human example of bacterial persistence in the presence of the host immune system. Chronic Lyme arthritis is a model of chronic arthritis resembling forms of arthritis of unknown cause, such as rheumatoid arthritis and juvenile idiopathic arthritis. | |
| 9153561 | Multiple congenital anomalies associated with weekly low-dose methotrexate treatment of th | 1997 May | This report describes an infant with multiple congenital anomalies born to a 20-year-old mother with juvenile rheumatoid arthritis who had been taking weekly low-dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low-dose MTX treatment. | |
| 11892913 | Angiogenesis: a therapeutic target in arthritis. | 2001 Aug | A variety of pharmacological strategies are being subjected to clinical trial to inhibit neovascularization of solid tumors. Increased angiogenesis is also a key component of synovitis and bone modeling in arthritis. Molecular mechanisms and pathological consequences of blood vessel growth in arthritis are now being elucidated. Preclinical studies of angiogenesis inhibitors in animal models of inflammatory arthritis support the hypothesis that inhibition of neovascularization may reduce inflammation and joint damage. Clinical data are consistent with these models being predictive of efficacy in rheumatoid arthritis. However, controlled studies of specific anti-angiogenic agents in human arthritis remain limited. Further studies are required to demonstrate that pharmacological agents can effectively inhibit articular angiogenesis, and ameliorate inflammation and subsequent joint damage. Potential toxicity of angiogenesis inhibitors in reproduction, growth and development and wound repair may be circumvented by short-term or local application, or by targeting molecular mechanisms that are specific to pathological rather than physiological angiogenesis. | |
| 18432737 | Collagen-induced arthritis. | 2001 May | Collagen-induced arthritis (CIA) is an experimental autoimmune disease that can be elicited in susceptible strains of rodents (rat and mouse) and nonhuman primates by immunization with type II collagen (CII), the major constituent protein of articular cartilage. Because of the important similarities between CIA and rheumatoid arthritis, this experimental model of autoimmune arthritis has been the subject of extensive investigation in several laboratories. Protocols for CIA are described in this unit for both the mouse model and the rat model. In addition, protocols are included for the purification of CII from bovine articular joints and chicken sternums, for the purification of collagen a1(II) chains, and for the purification of fragments of these chains following cyanogen bromide (CNBr) digestion. The preparation of CII is a time-consuming procedure but is usually required because of the scarcity and expense of commercial sources of purified native CII. In addition, support protocols are provided for assessing the severity of inflammation following CIA and for measuring B and T cell responses to CII. | |
| 10411542 | Suppression of arthritic bone destruction by adenovirus-mediated csk gene transfer to syno | 1999 Jul | Rheumatoid arthritis (RA) is characterized by a chronic inflammation of the synovial joints resulting from hyperplasia of synovial fibroblasts and infiltration of lymphocytes, macrophages, and plasma cells, all of which manifest signs of activation. Recent studies have revealed the essential role of osteoclasts in joint destruction in RA. Src family tyrosine kinases are implicated in various intracellular signaling pathways, including mitogenic response to growth factors in fibroblasts, activation of lymphocytes, and osteoclastic bone resorption. Therefore, inhibiting Src activity can be a good therapeutic strategy to prevent joint inflammation and destruction in RA. We constructed an adenovirus vector carrying the csk gene, which negatively regulates Src family tyrosine kinases. Csk overexpression in cultured rheumatoid synoviocytes remarkably suppressed Src kinase activity and reduced their proliferation rate and IL-6 production. Bone-resorbing activity of osteoclasts was strongly inhibited by Csk overexpression. Furthermore, local injection of the virus into rat ankle joints with adjuvant arthritis not only ameliorated inflammation but suppressed bone destruction. In conclusion, adenovirus-mediated direct transfer of the csk gene is useful in repressing bone destruction and inflammatory reactions, suggesting the involvement of Src family tyrosine kinases in arthritic joint breakdown and demonstrating the feasibility of intervention in the kinases for gene therapy in RA. off |