Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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7842530 | Systemic cytokine measurements: their role in monitoring the response to therapy in patien | 1994 Sep | OBJECTIVE: To determine the value of serial measurements of circulating cytokines in patients with rheumatoid arthritis in response to the introduction of disease modifying anti-rheumatic drugs (DMARDs). METHODS: A prospective 12-week study of 98 patients starting second line therapy with serial measurements of IL1 beta, IL2 receptor, IL6, TNF, and urinary neopterins as well as ESR, CRP and rheumatoid factor. RESULTS: The markers of the acute phase response fell significantly with treatment as did the rheumatoid factor. IL-6 fell in certain sub-groups (significantly so after sulphasalazine SZP) of treated patients, but no other consistent change in circulating cytokine levels was demonstrated. Urinary neopterins rose with therapy. CONCLUSIONS: The measurement of circulating cytokine levels in patients with rheumatoid arthritis is of limited benefit; macrophage function (as measured by urinary neopterins) is initially enhanced by DMARDs in patients with rheumatoid arthritis. | |
1352153 | T cell receptor beta gene polymorphism and rheumatoid arthritis. | 1992 | Susceptibility to rheumatoid arthritis is, in part, conferred by genetic factors. Previous studies have suggested that inheritance of a particular allele of a restriction fragment length polymorphism (RFLP) detected in the T cell receptor beta (TCR beta) gene complex is associated with rheumatoid arthritis (RA). We have specifically tested this hypothesis in ethnically and geographically matched populations of RA patients and controls. We were unable to confirm previous observations of a TCR beta association with RA even after stratifying our study and control populations by HLA type. | |
8156292 | Ultrasonography of the tibialis posterior tendon in rheumatoid arthritis. | 1994 Mar | This work was carried out to assess the frequency of frank rupture of the tibialis posterior tendon (TPT) in RA and to determine if other pathology in the tendon can be correlated with foot deformity. Clinical, radiographic and ultrasonographic signs of TPT pathology were assessed bilaterally in 28 patients with RA and hindfoot involvement. The degree of hindfoot pain, the single-heel-rise test and the tibiocalcaneal angle were assessed clinically. The talometatarsal angle was measured on lateral weight-bearing radiographs. Tendon continuity and thickness were noted on sonography, both in the study group and in a control group of 14 patients. The TPT was significantly thinner in those rheumatoid patients with an abnormal single-heel-rise test when compared to those patients with a normal test (P < 0.001) and to the control group (P < 0.001). The mean thickness in patients with an abnormal test was 1.6 mm, in patients with a normal test it was 2.3 mm and in the controls it was 1.9 mm. In the rheumatoid group thinning of the tendon was significantly correlated (r = -0.33, P < 0.05) with heel valgus as assessed by the tibiocalcaneal angle. It was also significantly correlated (r = 0.31, P < 0.05) with pes planus as assessed by the talometatarsal angle. Only one case of frank rupture of the TPT was identified. There were also significant correlations between TPT thickness and patient age, disease duration and steroid therapy, such that tendon attenuation was associated with increasing age, longer disease and steroid usage. There was no association between TPT thickness and the degree of hindfoot pain.(ABSTRACT TRUNCATED AT 250 WORDS) | |
8594658 | [Matrix metalloproteinase (MMP-9) in patients with rheumatoid arthritis]. | 1995 Oct | MMP-9 degrades type IV collagen, gelatin, type V collagen, and type XI collagen. We measured proMMP-9 and proMMP-9/TIMP-1 complex in sera and joint fluids by sandwich ELISA, and examined immunohistochemically the expression of these proteins in joint tissue from patients with rheumatoid arthritis (RA). ProMMP-9 was purified by the three chromatographic steps from the culture medium of HT1080 cells. Purified proMMP-9 and activated MMP-9 by APMA showed a single band of Mr92000, Mr67000, resectively on gelatin-zymography. We raised two monoclonal antibody colones 2G9, 8G7 against proMMP-9 with BALB/c mice. 2G9 and 8G7 reacted with proMMP-9 on Western blotting, and these clones reacted proMMP-9 and proMMP-9/TIMP-1 complex on sandwich ELISA, specifically. ProMMP-9 concentration in 86 sera (749.4+/-940.2 ng/ml) and 54 joint fluids (4539.9+/-7681.5 ng/ml) from patients with RA was significantly higher than those of patients with osteoarthritis and control. Immunohistochemistry with 2G9 showed that in rheumatoid synovium proMMP-9 localized in neutrophils and monocytes diffusely infiltrated the sublining layer. In addition, osteoclasts in rheumatoid subchondral bone were intensively stained. ProMMP-9 concentration in joint fluids from 39 RA patients was not correlated to stage and class of Steinbrocker and to clinical laboratorial data. But, it was positively correlated to the number of proMMP-9 positive cells in RA synovium (r=0.607) and the score of Roony's diffuse infiltrates of lymphocytes (r=0.720). Our results suggest a role of MMP-9 in joint destraction of RA throughout neutrophils and monocytes, and a regulation of this enzyme by lymphocytes. | |
7619648 | [Keratoconjunctivitis sicca in rheumatoid arthritis: correlation with the autoantibody pat | 1995 Apr | In order to evaluate the autoantibody pattern of subjects affected by rheumatoid arthritis (RA) with clinical features of keratoconjunctivitis, we studied 32 out- and in-patients (26 women, 6 men, average age 52 years, average disease duration 5.5 years) at the Division of Rheumatology, Catholic University of Rome. We found keratoconjunctivitis sicca and xerostomia in 22 (68.75%) patients with RA. Rheumatoid factor was present in 17 (53.1%) patients, antinuclear antibodies (ANA) were observed in 15 (48.4%) patients, and anti-rheumatoid arthritis nuclear antigens (RANA) in 22 (68.7%) patients; anti-SSA antibodies were confirmed in 3 (9.4%) patients and anti-SSB antibodies in 2 (6.2%) patients. None of the patients evidenced anti-U1RNP. Although keratoconjunctivitis sicca and xerostomia correlated significantly with the presence of rheumatoid factor, we found no relationship between these two conditions and ANA or anti-RANA antibodies. The high frequency of keratoconjunctivitis sicca and xerostomia in our RA patients is the expression of extra-articular involvement in this disease and is correlated with the presence of rheumatoid factor. ANA and anti-RANA antibodies may represent aspecific polyclonal activation in RA. | |
8156301 | Detection of cytomegalovirus, Epstein-Barr virus and herpes virus-6 in patients with rheum | 1994 Apr | The frequency of latent viral infection by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and herpes virus-6 (HHV-6) was investigated in patients with RA with or without Sjögren's syndrome (SS) and in normal controls. Virus presence was determined by polymerase chain amplification of DNA isolated from peripheral blood mononuclear or polymorphonuclear cells and/or saliva-derived mononuclear/epithelial cells. Anti-viral antibodies and autoantibodies were also assayed. Patients with RA both with and without SS were found to have a significantly increased frequency of latent viral infection (two-fold higher, P = 0.035 for EBV and seven-fold higher, P = 0.018 for HHV-6) compared to normal controls but only in cells isolated from saliva. The increased frequency of virally infected cells from the saliva of patients with RA, regardless of the SS status, when compared to normal controls may reflect the ongoing inflammatory process, the impact of therapy and/or a less effective local immune responsiveness. | |
8332800 | [Rheumatoid arthritis: echographic study of lesions of the periskeletal soft tissues]. | 1993 May | The role of US was investigated in the study of rheumatoid arthritis, since the method depicts the changes in the periskeletal soft tissues--i.e., where the disorder preferably locates in both its early and late phases. A hundred and fifty-eight patients affected with rheumatoid arthritis according to American Rheumatism Association criteria were examined: the hand (wrist, carpus, metacarpus and fingers), the knee and the foot (metatarsus and toes) were studied in all patients. The study population was divided into two groups according to the time of onset of the disease: in 82 of them (52%) the onset of symptoms dated back to less than a year, while 76 of them (48%) had been suffering for over a year. US appears as the most accurate method to study the early phases of rheumatoid arthritis, for it makes early diagnosis possible, thus allowing the correct treatment to be chosen and preventing the disease from causing the irreversible lesions which progressively disable the patient. In the early phases of rheumatoid arthritis, US detects the exudative effects of synovial inflammation in periskeletal soft tissues. Joint effusions and synovial pannus are also depicted by US, as well as the thickening of tendon sheaths and tendon ruptures and rheumatoid nodules. In the late phases of rheumatoid arthritis, US supports conventional radiology, the latter remaining the irreplaceable method of choice to demonstrate skeletal lesions. Nonetheless, in such phases US yields further information on periarticular soft tissue involvement which no other method would make available--e.g., the presence of effusions, bulgings, synovial pannus, joint cartilage erosions, damaged tendons and sheaths, hypoplasia of the muscles ending on the involved joint and finally periarticular changes. Finally, US proves of great value in the early demonstration of reactivating phases, with unquestionable prognostic advantages. | |
7998894 | Cyclosporine, azathioprine and local therapy for pyoderma gangrenosum. | 1994 | A markedly obese 54 year old woman with seropositive rheumatoid arthritis, anaemia, dyspepsia, controlled hypothyroidism and depression presented with a seven month history of large pyoderma gangrenosum ulcers on the shins. Routine dressings for the ulcers had been ineffective. Her arthritis was being treated with azathioprine and NSAID's. Initial treatment with clobestasol propionate and disodium cromoglycate under occlusion produced only partial healing. Introduction of Cyclosporin A and continuation of topical therapy, with the addition of triamcinolone acetonide injections, led to progressive healing which was complete after seven months. There has been no relapse to date. Cyclosporine can be combined with azathioprine and local therapy for successful treatment of pyoderma gangrenosum. | |
8258242 | Correlation of interleukin-2 receptor and neopterin secretion in rheumatoid arthritis. | 1993 Sep | In rheumatoid arthritis (RA) an immuno dysregulation alters the release of neopterin from human monocytes/macrophages, probably by activation of a feed-back regulation mechanism in pterin metabolism. With the overactivation of T-lymphocytes, the secretion of interleukin-2 and its receptor (IL-2R) is influenced. Investigation on 84 RA patients has shown that this immunoactivation is accompanied by an increased secretion of neopterin and soluble IL-2R in the serum, and that both parameters are very suitable for detection of inflammatory disease activity. The significant correlation between neopterin and IL-2R (r = 0.65; p < or = 0.001) in RA points out a possible connection in pathomechanisms of the immune system. | |
7519956 | Antibodies to synthetic peptide P62 corresponding to the major epitope of rheumatoid arthr | 1994 Aug | Using a synthetic peptide (P62) we have investigated antibodies to rheumatoid arthritis nuclear antigen (RANA) in 58 West African patients with RA, 51 with malaria, 111 with tuberculosis (TB) and 166 healthy controls by ELISA using a synthetic peptide (P62). As in Western populations the RA sera showed significantly increased levels of anti-P62 antibodies though in our study the mean titres were only elevated twofold above the controls. The levels in malaria and TB were normal. Our data extend previous work by showing that raised anti-P62 antibodies is a consistent finding in RA world-wide including indigenous West African patients. | |
8144068 | [Closure of rheumatic palmar perforations of the wrist capsule with a flap of retinaculum | 1993 Sep | In 53 hands with rheumatoid arthritis, bony spurs of the scaphoid and trapezium were found perforating the capsule of the radial wall of the carpal tunnel. After removal of the spurs, the remaining capsular defect was covered by a flap of the flexor retinaculum. The flap is raised from the flexor retinaculum in a width of approximately 15 mm by parallel transverse incisions and is based radially. Then it is brought down to the defect and sutured to the local ligaments. The blood supply of the retinacular flap is well preserved. The flap provides a reliable cover of the capsular defect as well as a smooth gliding surface for the flexor tendons. | |
7551664 | The effects of joint washout and steroid injection compared with either joint washout or s | 1995 Aug | Patients with rheumatoid arthritis attending rheumatology out-patients who had a symptomatic knee effusion were randomly allocated to receive one of three treatments: group I, a steroid injection without washout; group II, a joint washout with normal saline; group III, a joint washout with normal saline and steroid injection. Sixty knees in all were studied. Laboratory parameters for disease activity (erythrocyte sedimentation rate, C-reactive protein) were monitored in all patients prior to the study and at 3 months. Clinical assessment of disease activity (pain, morning stiffness involving the knee, circumference of the knee, walking distance and range of movement) were recorded prior to the study, at 1 month and at 3 months. All three treatments, resulted in a reduction of pain and increased movement. However, patients who had a joint washout alone showed significantly less improvement as compared with the other two groups. Symptomatic improvement was marginally greater in patients following joint washout and injection than in those who had had joint injection alone. The results of the study indicate that the simple procedure of joint aspiration and steroid injection, which can be carried out in the out-patient clinic, provides satisfactory relief of symptoms in rheumatoid patients with knee effusions. Joint washout alone was less beneficial. | |
7945475 | Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study. | 1994 Oct | OBJECTIVE: To evaluate the efficacy and tolerability of oral methotrexate (MTX) in rheumatoid arthritis (RA) in a long-term prospective trial. METHODS: One hundred twenty-three patients with RA who completed a 9-month multicenter randomized trial comparing MTX and auranofin enrolled in this 5-year prospective study of MTX. RESULTS: Significant (P = 0.0001) improvement compared with baseline was noted in all clinical disease variables, functional status, and the Westergren erythrocyte sedimentation rate (ESR). "Marked improvement" occurred in 87 (71%) and 85 (69%) of the patients, respectively, in the joint pain/tenderness index and the joint swelling index at the last evaluable visit. Forty-four patients (36%) withdrew during the study. Eight (7%) withdrew due to lack of efficacy, and 8 (7%) due to adverse experiences, including 1 patient with cirrhosis. At 5 years, 64% of patients were still taking MTX and completed the study. CONCLUSION: This large prospective study of long-term MTX treatment demonstrates sustained clinical response and improvement in the Westergren ESR and functional assessment scores, with an acceptable toxicity profile. | |
8777270 | Resident joint tissues, rather than infiltrating neutrophils and monocytes, are the predom | 1996 Feb | Intraarticular injection of zymosan (1 mg) into the knee joints of male Wistar rats led to infiltration of neutrophils and monocytes, joint swelling and elevation of tumour necrosis factor (TNF-alpha) in joint lavage fluids. Neutrophil infiltration was maximal at 5 h after induction of arthritis but had declined by 24 h post injection. Monocyte infiltration was maximal around the same time as that of the neutrophil infiltration but was sustained through 24 h. Joint swelling was apparent at 1 h but was not maximal until 6 h after induction of zymosan-induced arthritis. The maximum levels of TNF-alpha (150-200 pg of mouse equivalents per joint) in joint fluid preceded the infiltration of neutrophils and monocytes and was maximal at 1-2 h after injection of zymosan but had declined to below 100 pg per joint at 5 h (the time of maximal leukocyte infiltration) and was below the lower limit of detection at 24 h after induction of arthritis. Depletion of neutrophils and monocytes with a rabbit anti-rat leukocyte antibody reduced leukocyte infiltration and the later phase of joint swelling but did not reduce the levels of TNF-alpha in joint fluid. These data indicate that in zymosan-induced arthritis TNF-alpha is produced from the resident joint tissues such as the synovial lining cells rather than infiltrating neutrophils or monocytes. | |
7552069 | Role of antigen presenting cells in rheumatoid arthritis. | 1995 Apr | Histological evidence indicates that activated antigen presenting cells (APC) are present in large numbers within the synovial compartment in rheumatoid arthritis. Their potent function has been demonstrated in vitro using isolated synovial APC populations, although the full picture of which APC populations are involved is still emerging. The ability of these APC to activate T cells which traffic to the joint is likely to play an important role in the maintenance of the synovial inflammatory response. | |
8241598 | Rheumatoid arthritis in a patient with pseudoxanthoma elasticum. | 1993 Jun | Pseudoxanthoma elasticum (PXE) is a rare, inherited disorder of the connective tissue. Possible association of autoimmune thyroiditis and PXE has been suggested, but reports of other autoimmune diseases complicating PXE are rare. We report a case of rheumatoid arthritis (RA) in a patient with PXE. Since the frequency of PXE is likely to be underdiagnosed, further studies to elucidate the true incidence and significance of the association of RA and PXE will be needed. | |
8131352 | The role of adhesion molecules in synovial pannus formation in rheumatoid arthritis. | 1994 Mar | To elucidate the mechanism of cell binding to cartilage, using an immunoperoxidase technique with monoclonal antibodies against adhesion molecules, the pattern of distribution of these molecules at the rheumatoid pannus-cartilage junction has been investigated. Treatment with purified anti-human-monoclonal antibody CD54 anti-(ICAM-1) resulted in membrane staining of most of the large cells infiltrating the synovial tissue and bordering the pannus cartilage junction. When the specimen was treated with purified anti-human-monoclonal antibody CDw49d anti-(VLA-4), purified anti-human-monoclonal antibody CDw49e anti-(VLA-5), most of the cells in the cartilage pannus junction stained, but there were few staining cells against purified anti-human-monoclonal antibody CD11a anti-(LFA-1). There were some anti-ICAM-1 and anti-VLA-5 staining of the chondrocytes at or close to the junction. Human umbilical vein ECBBA1 (ELAM-1) staining was only observed on the endothelial cells of postcapillary venules in the synovial tissue. These results show that the specific adhesion molecules tested may play a role in rheumatoid pannus formation and that the increased expression of VLA-4, VLA-5, and ICAM-1 at the cartilage pannus junction may represent interaction with matrix protein. The VLA interaction appear to be involved in pannus attachment, whereas LFA-1 and ICAM-1 are involved in cell-cell interaction and may upregulate molecules such as VLA that are involved in attachment. | |
1509395 | [The use of radiothermometry in patients with rheumatoid arthritis]. | 1992 | As a result of the work carried out, one could decide some problems: to develop standardized points of measuring temperatures of the deep structures of the joints using radiothermography, to establish for the first time the normal radiothermographic values of the temperatures for different joint groups, to recommend radiothermography as an adjuvant method for revealing early signs of the activity of rheumatoid arthritis (RA) associated with OA. Radiothermography is a convenient, cheap, available and an informative enough method, fit for the use in clinical practice to improve the diagnosis and treatment of RA. | |
1326412 | The role of cytokines and their inhibitors in arthritis. | 1992 Jun | The role of cytokines in inflammatory joint diseases is well documented, especially with regard to tissue destruction and remodelling. In these processes, IL-1 and TNF alpha play a prominent part by stimulating protease production. The regulation of their production, their release and their effects on target cells (e.g. synovial cells, chondrocytes and bone-derived cells) has therefore been the subject of intensive investigations. In this context a new dimension has emerged recently due to the observation of the existence of natural specific cytokine inhibitors. IL-1-ra and the soluble fragments of both TNF receptors--inhibitory by binding to TNF alpha--are natural products. These appear to be the molecules best suited for controlling the imbalance between pro- and anti-inflammatory processes. The use of the recombinant forms of these inhibitors may open new perspectives for therapeutic intervention. The fact that the respective mechanisms of action of receptor antagonists and inhibitory binding proteins differ does not rule out their complementarity. Preliminary experiments with animal models have yielded promising results which should be followed up by clinical trials. | |
8356392 | Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthriti | 1993 | HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-classified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P < 0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course. |