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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8139127 | [Detection of antineutrophil cytoplasmic antibodies in sera from patients with rheumatoid | 1994 Feb | Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from 52 patients with rheumatoid arthritis (RA), including 9 patients with malignant RA (MRA) and 20 healthy controls were examined by indirect immunofluorescence technique (IIF). Nine out of 52 RA patients showed positive ANCA staining. None of MRA patients had, however, ANCA in sera. The staining pattern for ANCA was either perinuclear for 4 sera or non-specific for 5 sera, but not cytoplasmic. Furthermore, anti-nuclear antibodies (ANA) in 9 ANCA positive RA sera were tested by IIF, using Hep-2 cells. Six sera had positive ANA. Three sera showed as nucleolar and 1 serum as centromere in ANA staining pattern. The incidence of these ANA staining pattern in ANCA positive sera (4 out of 9) was higher than in ANCA negative sera (1 out of 19). The clinical profiles and laboratory findings of 9 RA patients with positive ANCA revealed that they had suffered and treated for more than 10 years and had still active joint inflammation, like intractable RA. These results indicate that ANCA in RA are not associated with vasculitis. | |
7932407 | Increase in adhesion molecules on CD4+ cells and CD4+ cell subsets in synovial fluid from | 1994 Jun | OBJECTIVE: To elucidate the role of adhesion molecules in the pathogenesis of rheumatoid arthritis (RA). METHODS: We evaluated their expression and that of an activation marker on CD4+ cell populations and CD4+ cell subsets in specimens of peripheral blood (PB) and synovial fluid (SF) obtained from 10 patients with RA and 7 with osteoarthritis (OA). A 2 or 3-color immunofluorescent method was used for analysis. RESULTS: The SF from both groups of patients showed a greater density of adhesion molecules including LFA-1 alpha, LFA-1 beta, CD2, VLA-4 alpha and VLA-5 alpha on CD4+ cells, and a higher percentage of CD4+HLA-DR+ cells compared with their PB. IN PB-CD4+ cell subsets from the arthritic and healthy subjects, the CD4+CD45RO+ cell population showed an increased expression of adhesion molecules compared with CD4+CD45RA+ cell population. The expression of adhesion molecules on circulating CD4+ cell population and CD4+ cell subsets from the patients with RA and OA was comparable to that from healthy subjects. SF from both groups of patients showed a higher percentage of CD4+CD45RO+ cells and a lower percentage of CD4+CD45RA+ cells. In SF-CD4+ cell subsets from patients with RA, the CD4+CD45RO+ cell population had an increased expression of VLA-4 alpha compared to the CD4+CD45RA+ cell population; however, there was no significant difference in other adhesion molecule expression and the percentage of HLA-DR+ cells between the 2 cell subsets. Furthermore, the expression of VLA-4 alpha on the CD4+CD45RO+ cell population in SF from patients with RA was significantly higher than that in matched PB. In CD4+CD45RA+ cell population from both groups of patients, SF showed an enhanced expression of adhesion molecules and an increased percentage of HLA-DR+ cells compared with matched PB. CONCLUSION: Our results suggest that increased expression of adhesion molecules and increased percentage of HLA-DR+ cells on CD4+ cells in SF may be responsible for cellular interactions between these cells and synovial cells or extracellular matrix. | |
1411797 | [Improvement of pancytopenia and articular and by splenectomy in a patient with Felty's sy | 1992 Aug | A forty seven year-old woman with a 18 years history of rheumatoid arthritis presented with recurrent infection and pancytopenia. A diagnosis of Felty's syndrome was made hand on clinical and laboratory findings. In spite of drug therapy using nonsteroidal anti-inflammatory drugs, D-penicillamine and corticosteroid, the hematological abnormalities and active joint symptoms continued. Recurrences of severe bacterial infection and the rupture of esophageal varices necessitated splenectomy. Soon after the operation, dramatic improvement of hematological abnormalities were observed. Furthermore, after 3 months postoperatively, marked decrease in rheumatoid activities and disappearance of subcutaneous nodules were noticed. Titer of rheumatoid factor also showed a significant reduction and became negative 6 months after the operation. Although the efficacy of splenectomy on hematological abnormalities in Felty's syndrome has been well documented, its effect on rheumatic disease has not been clarified. The case presented here might suggested that suppression of reticuloendothelial system may have therapeutic effects in rheumatoid arthritis. The possible mechanisms involved in these findings have been discussed. | |
7552062 | Genes and arthritis. | 1995 Apr | Familial clustering is a common feature of many different arthritic conditions which can be explained by shared genetic or environmental influences or a combination of these. The aetiology of some of these diseases (e.g. multiple epiphyseal dysplasia, Lesch-Nyan syndrome) is clearly monogenic but the majority of common rheumatic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA) are complex and multi-factorial with a polygenic component. In the last 10 years there has been spectacular progress in unravelling the underlying genetic mechanisms of many monogenic disorders including many that affect the musculoskeletal system. Among these osteogenesis imperfecta (OI) and the Marfan syndrome are striking examples in which molecular defects of matrix protein components of the mesodermal tissues have been revealed. In particular, the power of modern molecular genetics both to test candidate genes (e.g. collagen in OI) and to identify genes where no prior knowledge of the protein defects exists (e.g. fibrillin in the Marfan syndrome) has proved quite remarkable. In the near future many of the techniques that have been applied successfully to these monogenic diseases can be expected to provide insights into the genetic component of common diseases, such as rheumatoid arthritis. However, it is important to realize before embarking on these studies that even monogenic diseases may provide significant problems of analysis and interpretation. Some of these problems are exemplified below (e.g. phenocopies, mosaicism, imprinting). | |
8895144 | Mobilization of fibrinolytic enzymes in synovial fluid and plasma of rheumatoid arthritis | 1996 Oct | OBJECTIVE: To study the role of fibrinolytic enzymes in inflammatory joint diseases with different types of joint destruction. METHODS: Concentrations of the plasminogen activators pro-urokinase, tissue plasminogen activator, plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), plasminogen, and fibrin split product D-dimer in synovial fluid (SF) and blood plasma of 29 patients with rheumatoid arthritis (RA) were compared with the concentrations of 18 patients with spondyloarthropathy (SpA). Levels of the fibrinolytic components were also related to radiological destruction assessed using the Larsen grading system. RESULTS: Patients with RA had significantly higher PAI-1 antigen levels and PAI-1 activity in SF than patients with SpA. Plasma levels of PAI-1 antigen and D-dimer were significantly higher in RA than in SpA. There was also a tendency of lower tPA activities in SF and plasma of patients with RA. Joint destruction correlated significantly with increasing PAI-1 antigen and with decreasing plasminogen in SF when results from all patients were pooled. A significant negative correlation between plasma PAI-2 antigen and Larsen grade was also found. CONCLUSION: Our results indicate a possible association between joint destruction and mobilization of fibrinolytic enzymes in SF. | |
8250989 | The effect of long-term methotrexate therapy on hepatic fibrosis in rheumatoid arthritis. | 1993 Dec | OBJECTIVE: To evaluate the progression of hepatic fibrosis in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX). METHODS: Fifteen patients receiving MTX for RA were prospectively studied by electron microscopic analysis of biopsy specimens. RESULTS: Five of the 15 patients had evidence of increased hepatic collagen after 2 years of MTX therapy. CONCLUSION: Hepatic fibrosis may progress in a subgroup of RA patients treated with MTX. | |
1540664 | Cytotoxic effects of rheumatoid arthritis sera on chondrocytes. | 1992 Feb 14 | Human sera from patients with rheumatoid arthritis (RA) and also from healthy donors were found to be toxic to cultured chondrocytes. Immunoglobulins were found to bind to the surface of cultured cells and cells in chicken sternal cartilage, as detected by indirect immunofluorescence. In vitro, cell detachment from the substrate was caused by the incubation of chondrocyte monolayers with 5 per cent and less RA serum. Serum treatment caused cytotoxic degradation of the cells. This could be quantified by a chromium release assay. Heat inactivation of the serum abolished the cytotoxicity. The extent of the cytotoxic reaction was related to the complement content of the serum and also to the intensity of the disease, as determined by the Ritchie-index. Other cell types, as chondrosarcoma cells, normal fibroblasts and corneal epithelium, were not affected by RA sera. | |
8429406 | Hormones, cytokines and body composition: can lessons from illness be applied to aging? | 1993 Feb | Loss of lean body mass (LBM) is a hallmark of aging and of acute and chronic illness. Loss of more than 40% of lean mass is not compatible with life. The causes of loss of LBM in aging remain obscure, although changes in growth hormone production, physical activity and the cytokines interleukin-1 beta and tumor necrosis factor-alpha may play a role. The usefulness of a disease model based on rheumatoid arthritis (RA) is considered, in which all these changes occur to a greater degree and independently of age. RA is a common autoimmune condition in which cytokine production is increased, LBM is reduced and mortality is greatly accelerated. These observations suggest that, with respect to body composition at least, RA represents a model of "accelerated" aging. A hypothesis is presented that unifies metabolic and immunologic observations and changes in body composition. The interrelationship of the immune system and body composition is an important area that deserves further investigation. | |
1535493 | Predictors of disability in a longitudinal sample of patients with rheumatoid arthritis. | 1992 May | Information from the Health Assessment Questionnaire (HAQ) is used to identify which variables measured in 1981 successfully predict the severity of disease in 1989 and the eight year change in severity of disease in a sample of 330 residents of Santa Clara County, California, USA. This study is exploratory and no previous hypotheses are made. Using univariate correlations and stepwise linear regressions, initial values of a number of variables are found to be useful predictors including, in order: the HAQ disability index, pain scale, global health status, tender joints, few work hours, age, female sex, never married, widowhood, and occupation as operative (e.g. dry wall installers, assemblers). Data suggest that deterioration over eight years is least rapid for those with severe disease in 1981. A mathematical identity suggests that analyses of the changes in severity versus analyses of 1989 severity are identical, provided that the 1981 disability index is entered as a covariate. The initial level of the disability index of the HAQ is by far the strongest predictive variable and provides a clinically important gauge for the likelihood of future impairment. | |
1555336 | The Kessel prosthesis in total shoulder arthroplasty. A five-year experience. | 1992 Apr | Between 1982 and 1985, 23 Kessel total shoulder arthroplasties were performed on 22 patients. A clinical and roentgenographic review was performed by an independent observer. Three patients had their prostheses removed and three had revision surgery, leaving 17 shoulders in 16 patients available for study, all with rheumatoid arthritis (RA). All patients were relieved of pain and noticed a general improvement in activities of daily living. Passive flexion and rotation were increased, but active movements remained unchanged. Roentgenographically, radiolucent zones developed around the scapular component on all patients within one year but only around one of the humeral components. Total shoulder arthroplasties with the Kessel prosthesis in RA relieved pain and improved shoulder and arm function. The long-term results were complicated by a high incidence of loosening of the glenoid component, probably a feature of the constrained design of the Kessel prosthesis. | |
8548200 | The number of glucocorticoid receptors in peripheral human lymphocytes is elevated by a zi | 1995 | A trace element preparation (Béres Drops Plus, BDP) elevates the number of glucocorticoid receptors (gcR) in peripheral lymphocytes isolated both from healthy blood donors and rheumatoid arthritis patients. This enhancement by BDP was found either for constitutive expression of gcRs or in experiments when the lymphocytes were stimulated by interleukin (IL)-6. There was no significant effect of BDP on IL-1 and tumour necrosis factor alpha (TNF alpha)-induced changes of gcRs. The effect of BDP was greatly dependent on the presence of Zn++ ions in the preparation, since the augmenting effect was abolished if BDP did not contain zinc. | |
8241593 | Increased RAHA titer and interleukin-6 levels in the synovial fluid in a patient with poly | 1993 Jun | We report a patient with polymyalgia rheumatica (PMR) accompanied by an increased Rheumatoid Arthritis Hemagglutinin Test (RAHA) titer and interleukin-6 level in the synovial fluid. A 60-year-old female was admitted because of polymyalgia, a body temperature of 39.2 degrees C, and an erythrocyte sedimentation rate increased to 94 mm/h. Since a muscle biopsy failed to show a specific finding, she was diagnosed as PMR. The titer of RAHA and the interleukin-6 level were increased only in the synovial fluid; prednisolone treatment decreased both. The present case raised the possibility that a similar mechanism in rheumatoid arthritis may involve the development of synovitis in PMR. | |
8976639 | Staphylococcus aureus nasal carriage in rheumatoid arthritis: antibody response to toxic s | 1996 Nov | OBJECTIVE: To determine the prevalence of Staphylococcus aureus nasal carriage and to compare antibody responses to two superantigens, staphylococcal toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA), in rheumatoid arthritis patients and normal subjects. METHODS: 88 rheumatoid arthritis patients and 110 control subjects were cultured for nasal carriage of S aureus; 62 isolates were bacteriophage typed. Twenty five patients and 11 spouses were tested for antibodies to TSST-1, SEA, and sonicate extracts of Bacteroides fragilis and Escherichia coli; 19 patients were HLA-DR typed. RESULTS: 50% of patients and 33% of normal subjects were S aureus carriers. Bacteriophage typing of isolates suggested significant differences between strains isolated from the two groups. Patients showed higher IgG (P = 0.0025) and IgA (P = 0.0372) antibody levels to TSST-1 than normal spouses and these responses were not related to rheumatoid factor titres or HLA-DR type. CONCLUSION: When compared to normals, rheumatoid arthritis patients more often carry S aureus in their nasal vestibule, carry a distinct subpopulation of S aureus strains, and have higher average antibody levels to TSST-1. | |
1373345 | The search for laboratory measures of outcome in rheumatoid arthritis. | 1992 Feb | A large number of laboratory tests have been developed within the past decade to measure factors involved in the immune inflammation of RA. These can be divided into genetic markers, general measures of inflammation, autoantibodies and tissue-specific markers. In general, it is simpler to prove the power of a certain test to measure the disease process than to predict outcome. Apart from RF positivity and CRP/ESR, few, if any, tests have proven to be of importance in independent studies from different centres. Among the promising candidates for future work are detailed analysis of the HLA-D region genes, sulphoxidation status, the autoantibody against RA33 nuclear antigen, soluble IL-2 receptor measuring lymphocyte activity, hyaluronate/hyaluronan or PIIINP from synovial tissue, the combined use of COMP and proteoglycan epitope tests for cartilage matrix, and pyrodinoline cross-linking for collagen from bone and cartilage. The ideal setting for testing such markers are prospective cohort studies starting early in the disease, and since many such studies have been initiated recently, one can expect much new information in coming years. Attention needs to be devoted to the kinetics of marker metabolism, since many are degraded or removed at very fast rates from the circulation, making serum assays less informative. | |
7818570 | Modified disease activity scores that include twenty-eight-joint counts. Development and v | 1995 Jan | OBJECTIVE: The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts. METHODS: These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated. RESULTS: No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists). CONCLUSION: The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts. | |
1293587 | [The role of iron in immunologic processes]. | 1992 | Iron, apart a for long time well-known function connected with: transportation (hemoglobin), storage (myoglobin), and utilize (cytochromes, cytochrome oxidase) oxygen for respiration, has a critical role in host-pathogen interactions. Iron is essential for microbial growth, but also for immune function. The role of iron in infection, thermoregulation, acute lymphocytic leukemia, neoplasia, rheumatoid arthritis, stimulation of free radical reactions, and studies with iron chelation therapy are discussed. | |
9061381 | Increase in the expression of alpha E beta 7, characteristic of intestinal intraepithelial | 1996 | The intestinal epithelium contains a distinct group of lymphocytes (iIEL). The majority of iIEL are T cells characterized by a phenotype different from PBL. This phenotypic peculiarity has led to the hypothesis that iIEL, develop in a thymus-independent fashion, that they may develop locally in the gut epithelium itself and that they have the distinct function of providing a first line of defense in the gut. We looked at the expression of the gut-associated surface molecule alpha E beta 7 on T cells in inflamed tissues outside the gut epithelium. The already high frequency of 41.8% alpha E beta 7+ T cells in bronchoalveolar lavage from healthy lungs rises to a median of 61% in a fibrotic lung. In synovial fluid the percentage of T cells expressing alpha E beta 7 was diverse; it was not as high as in the lung but was elevated compared to PBL levels. In both tissues, the increase in alpha E beta 7 expression correlated with an increase in CD8+ cells. We discuss our data in the context of a model in which iIEL can leave the gut epithelium and become involved in inflammatory processes, possibly related to autoimmune disease. | |
8586087 | Imaging of pulmonary disease in rheumatoid arthritis using J001X scintigraphy: preliminary | 1995 Dec | The purpose of this study was to determine the ability of technetium-99m J001X scintigraphy to image active pulmonary involvement in patients suffering from rheumatoid arthritis (RA). J001X is a fully characterized acylated poly(1,3)galactoside, isolated from Klebsiella membranes, which is able to bind recruited macrophages after aerosol administration. J001X scintigraphy was compared with high-resolution computed tomography (HRCT), pulmonary function tests (PFTs) and bronchoalveolar lavage (BAL) in 15 patients suffering from RA. Patients were considered to have pulmonary involvement when they had an interstitial syndrome on HRCT and a decrease of 20% in TCO/VE (transfer coefficient) on PFTs and/or an abnormal BAL (lymphocytosis higher than 20% and/or percentage of neutrophils higher than 10%). Pulmonary involvement was present in eight patients, and absent in seven. Of the eight patients with pulmonary involvement, all had abnormal BAL, two had an interstitial syndrome on HRCT, two had decreased TCO/VE and three had positive J001X scintigraphy. Of the seven patients without pulmonary involvement, six had normal BAL (not available in one), two had an interstitial syndrome on HRCT, one had decreased TCO/VE and two had positive J001X scintigraphy. According to our gold standard of pulmonary involvement, the sensitivity of J001X scintigraphy for the detection of pulmonary involvement in RA was 37.5%, the specificity was 71.4% and the positive predictive value was 60%. The ability of J001X scintigraphy to detect active pulmonary involvement during RA appears unclear in this study but it may detect processes unnoticed by the other modalities. These patients will be followed 12 and 24 months later and the changes in J001X scintigraphy, HRCT and PFTs will be compared to demonstrate whether J001X scintigraphy is able to assess an active process in the pulmonary involvement during RA and to specify its predictive value. | |
7789064 | Campylobacter jejuni arthritis in secondary amyloidosis. | 1995 Mar | We describe a case of infectious arthritis caused by C. jejuni which developed after C. jejuni enteritis in a patient with rheumatoid arthritis and hypogammaglobulinaemia. Extraintestinal infections of this enteropathogen are rare, but in patients with hypogammaglobulinaemia C. jejuni bacteriaemia is relatively common. The present patient suffered from hypogammaglobulinaemia due to a nephrotic syndrome in secondary amyloidosis. C. jejuni infection must be considered in patients with hypogammaglobulinaemia and arthritis. | |
8895536 | Overall cancer incidence not increased after prosthetic knee replacement: 14,551 patients | 1996 Sep 27 | It is unknown whether patients as a consequence of prosthetic joint replacement are at a higher risk of developing cancer. We therefore analyzed cancer incidence following prosthetic knee replacement (TKR). The observed cancer incidence in 14,551 patients from the population-based Swedish Knee Arthroplasty Register who have undergone TKR because of osteoarthrosis (OA, n = 10,120) or rheumatoid arthritis (RA, n = 4431) were compared with the expected cancer incidence for a Swedish reference population. The cohort was followed for a total of 66,622 person-years. We followed 33% of the patients with OA and 59% of those with RA for more than 5 years. All patients who underwent TKR, whether for OA or for RA, had lower than expected total cancer incidence. We found a markedly low incidence of colorectal carcinoma, especially in patients with RA. Our results do not indicate an increased incidence of cancer following TKR. |