Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2457376 | Synovial microenvironment-T cell interactions. Human T cells bind to fibroblast-like synov | 1988 Aug | Synovitis in rheumatoid arthritis is characterized by infiltration of the synovium by T and B lymphocytes and monocytes, as well as by the proliferation of synovial lining cells, fibroblasts, and endothelial cells. To study synovial cell-T cell interactions in vitro, we established cultures of fibroblast-like synovial cells, and used these cells in a synovial cell-T cell binding assay. Using T cells at various stages of differentiation and activation, we found that human thymocytes and mitogen-activated peripheral blood T cells bound to fibroblast-like synovial cells, whereas fresh peripheral blood T cells did not. Moreover, activated T cells from inflammatory synovial tissue or from synovial fluid also bound to fibroblast-like synovial cells cultured in vivo. Antibodies against certain epitopes of the T cell CD2 (35.1) and synovial cell lymphocyte function-associated antigen-3 (LFA-3) (TS2/9) molecules inhibited synovial cell-thymocyte binding. However, these same anti-CD2 and anti-LFA-3 antibodies only partially inhibited synovial cell binding to activated normal peripheral blood T cells. Moreover, T cells from inflammatory synovium from rheumatoid arthritis and psoriatic arthritis patients also bound to synovial cells in vitro. These findings demonstrate that fibroblast-like synovial cells are capable of binding to human T cells in vitro, and suggest that during the course of inflammatory synovitis, synovial fibroblast-T cell interactions may occur in vivo. | |
| 3207373 | Reaction of rheumatoid factors with IgG3 monoclonal anti-Rh(D) antibodies: more frequent r | 1988 Nov | Human monoclonal anti-Rh(D) antibodies of known IgG isotype and Gm allotype were bound to erythrocytes and then used as the target IgG antigens for rheumatoid factors (RFs) in a direct haemagglutination test. When serum samples from patients with rheumatoid arthritis (RA) were tested for RF specificity towards these IgG monoclonal anti-D antibodies the incidence and titre of reactivity towards an IgG3 monoclonal anti-D antibody was considerably greater than for a polyclonal anti-D antibody of the same Gm allotype, G3m(5). This difference was not explained by the amount of each anti-D antibody which bound to erythrocytes. Furthermore, when patients with RA were divided into groups according to their Gm phenotype, sera from a greater proportion of patients negative for the phenotype G3m(5) reacted to the G3m(5) monoclonal anti-D antibodies than sera from those patients positive for this allotype. Analysis of RF reactivities towards two IgG3 and three IgG1 monoclonal anti-D antibodies, each with different Gm allotypic epitopes, indicated, however, that individual serum samples contained RFs with a spectrum of specificities; some sera appeared to react to a single set of Gm alleles, whereas others also reacted to isotypic or iso-allotypic epitopes, or both. Our data suggest that RFs with specificity for Gm allotypes do not arise in patients who carry that particular allotype owing to tolerance induced in fetal-neonatal life. Conversely, RFs with apparent specificity for a Gm allotype formed in patients negative for that allotype may be reacting to a closely related but different epitope. Final proof requires precise specificities for each RF formed, and IgG3 monoclonal anti-D antibodies would be useful reagents for this purpose. | |
| 2625575 | [Radiographic study of bone resorption at the proximal end of the femur after total hip re | 1989 Dec | Radiography following cemented total hip replacement (THR) often revealed progressive bone resorption at the proximal end of the femur. The purpose of this study is to clarify the relation between this bone resorption and loosening of the acetabular component. The radiographic analysis was done using radiographs of two hundred and ninety-nine Müller type THR for osteoarthritis with minimum five years follow-up at regular intervals. The bone resorption at the proximal end of the femur appeared frequently in cases of loosened acetabular component. As acetabular loosening progressed, the bone resorption increased accordingly. Further study revealed that incidences of loosened acetabular component were statistically higher in cases of progressive bone resorption than in cases of non-progressive, 5.2 years after operation. This study indicates that progressive bone resorption might be a histological reaction caused by debris of pulverized bone cement generated by loosening acetabular component. The degree to which bone resorption progresses, therefore, directly reflects the amount of loosening of the acetabular component and should be a indicator for surgery to reconstruct loosened acetabular component. | |
| 2687142 | [Treatment of non-steroidal anti-inflammatory drug-induced damage to gastric mucosa using | 1989 Oct 30 | 339 patients with rheumatic diseases suffering from dyspepsia and endoscopically proven gastroduodenal lesion entered an open multicenter study with ranitidine 150 mg bid or ranitidine 300 mg administered at night in a single dose over 4 weeks. For entry the patients had to have been treated for at least 3 months with the non-steroidal anti-inflammatory drugs diclofenac, indomethacin and piroxicam. During the trial all patients were continued on NSAID. The data of 248 patients were evaluable. At entry, patients in both treatment groups had a total gastric damage score of 2.0. The duodenal lesion score was on average 1.43 in the ranitidine 150 mg bid group, and 1.8 in the 300 mg single dose ranitidine at night group. After 4 weeks of treatment the mean lesion score was significantly reduced in the stomach as well as in the duodenum with both ranitidine regimens, no differences being seen between the groups. In addition, rapid symptomatic relief was observed in both groups. After 4 weeks of treatment more than 80% of the patients were symptom-free or markedly improved. | |
| 2696861 | [Anticardiolipin antibodies in autoimmune rheumatic diseases]. | 1989 Jan | In this study, ELISA and VDRL tests have been employed in order to detect ACL antibodies in sera samples obtained from 105 patients with SLE, RA, scleroderma, dermatomyositis, primary Sjögren's syndrome, vasculitis and pulmonary thromboemboli; Using by IFAT, AMA-type 5 and other autoantibodies, RIA anti-DNA antibodies were also tested in SLE patients. In sera obtained from the patients with RA; autoantibodies and RF have been investigated. In SLE cases, ACL antibodies were found to be positive in 55.5% of the patients. In RA cases the rate of ACL antibodies were found to be 51.7%. In SLE cases, the presence of IgG-ACL antibody was found to be in association with thrombosis and fetal loss; while IgM-ACL antibody was found to be in association with fetal loss only. Serologic parameters such as VDRL and AMA type 5 were significantly connected with the presence of ACL-IgG and IgM antibodies (p less than 0.05). In cases of RA connection was detected only between IgG-ACL antibody and thrombosis. Concerning the other rheumatic autoimmune diseases; ACL antibodies were detected in cases: 4 patients out of 11 scleroderma, 1 patient out of 7 vasculitis, 2 patients out of 5 primary Sjögren's syndrome, and 3 patients out of 6 pulmonary thromboemboli. | |
| 1969728 | Can we develop simple response criteria for slow acting antirheumatic drugs? | 1990 Mar | The conventional assessment of response to slow acting antirheumatic drugs depends on multiple clinical and laboratory measures. Each measure is analysed separately. For clinical practice and therapeutic trials a single unified classification of response is preferable, based on the most sensitive and simple current measures. Whether or not this was practical was determined in a prospective study of two cohorts of patients: 145 given penicillamine 250-500 mg daily in a single dose; 98 sulphasalazine at an initial dose of 500 mg rising after one month to 2 g daily. Both groups were followed up for 12 months. A panel of 11 clinical and laboratory measures were evaluated every three to six months. Most changes had occurred by six months, and this was the optimum time to classify response. Four measures were used to devise a five point (0-4) classification of response from no change to remission. The objective was to evaluate if this approach is appropriate; the best level of each measure to use was not determined. The response index was based on: erythrocyte sedimentation rate less than 30 mm/h; articular index less than 3; morning stiffness less than 15 min; greater than 50% reduction in joint pain. Similar results were obtained with both drugs. The other clinical and laboratory measures gave limited information. This response index is simple and appropriate. It is suitable for use in clinical practice and drug studies, though the optimal values for dividing each clinical and laboratory variable need to be determined. | |
| 3639668 | Mini-plasminogen-like fragments of plasminogen in synovial fluid in acute inflammatory art | 1986 Aug 15 | Neutrophil elastase digests plasminogen to yield a fragment, mini-plasminogen, which is activatable to a mini-plasmin capable of escaping the action of the primary plasmin inhibitor. Such a molecule may play a role in joint destruction, either directly or by activation of procollagenase to collagenase. Synovial fluid samples from 34 acute joint effusions were examined by lysine-Sepharose chromatography and fibrinolytic assay of the fall-through (non-lysine-binding) fractions in presence of urokinase. Fragments similar to mini-plasminogen were found in 20 of 23 inflammatory effusions (cell count greater than 0.5 X 10(3)/microliter) and in none of 11 non-inflammatory (traumatic and osteoarthritic) effusions (cell count less than 0.5 X 10(3)/microliter) (p less than 0.001). Analysis of four inflammatory fluids by gel filtration on Bio-Gel P 100 and enzyme-linked immunoassay for plasminogen antigen revealed plasminogen fragments with molecular weight similar to mini-plasminogen (34,000 daltons) in three, and larger plasminogen fragments (or complexes of mini-plasminogen with other synovial fluid macromolecules) in all four. Fibrinolytic activity was demonstrable in fractions containing plasminogen fragments after treatment with tissue type plasminogen activator. In contrast with non-inflammatory effusions, inflammatory joint fluids contain plasminogen fragments with the properties of mini-plasminogen, suggesting their possible role in inflammatory joint destruction. | |
| 2218430 | IgG and IgA subclass distribution of total immunoglobulin and rheumatoid factors in rheuma | 1990 | The subclass distribution of IgG and IgA plasma cells, and in IgG and IgA rheumatoid factor (RF) producing cells was studied in sections of synovial tissue from seropositive RA and various types of seronegative arthritis, including ankylosing spondylitis, psoriatic arthritis, and Reiter's syndrome. The study was performed with immunofluorescence technique and monoclonal IgG and IgA subclass specific antibodies. IgG RF producing cells were identified by their ability to bind and activate factors both in the early (C3) and late (C5b-9) part of the complement cascade. IgA RF cells were identified by double staining experiments with heat-aggregated IgG and monoclonal antibodies to IgA subclasses. In 23 tissues tested for total IgG, IgG1 cells were usually predominant, while the frequency of IgG3 cells was usually higher than that of IgG2. In 19 tissues also tested for IgA, both IgA subclasses were present in all tissues. IgA1 plasma cells were always predominant, with a mean ratio of IgA1 to IgA2 cells of approximately 10. In the 13 tissues tested for RF-producing cells, the highest frequency of IgG RF cells was found among the IgG3 cells, followed by IgG1 and IgG2. IgA RF cells were found in only one case, all cells being IgA1. | |
| 1836395 | Interaction of recombinant monocyte-derived interleukin 1 receptor antagonist with rheumat | 1991 Sep | Interleukin 1 receptor antagonist (IL-1ra) is a newly described cytokine that is produced by human monocytes cultured on adherent immunoglobulin G (IgG). These studies have characterized the binding of IL-1ra to receptors on human rheumatoid synovial cells in comparison to binding of IL-1 alpha. The human synovial cells bound 35S-IL-1ra with a Kd of 213 pM and a Ki of 134 pM. 125I-IL-1 alpha bound to the synovial cells with similar values, showing a Kd of 205 pM and a Ki of 58 pM. Cross-inhibition studies were performed to examine whether IL-1ra and IL-1 alpha interacted with the same receptors and in an identical fashion. At the highest concentrations of inhibitory proteins, the binding of each ligand was inhibited 100% by the same or opposite ligand. This result indicated that IL-1ra and IL-1 alpha bound to the same receptors and not to overlapping subsets of receptors. In addition, the binding of 35S-IL-1ra was inhibited in an identical fashion by equimolar amounts of IL-1ra or IL-1 alpha. However, twofold or greater amounts of IL-1ra in comparison to IL-1 alpha were required to offer comparable inhibition of binding of 125I-IL-1 alpha. These results suggest that IL-1ra and IL-1 alpha bind with equal avidity to IL-1 receptors but may not bind identically. Additional experiments are necessary to establish whether these two ligands may bind to different regions of the extracellular portion of the IL-1 receptor. | |
| 2542542 | DNA synthesis in prolyl 4-hydroxylase positive fibroblasts in situ in synovial tissue. An | 1989 Mar | DNA synthesis in prolyl 4-hydroxylase (PH; EC 1.14.11.2) positive fibroblasts in situ in synovial tissue was studied using an autoradiography-avidin-biotin-peroxidase complex (ABC) double labeling. Fibroblasts in monolayer culture and in situ in synovial tissue were PH positive, whereas freshly isolated peripheral blood lymphocytes, monocytes, dendritic cells and granulocytes were PH negative. In rheumatoid arthritis (RA) 37 +/- 3 (22-56)% of all DNA synthesizing cells in situ were PH containing fibroblasts, whereas all DNA synthesizing cells in patients with meniscus lesion were PH positive. In both conditions, more than half of the self-replicating fibroblasts were located in the lining cell layer. This is probably not an artifact caused by insufficient penetration of 3H-thymidine because most of the DNA synthesizing lymphocytes were deep down in the synovial stroma. In RA 51 +/- 8 (17-88) PH positive fibroblasts in the S phase of the cell cycle were observed/3 mm2 synovial tissue, whereas the corresponding figure in meniscus patients was only 1 +/- 1 (0-5) (p less than 0.01). This suggests that the local fibroblasts in RA are activated, probably as a result of various fibroblast growth factors produced locally as a result of the inflammatory synovitis. In RA however, less than 1% of all local fibroblasts were self-replicating in situ, whereas labeling indices over 5% were not uncommon in RA synovial fibroblast cultures. This finding suggests that uncontrolled fibroblast proliferation is regulated in vivo by negative feedback mechanisms. | |
| 2054963 | Inhibition of elastase enzyme release from human polymorphonuclear leukocytes by N-acetyl- | 1991 Jan | We studied the effect of aminosugars on the elastase enzyme released from cytochalasin-B treated polymorphonuclear neutrophils (PMN) and stimulated by F-Met-Leu-Phe (FMLP). Both N-acetyl-galactosamine and N-acetyl-glucosamine can inhibit the release of leukocyte elastase enzyme. N-acetyl-galactosamine was a potent inhibitor of elastase enzyme release in a dose-related fashion. Inhibition ranged from 91.9% up to total inhibition. N-acetyl-glucosamine showed a mild inhibitory effect on elastase enzyme release; however, it too acted in a dose-related fashion. The range of inhibition was 17.17%-8.18%. Mannosamine showed an inhibitory effect in some donors, but this effect was not statistically significant. No effect on elastase enzyme release was shown with other sugars such as D-glucose and L-fucose. These results show that N-acetyl-galactosamine can inhibit the respiratory burst, which suggests that the aminosugars might do more than interfere with the carbohydrate lectin interaction. | |
| 1856805 | Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus. | 1991 Mar | We performed prospective hormonal studies in 9 patients (5 active and 4 inactive) with systemic lupus erythematosus (SLE) during pregnancy (Weeks 10 to 37). Nine healthy pregnant women and 5 patients with rheumatoid arthritis (RA) were used for comparison. Serum prolactin (PRL), testosterone and estradiol (E2) levels were determined by RIA. The patients with SLE showed higher serum PRL levels, the difference being statistically significant at Week 20, and reaching the highest levels at Weeks 30 to 40 (p = 0.05 when compared to healthy pregnant women). The 5 patients with active SLE had the highest serum PRL levels; one of these had fetal wastage. In active SLE the serum testosterone and E2 levels were decreased significantly from Weeks 10 to 30 compared with controls (p = 0.001). In patients with RA serum PRL levels, although higher than in controls, did not differ significantly, nor did the lower testosterone and E2 levels. We conclude that gonadal hormones and PRL changes observed in SLE are present also during pregnancy and may be related to fetal wastage and reactivation of disease. | |
| 2980129 | Function of the follicular dendritic cell in the germinal center of lymphoid follicles. | 1986 Oct | The authors made an immunocytochemical examination of the germinal centers (GCs) of (1) lymph follicles in physiological lymph nodes and (2) extra-nodal tissues of divergent diseases including thyroid disorders, rheumatoid arthritis, Warthin's tumor and Kimura's disease (Eosinophilic lymphfolliculoid granuloma). In these germinal centers, the presence of immunoglobulins (IgG and IgM), early acting complement components (C1q, C4, C3c, C3d), receptors for C3b and C3d and dendritic reticulum cell-1 was demonstrated in lace-like network patterns which were proven electron-microscopically to coincide with the surface of follicular dendritic cells. IgE was distributed in a lace-like pattern in the GCs of proliferating follicles of Kimura's disease, in which the lysis of follicles was frequently observed. This lysis appeared to be related to the presence of complement components. In the germinal centers of extra-nodal tissues, including the thyroid tissues accompanying the lymph follicles, rheumatoid arthritis synovial tissues as well as Warthin's tumors, thyroglobulin, rheumatoid factor and salivary amylase were detected as specific antigens, occurring in lace-like patterns. It is possible that follicular dendritic cells may play a role in the genesis of GCs and be responsible for the immune response through C3 receptors. | |
| 3382263 | Increased sensitivity of lymphocytes from patients with systemic autoimmune diseases to DN | 1988 Jun | Lymphocytes from patients with various diseases associated with autoimmunity showed both impaired capacity to repair O6-methylguanine (a powerful, promutagenic, directly miscoding base lesion) and increased sensitivity to the cytocidal effects of cellular methylation by N-methyl-N-nitrosourea (MNU) compared with normal controls and patients with other disorders. Defective repair of O6-methylguanine was significantly associated with arthritis and myositis in the group with systemic lupus erythematosus (SLE), and increased sensitivity to the toxic action of MNU was associated with the presence of immune complexes and the administration of steroids to patients with Behçet's syndrome. The results indicate that lymphocytes from patients with the autoimmune diseases studied are more susceptible to DNA damage with possible relevance to aetiopathogenesis. | |
| 2472146 | Cross-reactive antiidiotypic antibodies against human rheumatoid factors from patients wit | 1989 Jun | We prepared antiidiotypic (anti-Id) antibody to 2 polyclonal IgM rheumatoid factors (IgM-RF) and 2 polyclonal "hidden" IgM-RF. The anti-Id antibodies were isolated by chromatography on Sepharose 4B, to which was bound rabbit anti-human IgG Fc fragments. F(ab')2 fragments from the anti-Id antibodies were generated by pepsin digestion and isolated by gel filtration. The anti-Id antibodies directed against RF from 4 patients with juvenile rheumatoid arthritis (JRA) were tested by an inhibition hemolytic assay for cross-reactivity with IgM-RF from 4 adult patients with rheumatoid arthritis, 6 patients with JRA, and 13 JRA patients with hidden RF. The 4 anti-Id antibodies had variable cross-reactivity with the isolated adult RA RF, JRA RF, and JRA hidden RF. Similar results were obtained by a direct-binding enzyme-linked immunosorbent assay for the anti-Id antibodies. The broad pattern of cross-reactivity was apparently unrelated to a particular amino acid sequence, but was associated with the antigen-binding site of IgM-RF. These results suggest the possibility that the anti-Id antibodies prepared against isolated RF obtained from JRA patients bear the "internal image" of antigen; that is, the Fc region of human IgG. These anti-Id antibodies may be generated in JRA patients and may possess specific immunomodulatory properties. | |
| 1934688 | Human monocyte elastolytic activity, the propeptides of types I and III procollagen, prote | 1991 Jul | Elastolytic activity by live human monocytes (M phi) is mainly caused by cell surface related leucocyte elastase, capable of degrading matrix components. In order to examine the possible correlation between enzyme activity and tissue turnover in the joint, we examined 24 synovial fluids for M phi elastolytic activity, using the levels of synovial fluid interleukin-6 and serum C reactive protein as additional markers of cell activation. Proteoglycan levels were measured as an indication of cartilage degradation and the types I and III procollagen propeptides as markers of synovial membrane turnover. We found that elastolysis by live M phi and the levels of interleukin-6 and C reactive protein correlated significantly with proteoglycan concentrations but not with the procollagen propeptides. These findings suggest that human M phi elastolytic activation is a biologically relevant factor in cartilage degradation, but is unrelated to the collagen metabolism of the synovial membrane. | |
| 3689463 | Development of selective IgM deficiency in systemic lupus erythematosus patients with dise | 1987 Nov | Statistical analysis of serum immunoglobulin levels in 54 systemic lupus erythematosus (SLE) patients showed a decrease in serum IgM (normal 77 +/- 26 mg/dl; P less than 0.001) that was closely related to disease duration. The longer the duration of SLE, the more striking the decrease in serum levels of IgM (r = -0.74, P less than 0.01). Selective IgM deficiency (less than 47 mg/dl) occurred in SLE patients whose disease was clinically inactive or less active. | |
| 3495312 | A study of antipolynucleotide antibodies, anti-Klebsiella (K30) antibodies and anti-DNA an | 1987 Jun | Recent studies have indicated that both ankylosing spondylitis and the anti-DNA antibodies found in systemic lupus erythematosus may be related to Klebsiella surface antigens. In order to explore these possible relationships further, the sera of 24 patients with ankylosing spondylitis (AS), and 20 controls, have been examined for binding to a wide range of antipolynucleotide antibodies, antibodies binding to the Klebsiella pneumoniae polysaccharide K30 and two DNA antibody idiotypes designated 16/6 and 134. We report that although 21% of the AS patients had IgG ssDNA antibodies it is evident that the aetiopathogenesis of this disease is not through the mechanism of autoantibodies or the common DNA antibody idiotypes tested. | |
| 3070722 | Quantitation of rheumatoid factors (RF) of IgM, IgA and IgG isotypes by a simple and sensi | 1988 | An enzyme-linked immuno-sorbent assay (ELISA) for quantitation of rheumatoid factors (RF) of IgM, IgA and IgG isotypes has been established. A complex of human serum albumin (HSA) and rabbit IgG anti-HSA antibodies is used as antigen for RF. The binding of RF is detected by stepwise additions of biotinylated monoclonal antibodies specific for human IgM, IgG or IgA, alkaline phosphatase-conjugated streptavidin, and substrate. The assay is simple and applicable to routine testing of large numbers of sera. It discriminates between false and true IgG-RF by papain digestion of sera that turn out positive by the screening for IgG-RF. Of 241 randomly selected patients with rheumatoid arthritis (RA) as well as other rheumatoid and infectious diseases, 110 were Waaler-Rose-positive while 127 were IgM-RF-positive in ELISA. The correlation between the Waaler-Rose test and IgM-RF ELISA was highly significant (r = 0.82). By testing 65 of these sera (all IgM-RF positive), 25 (39%) were also true IgG-RF positive (42 (64%) in the screening). When 40 Waaler-Rose-positive RA patients were tested, 20 and 21 were also positive for IgG- and IgA-RF, respectively. Eight IgM-, one IgA- and no IgG-RF positive tests were recovered when 48 Waaler-Rose negative RA patients were studied. | |
| 1841047 | The effect of slow-acting anti-rheumatic drugs (SAARDs) and combinations of SAARDs on mono | 1991 | The mode of action of slow-acting anti-rheumatic drugs (SAARDs) is complex but may often include effects on cytokine (interleukin-1, IL-1, and tumour necrosis factor, TNF) production by monocytes/macrophages. Different SAARDs may have variable effects on cytokine production in vitro depending on the concentration of drug, the presence of other SAARDs and individual variation. The gold compounds gold sodium thiomalate (GST) and auranofin (AF) had a bimodal effect on cytokine production. High concentrations of GST (greater than 1 microgram/ml) weakly inhibited IL-1-beta secretion (without affecting IL-1-alpha or TNF secretion and without affecting cell-associated IL-1-alpha and IL-1-beta accumulation), and although AF (greater than 100 ng/ml) inhibited cytokine production it did so at concentrations near to the toxic range for the drug (greater than 200 ng/ml). GST and AF when used in combination inhibited cytokine production in a synergistic manner even at concentrations that would potentiate cytokine production if used individually. Hydroxychloroquine (HCQ) and sulfasalazine (SAP) were two other inhibitory SAARDs which acted synergistically in combination. Combination of HCQ and SAP with gold drugs gave variable results. D-penicillamine (D-pen) and methotrexate (MTX) were two SAARDs that generally did not affect cytokine production individually or in combination with other SAARDs. These results suggest that combination SAARD therapy may more effectively target excessive cytokine production, which is a hallmark of rheumatoid arthritis. |