Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2805610 | Iron-binding proteins and free iron in synovial fluids of rheumatoid arthritis patients. | 1989 Sep | Iron-binding proteins (lactoferrin, transferrin and ferritin) and free iron were measured in synovial fluid (SF) from 30 patients with rheumatoid arthritis (RA) and 20 osteoarthritis (OA) patients. The iron-binding proteins except transferrin were significantly increased in RA SF as compared with OA SF. Similarly, free iron was also significantly higher in RA SF than in OA SF, whereas the ferritin saturation index, transferrin saturation index and bound iron were more significantly decreased in RA SF than in OA SF. These results suggest that RA SF contains sufficient micromolar amounts of free iron to allow hydroxyl radical formation. Also the capacity of iron-binding proteins to bind free iron is inadequate in the presence of a large amount of iron-binding proteins which are present in RA SF. | |
| 2666652 | Presence of platelet glycoproteins Ib and IIb-IIIa in inflammatory and noninflammatory syn | 1989 May | Rheumatoid synovial tissue and noninflammatory synovial tissue from patients with meniscus lesions were stained using monoclonal antibodies against platelet 150 kDa Ib glycoprotein (gp Ib) and against 140/110 kDa IIb-IIIa glycoprotein complex (gp IIb-IIIa) applied with the avidin-biotin-peroxidase complex method. Gp Ib and gp IIb-IIIa positive intravascular platelet aggregates were not seen, except locally in the capillary blood vessels of one rheumatoid synovial sample. This suggests that the platelets and the clotting sequence are not activated in inflamed synovial tissue. However, in many of the synovial capillaries endothelial immunoreactivity was seen. This reaction could have been due to cross reaction, since the vitronectin receptor beta chain is structurally identical to platelet gp IIIa. The gp IIb-IIIa member of the integrin receptor family plays a role in the transmembrane linkage between its extracellular ligands and intracellular microfibers. Gp IIb-IIIa may thus contribute to normal synovial physiology and to the pathogenesis of chronic synovitis. | |
| 3794338 | Gender differences in eicosanoid production from macrophages of arthritis-susceptible mice | 1987 Jan 15 | Collagen-induced arthritis (CIA) in rodents is an experimental animal model that shares many clinical and pathologic findings with rheumatoid arthritis in man. Our previous findings suggested that the amelioration of CIA in mice by a fish oil diet was associated with macrophage accumulation and metabolism of eicosapentaenoic acid and a subsequently altered prostaglandin (PG) profile. In these experiments, we examined the role of gender and found that macrophages from female arthritis-susceptible B10.RIII or B10.G mice synthesized more PG and thromboxane than macrophages isolated from the males. Compared with males, female mice had higher circulating anti-type II collagen antibodies but were less likely to develop CIA. Females, especially those on a fish oil diet, developed a much less severe disease than the males. This supports our hypothesis that the type and/or amount of eicosanoid produced from the macrophage may alter the course of experimentally induced arthritis. | |
| 3818949 | Monomeric (7S) IgM found in the serum of rheumatoid arthritis patients share idiotypes wit | 1987 Mar | Serum from some seropositive (RF+) rheumatoid arthritis (RA) patients contains relatively high concentrations of monomeric (7S) IgM molecules. Seven S IgM molecules fail to bind the Fc portion of IgG, unlike 19S IgM RFs that bind aggregated IgG in classical RF assays. Some pentameric IgM RFs are marked by crossreactive idiotypes (RCRI) defined by prototypic monoclonal RFs. In previous studies, we observed that a proportion of pokeweed mitogen (PWM) induced plasma cells from RA patients' blood lymphocytes express the major RCRI as assayed by indirect immunofluorescence with polyclonal anti-RCRI antibodies. In this study, 7S IgM obtained from three different RF+ RA patients inhibits specific anti-RCRI intracytoplasmic staining of PWM induced RF+ RA-derived plasma cells. These 7S molecules also block polyclonal anti-RCRI antibodies from reacting with red blood cells bearing 7S IgM molecules from RF+ patients with RA or Waldenstrom's macroglobulinemia. We conclude that some 7S IgM molecules in the serum of RF+ RA patients are marked by the major RCRI idiotype and are related to 19S monoclonal and polyclonal RFs. | |
| 1976811 | Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospe | 1990 Aug | During a continuous 14-year observation period we prospectively recorded clinical data on all patients with rheumatoid arthritis (RA) attending an outpatient clinic. Six hundred seventy-one patients received 1017 new administrations of slow acting antirheumatic drugs during more than 2000 patient years of observation. The median time to discontinuation for intramuscular gold, auranofin, hydroxychloroquine or penicillamine was 2 years or less, but was 4.25 years for methotrexate (p = 0.008 vs all other drugs combined). Adverse reactions were a more common reason for discontinuation than efficacy, and both were less common in patients taking methotrexate (p less than 0.01). Neither disease duration, disease severity, or demographic factors were useful predictors of discontinuation. Since controlled clinical trials do not provide long-term outcome assessments, measurement of time to termination is a practical tool to estimate drug inefficacy. | |
| 1658811 | Reactive oxygen species, lipid peroxides and essential fatty acids in patients with rheuma | 1991 Aug | We studied free radical generation, lipid peroxidation and the levels of essential fatty acids and of their metabolites in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Both superoxide and hydrogen peroxide generation by peripheral leukocytes but not malondialdehyde levels, as measured by thiobarbituric acid assay, were found to be significantly enhanced both in RA and SLE. Fatty acid analysis of the plasma PL fraction revealed that both LA and ALA metabolites are significantly decreased in RA and SLE compared to controls. These results suggest that essential fatty acid metabolism is altered in RA and SLE. | |
| 2433075 | Salivary amylase and pancreatic enzymes in Sjögren's syndrome. | 1987 Feb | Concentrations of immunoreactive trypsin (IRT) and pancreatic and salivary amylase activities were measured in 22 patients with primary Sjögren's syndrome (SS) and in 13 patients with secondary SS. Nineteen of the 22 patients with primary SS had above-normal IRT, and six had above-normal pancreatic isoamylase activity. Six of the 13 patients with secondary SS had above-normal IRT; none had above-normal isoamylase activities. Serum IRT and pancreatic isoamylase were correlated significantly (r = 0.7; p less than 0.0001). Above-normal values for IRT and pancreatic isoamylase were more frequent in patients who had SS for longer than 10 years, but were not related to the presence of salivary gland autoantibodies or to salivary isoamylase activity. We conclude that the concentration and activity of pancreatic enzymes are frequently abnormal in SS; that the abnormality is greater and more frequent in patients with primary SS; and that it increases with the duration of the disease. | |
| 3687583 | Drug effects on a novel model of connective tissue breakdown. | 1987 Aug | Production of a granulomatous tissue adjacent to cartilage implants in subcutaneous tissues of mice by prior wrapping of cartilage with cotton, induces matrix depletion and a rise in serum levels of the acute phase protein haptoglobin. The granulomatous reaction to cotton could be inhibited partially, following treatment of mice with indomethacin, dexamethasone and cyclophosphamide but only the latter two reduced cartilage matrix loss. D-penicillamine was inactive. Regarding the acute phase response, dexamethasone and D-penicillamine appeared to lower and indomethacin and cyclophosphamide to elevate, serum levels of haptoglobin, but these effects were not statistically significant. | |
| 2963340 | Clonal dominance among T-lymphocyte infiltrates in arthritis. | 1988 Feb | Synovial membranes in patients with rheumatoid arthritis as well as other types of chronic destructive inflammatory arthritis contain infiltrates of activated T lymphocytes that probably contribute to the pathogenesis of the disease. In an effort to elucidate the nature of these infiltrates, interleukin 2 (IL-2)-responsive T lymphocytes were grown out of synovial fragments from 14 patients undergoing surgery for advanced destructive inflammatory joint disease. Eleven of the samples examined were from patients with classical rheumatoid arthritis, while three others were obtained from individuals with clinical osteoarthritis. Southern blot analysis of T-cell receptor (TCR) beta-chain genes in 13 of 14 cultures showed distinct rearrangements, indicating that each culture was characterized by the predominance of a limited number of clones. T-cell populations from peripheral blood stimulated with a variety of activators and expanded with IL-2 did not demonstrate evidence of similar clonality in long-term culture. These results suggest that a limited number of activated T-cell clones predominate at the site of tissue injury in rheumatoid synovial membranes as well as in other types of destructive inflammatory joint disease. Further characterization of these T-cell clones may aid our understanding of the pathogenesis of these rheumatic disorders. | |
| 3731210 | Tolerability and efficacy of long-term daily administration of indomethacin for moderate t | 1986 | The long-term tolerability and efficacy of indomethacin were evaluated in a retrospective study of 67 patients with moderate to severe rheumatoid arthritis, osteoarthritis, or ankylosing spondylitis who took the drug daily for periods ranging from three to 20 years. Only patients who had not experienced side effects during the first ten to 14 days of indomethacin therapy were included. No other anti-inflammatory agents were taken along with indomethacin. The average daily dosage ranged from 50 to 150 mg; for 81% of patients, the average daily dosage was 75 to 100 mg. Only nine (13%) of the 67 patients experienced side effects, all of which were transient and mild. Three patients had headache, five patients had gastrointestinal symptoms, and one patient had both gastrointestinal symptoms and headache. Repeated urinalyses did not reveal any significant abnormalities. There were no instances of leukopenia. A comparison of clinical and laboratory assessments at the initial and latest office visits indicated that signs of active inflammation had been well controlled by daily indomethacin therapy. Erythrocyte sedimentation rates were generally lower and hemoglobin values tended to be higher at the latest visit. Clinically, patients appeared to have benefited from the long-term administration of indomethacin with respect to both tolerability and efficacy. | |
| 2042981 | Uptake and degradation of soluble aggregates of IgG by monocytes of patients with rheumato | 1991 May | Monocytes from patients with rheumatoid arthritis (RA) and rheumatoid vasculitis have a diminished ability to degrade soluble complexes of aggregated IgG in the absence (mediated by Fc receptors) as well as in the presence of complement (C) (mediated by (Fc + C) receptors). To investigate whether a relation exists between the receptor mediated degradation of aggregated IgG by adherent monocytes and disease activity a longitudinal study was performed in 79 patients with RA and rheumatoid vasculitis over a period of 16 months. Adherent monocytes were incubated in vitro with 125I labelled IgG aggregates of restricted size in the absence or presence of fresh serum and the percentage of catabolised IgG aggregates was measured. Cross sectionally the degradation of aggregated IgG by monocytes, mediated by Fc and (Fc + C) receptors, correlated significantly with disease activity as scored by the Ritchie articular index, the presence of extra-articular features, and circulating immune complexes. A high number of Fc receptors on monocytes correlated with diminished degradation, whereas high numbers of complement receptors 1 and 3 correlated with enhanced degradation of aggregated IgG mediated by both Fc and (Fc + C) receptors. The degradation of aggregated IgG by monocytes did not correlate with disease activity in individual patients followed up longitudinally. When patient groups were formed according to the results of longitudinal studies, however, degradation of aggregated IgG mediated by Fc and (Fc + C) receptors was significantly decreased in patients with rheumatoid vasculitis and in patients with active RA in comparison with patients with inactive RA and healthy controls. Patients with active RA and rheumatoid vasculitis also expressed significantly more Fc receptors and less complement receptors on the monocytes than patients with inactive RA. Drug treatment did not correlate with receptor expression or the degradation of aggregated IgG by monocytes either in cross sectional or longitudinal studies. It is concluded that in RA disease activity is related to receptor expression and the degradation of soluble immune aggregates by monocytes. | |
| 2562786 | Gold-naproxen pneumonitis. A toxic drug interaction? | 1989 Jul | A patient with rheumatoid arthritis developed restrictive lung disease and blood eosinophilia. Gold pneumonitis was suspected but the patient did not improve until naproxen was discontinued as well. Lymphocyte transformation studies suggested hypersensitivity to gold. We hypothesize that naproxen unmasked and perpetuated the manifestations of gold hypersensitivity in our patient. | |
| 1908434 | Light- and electron-microscopical study of a case of gold salt-induced hepatotoxicity. | 1991 Sep | A 56-yr-old woman with long-standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exceeded. | |
| 3947143 | Bone metabolism in rheumatoid arthritis compared with postmenopausal osteoporosis. | 1986 Feb | Calcium and bone metabolism in 29 rheumatoid arthritis (RA) patients were compared with those in 27 postmenopausal osteoporotic patients. Signs of vitamin D deficiency were found in 20 RA patients, including 12 who took recommended amounts of vitamin D in their diets and were exposed to sufficient sunlight, and in none of the osteoporotic patients. There were no signs of malabsorption. In six out of 15 patients we found increased liver enzyme activity, which may have a role in vitamin D metabolism. We propose the influence of non-steroidal anti-inflammatory drugs (NSAIDs) on vitamin D metabolism in the liver as a possible explanation. | |
| 2419361 | Shared T cell recognition sites on human histocompatibility leukocyte antigen class II mol | 1986 Mar | Seropositive rheumatoid arthritis (RA) in adult and juvenile patients is associated with the serologic marker HLA-DR4. This association is incomplete; about one-third of the patients lack the disease-associated HLA-DR4 haplotype. The main biological function of class II molecules is to restrict the recognition of antigen by T lymphocytes. We therefore tested the hypothesis that patients with seropositive RA share T cell recognition sites for an unknown antigen and that such T cell "epitopes" are not identified by conventional serologic typing. We generated alloreactive human T cell clones by stimulating peripheral blood lymphocytes of normal donors against a lymphoblastoid cell line from a juvenile patient with seropositive RA. A panel of clones that recognized only HLA-Dw14 cells on a panel of homozygous typing cells was used to analyze class II molecules of adult patients with seropositive RA. By inhibition studies using monoclonal antibodies, the epitopes recognized by the different clones could be further characterized and assigned either to DR- or to DQ-encoded cell surface products. By using four different clones, it was possible to identify Dw14-associated T cell epitopes on all seropositive rheumatoid patients tested who typed HLA-DR4-positive and also on all eight DR4-negative patients tested. Approximately one-half of nonrheumatoid DR4-positive donors carried one or more determinants recognized by these clones; the expression of these allodeterminants in DR4-negative nonrheumatoid patients was rare (less than 10%). Thus, alloreactive human T cell clones are powerful tools to define T cell recognition sites on class II molecules that are not identified by conventional typing. Using T cell clones with specificities for determinants expressed on Dw14 homozygous typing lines, we were able to demonstrate shared epitopes on cells of all patients tested with seropositive RA irrespective of their HLA-D or HLA-DR type. These data suggest that major histocompatibility complex class II antigens of RA patients might be much more homogeneous than demonstrated by the incomplete HLA-DR4 association. | |
| 2382960 | Measurement of conjugated diene lipids by derivative spectroscopy in heptane extracts of p | 1990 May | A series of experiments are described which show that second derivative spectroscopy can be used to quantify conjugated lipid dienes as markers of lipid peroxidation in heptane extracts of plasma from patients with rheumatoid arthritis, osteoarthritis, and healthy controls. Results obtained by this method gave reasonable agreement with those derived from the measurement of simple absorbance in chloroform/methanol extracts. Two minima were observed in the derivative spectrum of plasma lipid extracts. These minima occurred at 233 and 241 nm and corresponded to absorbance maxima in the conventional UV spectrum. Using a combination of phospholipase hydrolysis, reverse phase high performance liquid chromatography (HPLC) and second derivative spectroscopy we confirmed that these two minima can be attributed to a single fatty acid (9 cis-, 11 trans-linoleic acid) shown previously to account for greater than 90% of diene conjugation in human plasma samples. When the biological isomer 9 cis-, 11 trans-linoleic acid was separated by reverse phase HPLC from the mixture of other plasma phospholipid-2-esterified fatty acids we observed a change in derivative spectroscopy minima from 233 and 241 nm to 228 and 237 nm. Minima at the latter two wavelengths were also seen with pure preparations of the Paint Research Isomer (9 trans-, 11 trans-linoleic acid) which eluted later than biological 9 cis-, 11 trans-linoleic acid using reverse phase HPLC, suggesting that the absorption spectra of these pure cis-, trans and trans, trans dienes are similar but can be altered by the presence of other fatty acids in the extract. | |
| 2050468 | Sjögren syndrome: comparative studies in local ocular and serum immunoglobulin concentrat | 1991 May | The objective of the present study was to examine Secretory IgA in tears and serum of Sjögren patients (34 patients and 23 controls). The test was performed in a parallel study using a polyclonal and a monoclonal method (Inter-Assay variation 9.1/Intra-Assay variation 5.5). No differences in the levels of tear secretory IgA were found between patients and controls. In serum however, secretory IgA, total IgA, IgM and IgG showed a significant increase in the Sjögren patients. The fact that secretory IgA levels remain normal in the ocular mucosa of these patients may explain that, despite the autoimmune destruction of the lacrimal gland, humoral defense factors are normally present on the surface of the eye to combat infections. | |
| 3489571 | Anti-DNA antibodies in autoimmune disorders by ELISA using nylon as the solid phase. | 1986 Aug | A rapid, simple and highly sensitive enzyme-linked immunosorbent assay (ELISA) utilizing nylon as the solid support is described for the detection of anti-DNA antibodies in autoimmune disorders. The optimal reaction conditions were established with an anti-DNA antibody-positive SLE serum. Fifty-three percent of systemic lupus erythematosus patients, 29 percent of patients with systemic lupus erythematosus with overlapping progressive systemic sclerosis and 10 percent of progressive systemic sclerosis patients were positive for anti-DNA antibodies. The sensitivity of the method was compared with passive hemagglutination and fluorometric assays, the latter using ethidium bromide as intercalating dye. The method described is specific, reproducible and convenient for use in clinical laboratories where large numbers of samples are to be screened for the detection of anti-DNA antibodies. The procedure requires small quantities of antigen or antibody and is, therefore, highly economical. | |
| 2948274 | T-cell helper activity and B-cell function of synovial and blood lymphocytes from patients | 1986 Dec | The helper effect of T cells on B-cell immunoglobulin (Ig) responses induced by pokeweed mitogen (PWM) or purified protein derivative of tuberculin (PPD) was studied in lymphocytes from synovial fluid (SF) and blood of nine patients with rheumatoid arthritis (RA) and eight patients with other forms of chronic arthritis. In PWM cultures the helper effect of SF T cells on Ig responses (IgG, IgM, IgA) of autologous and allogeneic blood B cells was lower than that of blood T cells (P less than 0.01). This decrease was more pronounced in patients with RA than in patients with non-RA. In PPD cultures no significant difference was found between the helper effect of SF T cells and blood T cells on the Ig responses of allogeneic blood B cells or on the IgG response of autologous blood B cells, whereas the helper effect of SF T cells on the IgM and IgA responses of autologous blood B cells was decreased. The Ig responses to PWM or PPD in cocultures of autologous blood B and T cells were not significantly different between patients and healthy controls. The PWM- and PPD-induced Ig responses of SF B cells were lower than those of blood B cells when cocultured with autologous blood T cells. SF B cells produced IgG but usually little IgM and IgA. Thus there was a dysfunction of SF B cells and of SF T cells in a PWM-driven system, but a fairly good helper function of SF T cells in a PPD-driven system. | |
| 2025768 | Iliac insufficiency fractures. | 1991 Apr | Twenty-five post-menopausal women with one or more insufficiency fractures of the pelvic ring are reported. In 80% of cases the fractures were multiple and a total of 79 insufficiency fractures was identified. Twelve iliac insufficiency fractures were present in 11 patients located at one of three sites: above and parallel to the acetabular roof ("supra-acetabular"), extending diagonally across the iliac ala from the greater sciatic notch ("oblique iliac"), and adjacent to the sacro-iliac joint ("superomedial iliac"). The plain radiographic appearances of these iliac fractures were typically subtle with ill defined medullary sclerosis, due to trabecular compression, the cardinal sign. Scintigraphy revealed the fractures as foci of increased activity which, in the presence of multiple pelvic insufficiency fractures, may be mistaken for metastatic disease. Computed tomography can be helpful in confirming the presence of suspected fractures, revealing further occult fractures and also excluding the likelihood of malignancy. |