Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2764813 | The metabolism of C3 and C4 in patients with immune complexes and normal complement levels | 1989 Apr | The metabolism of the complement proteins, C3 and C4 was examined in two groups of patients with a high incidence of detectable immune complexes but normal levels of complement components. The specific aim was to ascertain whether significant ongoing complement activation occurred in these patients. Eleven patients with rheumatoid arthritis (RA), 11 with infection and 11 control subjects were studied. Each received approximately 10 microCi 125l.C4 and 2.5 microCi 131l.C3 by intravenous injection. Analysis of turnover data showed that there was significant hypercatabolism of both C3 and C4 in the two study groups compared to controls. Plasma production of C4 was normal for both groups (despite the presence of C4 null alleles in six out of 11 of the RA group), while C3 production was significantly elevated in both RA and infection (p less than 0.01 and p less than 0.001 respectively). Patients with infection showed a significant increase in extravascular/intravascular distribution of both proteins. The data show that immune complex formation is associated with accelerated turnover of complement proteins, irrespective of co-existing tissue damage or changes in the serum concentration of complement components. The findings suggest that both activation of complement and maintenance or enhancement of protein synthesis are important for the efficient processing of immune complexes in vivo. | |
| 2355725 | [Thrombocyte function and thrombocyte-associated immunoglobulins in patients with systemic | 1990 May 4 | The investigation of in vitro platelet functions from patients with SLE and rheumatoid arthritis (RA) revealed a distinctly reduced aggregation mass after both collagen und ADP induction. The platelet serotonin contents were significantly decreased in both groups. An "aspirin-like" platelet defect could be excluded by finding a normal malonyldialdehyde release of patients' platelets upon thrombin stimulation. Significantly increased platelet associated IgG was also detected, whereas platelet associated IgM remained within normal limits. These results are interpreted as indicating an ongoing platelet release reaction induced by IgG platelet antibodies, which induce the observed impairment of platelet functions and may also lead to the release of proinflammatory platelet mediators. | |
| 3300660 | Rheumatoid nodules of the spine: case report and review of the literature. | 1987 Jun | We present the case of a patient who had rheumatoid nodules of the vertebrae, which had resulted in bony destruction of the spine at 3 levels. Although there have been only 3 previous reports of such findings with confirmation by histologic analysis, we believe the condition is more common than has been thought. From a review of the literature, we found that similar clinical and radiographic features, as well as descriptions of rheumatoid granulation tissue invading the disc spaces, have been described in several subjects. | |
| 1693338 | Human monoclonal rheumatoid factors derived from the polyclonal repertoire of rheumatoid s | 1990 Apr | A panel of 14 human monoclonal and monoreactive IgM rheumatoid factors (RF) derived from the synovial tissue of rheumatoid arthritis (RA) patients was studied for the expression of cross-reactive idiotopes (CRI) and variable heavy (VH) and variable kappa (V kappa) subgroups. Four of the twelve kappa RF expressed light chains of the V kappa III subgroup. Three of these were characterized as belonging to the V kappa IIIb sub-subgroup, and expressed the V kappa IIIb associated CRI, 17.109. None of the RF expressed the V kappa IIIa-associated CRI, 6B6.6. One of the fourteen RF expressed the VH-associated CRI, G6, and five expressed either or both the VHIII-associated CRI, B6 and D12. Seven RF bound to protein A (SpA), which indicates the expression of VHIII subgroup V regions. Together the data indicated that 9/11 RF express VHIII regions and 2/11 express VHI regions. There was no obvious correlation between V region usage or CRI expression and fine specificity of the RF for human IgG subclasses. These data indicate a difference in V gene usage by RF derived from RA patients compared with RF paraproteins derived from non-RA patients. There is not a bias towards variable chains of the V kappa III subgroup, but a marked preference for variable heavy chains of the VHIII subgroup is seen. Further studies may elucidate the pathological significance of these findings in RA. | |
| 2396862 | Polymorphism of major histocompatibility complex extended haplotypes bearing HLA-DR3 in pa | 1990 Aug | The distribution of DR3 and of extended haplotypes bearing DR3 was studied in three groups of subjects: 35 patients with rheumatoid arthritis (RA) with gold induced thrombocytopenia or proteinuria, 185 patients with RA without these side effects, and 300 normal healthy controls. The extended haplotypes bearing DR3 were analysed with cDNA probes for DR alpha, DR beta, DQ alpha, and DQ beta genes. The data showed that the prevalence of DR3 was significantly higher in patients who developed gold induced thrombocytopenia or proteinuria than in normal controls or patients with RA without these side effects. Distribution of three extended haplotypes bearing DR3 (B8, DR3; B18,DR3; non-B8,non-B18,DR3) in patients with RA with thrombocytopenia or proteinuria was significantly different from that in normal controls, but not from that in patients with RA without these toxic reactions. Southern blot analysis of DR, DQ genes with cDNA probes showed that the extended haplotype bearing B8,DR3, which carries DQA2.1 and DQB2.1 genes, was present in a significantly higher proportion of patients with RA with gold induced thrombocytopenia or proteinuria (22/24, 92%) than in patients with RA without these side effects (32/45, 71%) or normal subjects (40/61, 66%). The data suggest that the genomic region on chromosome 6 involved in susceptibility to gold induced thrombocytopenia or proteinuria should be extended to the DQA2, DQB2 gene loci. | |
| 1966643 | Superoxide scavenging activity of leukocytes in rheumatoid arthritis and Behçet's disease | 1990 May | Superoxide radical anion (O2-) has been suggested to mediate tissue damage associated with chronic inflammatory disorders such as rheumatoid arthritis (RA) and Behçet's disease (BD). Despite that protection from O2- is provided by superoxide dismutase (SOD), there are controversial results about SOD-like activity of polymorhonuclear cells (PMN) in RA and there are no reports about it in BD. In addition, colchicine, a potent inhibitor of phagocytosis, has been used for the treatment of BD, no report about its effect on SOD-like activity of PMN is available. The present study investigates the superoxide scavenging activity (SSA) of PMN and mononuclear cells (MNC) in both RA and BD, and it examines the effects of colchicine on SSA of PMN in BD using the electron paramagnetic resonance/spin trapping method. The SSA of PMN, but not MNC, was significantly lower in patients with either RA or BD, as compared with that in healthy controls. The SSA of PMN in both RA and BD showed a strong negative correlation with that in healthy controls. The SSA of PMN in both RA and BD showed a strong negative correlation with erythrocyte sedimentation rates and C-reactive protein levels. Colchicine treatment increased the SSA of PMN toward normal level in BD patients, and prevented the decrease of SSA in PMN obtained from healthy adults after the stimulation with opsonized zymosan in vitro. Our results suggest that the decrease of SSA in PMN is not disease specific and it is probably the results of the increased amount of O2- generated by these cells.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 1882188 | Localization of circulating immune complexes from patients with rheumatoid arthritis in mu | 1991 Sep | In previous studies we have demonstrated high levels of rheumatoid factor (RF) and large-size (greater than 22S) circulating immune complexes (CIC) in the serum of rheumatoid arthritis (RA) patients with extra-articular disease. These findings were paralleled by a concurrent increase in the level of RF-associated cross-reactive idiotypes (CRI) and an apparent diversification of the RF repertoire detected in the serum of the same patients. In the present study we examine the ability of CICs to activate the complement system in vivo, and its possible influence on expanding the RF repertoire in RA patients with extra-articular disease. Activation of complement by CICs is the key for germinal centre localization and long-term retention of such complexes on the surface of follicular dendritic cells (FDC), and so provides a source for the selection of cells with high affinity receptors for IgG and leads to the establishment of immunological memory. CICs containing different immunoglobulin isotypes and from different patients localized in mouse spleen germinal centres. However, intense localization was mainly seen for IgG-containing complexes from the serum of patients with large-size (greater than 22S) IgG-IgM RF complexes. The ability of these complexes to localize in mouse spleen germinal centres was related to activation of the complement system via the classical pathway in the patients' sera. Localization of IgG complexes was significantly (P less than 0.05) higher in sera from RA patients with extra-articular disease than those with articular disease alone. This study demonstrates the ability of large-size (greater than 22S) IgG-IgM RF complexes to activate complement, and suggests a possible role for such complexes in modulating the immune response to IgG in RA patients with extra-articular disease. | |
| 3515526 | Duration of morning stiffness in rheumatic patients after medication with enteric-coated a | 1986 | Twenty-nine adult rheumatic patients who were taking 500 mg naproxen at bedtime and had a certain degree of morning stiffness despite this medication took part in a randomized double-blind cross-over study in which the duration of morning stiffness after evening doses of 500 mg enteric-coated naproxen tablets was compared with that after identical doses of plain naproxen tablets. The duration of morning stiffness was significantly shorter after taking enteric-coated tablets (p less than 0.01), and the mean plasma naproxen morning concentration was 34% higher (p = 0.01). Since the results were unambiguous in such a small group of patients, they are judged to be of considerable clinical value. | |
| 2187910 | Clinical safety of flurbiprofen. | 1990 Apr | Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid arthritis, osteoarthritis, and other painful musculoskeletal conditions. In these studies serious upper gastrointestinal ADRs occurred in flurbiprofen-treated patients at less than one half the rate seen in aspirin-treated patients. The incidence of serious urinary tract ADRs was lower with flurbiprofen than with aspirin. The flurbiprofen group had no serious clinical ADRs related to the hemic/lymphatic system. The most common laboratory abnormality was a decrease in hematocrit, which occurred less often than in the aspirin group. We also evaluated serious flurbiprofen-related ADRs in 4370 patients in a variety of other studies and reviewed published reports of flurbiprofen clinical trials and case reports. These reviews showed no additional, unanticipated patterns of intolerance. These clinical safety data indicate that in the doses studied, flurbiprofen is a well tolerated agent for patients requiring nonsteroidal antiinflammatory drug therapy. | |
| 2786669 | Effects of diclofenac, indomethacin, tolfenamic acid and hydrocortisone on prostanoid prod | 1989 Mar | Prostanoids, found in enhanced concentrations in rheumatic synovial fluid, are involved in the joint destruction seen in rheumatoid arthritis. Adherent cells isolated from rheumatic synovia produce higher amounts of prostanoids in a primary cell culture than cells originating from non-inflamed synovia. In the present study, it was found that exogenous arachidonic acid diminished the differences in prostanoid production between healthy and rheumatic synovial cells. Non-steroidal anti-inflammatory analgesics in clinically relevant concentrations had similar inhibitory effects on arachidonic acid-stimulated prostanoid synthesis in both healthy and rheumatic cells. In the presence of exogenous arachidonic acid, hydrocortisone (0.3-5.0 microM) did not affect prostanoid production in healthy cells. In rheumatic synovial cells hydrocortisone reduced PGE2 and PGF2 alpha synthesis to about half of the control value and the effect was not reversed by adding excess exogenous arachidonic acid. Altered regulation of phospholipase A2 activity in rheumatic synovia could explain the observed differences between healthy and rheumatic synovial cells. | |
| 2597208 | Interleukin-1-inhibitory IgG in sera from some patients with rheumatoid arthritis. | 1989 Dec | Inhibition of interleukin-1 alpha (IL-1 alpha) activity was detected in 7 of 41 serum samples from patients with rheumatoid arthritis (RA). These 7 sera inhibited not only IL-1 alpha-induced endothelial cell adherence to neutrophils, but also IL-1 beta-induced endothelial cell adherence, although to a lesser extent. These sera showed no influence on tumor necrosis factor-induced endothelial cell adherence. No inhibitory activity was found in 40 sera from normal control subjects. Studies to further examine these effects included gel filtration analysis of 2 of the RA sera. The inhibitory activity was eluted near Mr 158 kd and above Mr 250 kd. Analysis by protein A affinity chromatography showed that IL-1-inhibitory activity was present in protein A-binding fractions. Purified IgG (by DE-52 column chromatography) from RA patients was found to be as potent an inhibitor as the protein A-binding fractions, which suggests that the major inhibitory activity in RA sera is attributable to IgG molecules. These purified IgG molecules also inhibited IL-1-induced proliferation of mouse thymocytes but did not influence IL-2-dependent proliferation of the CTLL-2 murine T cell line. The 7 patients whose sera showed IL-1-inhibitory activity had mild RA and low titers of rheumatoid factor. The findings, taken together, suggest a possible regulatory role of IL-1-inhibitory IgG in RA disease activity. | |
| 2560608 | Effects of inflammation on copper antioxidant enzyme levels. | 1989 | Inflammation increases plasma levels of ceruloplasmin, a copper protein with possible antioxidant function. This paper describes modulation of these increases by copper intake, and describes combined effects of inflammation and copper intake on Cu-Zn and extracellular (EC) superoxide dismutase (SOD) activities. Turpentine injections in rats fed 1 of 4 copper levels increased ceruloplasmin activities, but values were sensitively limited by copper intake. Cu-Zn SOD activities in the liver, but not in erythrocytes or lungs, were reduced by inflammation in each dietary copper group. Inflammation in rats fed a standard mixed feed diet reduced plasma EC superoxide dismutase activities measured by inhibition of pyrogallol autoxidation. Different results were obtained with 3 xanthine oxidase based SOD assays which were each subject to assay interference. Studies in humans found a group of rheumatoid arthritis patients to possess relatively low erythrocyte SOD and relatively high ceruloplasmin activities. Activity levels of SOD, but not of ceruloplasmin, increased after 4 weeks of copper supplementation (2 mg/day). The fate of cellular Cu-Zn SOD activity contents in inflamed tissues is largely uninvestigated. However, interleukin-1, a hormone released at inflammation sites, elevated Cu-Zn SOD activities in cultured fibroblasts. | |
| 3787168 | The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity | 1986 Nov | The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis. | |
| 2459076 | Inosiplex enhances the growth of Epstein-Barr nuclear antigen-positive B-cells from patien | 1988 | The in vitro effects of inosiplex (INO) on proliferation of Epstein-Barr virus (EBV)-carrying B-cells were evaluated. As measured by 3H-thymidine uptake, INO significantly augmented the proliferation of long-term cultured Epstein-Barr nuclear antigen (EBNA)-positive B-cells which were obtained from patients with rheumatoid arthritis (RA) and infectious mononucleosis (IM). In co-culture experiments, INO and anti-immunoglobulin M antibodies coupled to sepharose (anti-mu) had additive effects on proliferation of EBNA-positive B-cells. We conclude that its direct effects on B-cell function should be considered when INO is used for the treatment of diseases characterized by B-cell hyperreactivity. | |
| 2838344 | Clofazimine-mediated enhancement of reactive oxidant production by human phagocytes as a p | 1988 | Clofazimine, at concentrations within the therapeutic range (0.01-5 micrograms/ml), stimulated human polymorphonuclear leucocytes (PMNL) to generate increased amounts of reactive oxidants (RO) when activated with the tripeptide leucoattractant N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP), calcium ionophore, phorbol myristate acetate and opsonised zymosan. Clofazimine per se did not activate the membrane-associated oxidative metabolism of PMNL, but rather primed these cells to hyperreact to the various stimuli. To investigate the therapeutic significance of these observations clofazimine was administered to patients with various chronic inflammatory diseases (lichen planus, discoid lupus erythematosus and rheumatoid arthritis) and generation of RO by FMLP-activated phagocytes was measured before and during clofazimine administration. A statistically significant potentiation of RO generation by FMLP-activated phagocytes was observed during clofazimine administration. Since RO are immunosuppressive and antimicrobial the therapeutic mechanisms of clofazimine may be related to pro-oxidative interactions of this agent with phagocytes. | |
| 3944263 | Electron microscopic study of rheumatoid synovial vasculature. Intimate relationship betwe | 1986 Feb | The relationship between (a) "tallness" and (b) cross-sectional area of the endothelial cells (EC) of postcapillary venules (PCV) and capillaries and the cellular composition of adjacent perivascular mononuclear cell infiltrates in rheumatoid (RA) synovial membrane has been examined by electron microscopy. "Tallness" of the EC was measured as the ratio of the height of the EC to its base (H/B). H/B showed a strong positive correlation with the number and percent of perivascular lymphocytes, i.e., the denser the lymphoid aggregation, the taller the EC. In contrast, H/B showed negative correlations with percent perivascular plasma cells, macrophages, and fibroblast(cyte)s. No such correlations were observed with pericapillary infiltrates. A computer-based morphometric technique yielded similar relationships between the cross-sectional area of the EC and the composition of the perivascular infiltrates. These results indicate that the EC of PCV in lymphocyte-rich areas of synovium tend to be tall and to occupy an increased fraction of the cross-sectional area of the vessel. In contrast, in areas rich in macrophages and plasma cells, EC tend to be flat and to occupy a smaller fraction of the cross-sectional area. PCV in uninfiltrated interstitial areas and in normal synovium had flat EC, and capillaries had flat EC regardless of the character of the surrounding infiltrate. Finally, PCV in lymphocyte-rich areas closely resembled those of tonsil in appearance. Our findings indicate that the PCV of the RA synovial membrane from which lymphocytes emigrate to form perivascular lymphoid aggregates resemble those of lymphoid tissue. They suggest that chronic inflammatory tissue and normal lymphoid tissue share mechanisms of lymphocyte emigration. | |
| 3128273 | Effect of recombinant cytokines on glycolysis and fructose 2,6-bisphosphate in rheumatoid | 1988 Feb 15 | Recombinant-derived human interleukin 1 (IL1) alpha and beta and interferon gamma (IFN-gamma) each produced similar increases in rheumatoid synovial cell (RSC) glycolysis, as judged by increased values for glucose uptake, lactate production and cellular fructose 2,6-bisphosphate [Fru(2,6)P2]. Measurement of Fru(2,6)P2 proved to be the most sensitive parameter for an assessment of glycolysis: IL1 alpha, IL1 beta and IFN-gamma all produced a 3-6-fold increase in this metabolite whereas tumour necrosis factor (TNF alpha) was far less effective. Prostaglandin E production was stimulated predominantly by IL1 alpha and IL1 beta rather than by IFN-gamma or TNF alpha. When combinations of cytokines were examined the addition of IFN-gamma with either IL1 alpha, IL1 beta or murine IL1 produced a synergistic increase in cellular Fru(2,6)P2. The three forms of IL1 increased Fru(2,6)P2 via the same pathway, whereas IFN-gamma acted via a different mechanism. The increase in Fru(2,6)P2 in subcultured RSC produced by addition of medium from a primary culture exceeded the maximal effects of any of the single cytokines studied, suggesting the presence of a mixture of cytokines in the primary RSC culture medium. | |
| 3491412 | Cryoglobulinemias and connective tissue diseases. | 1986 Apr | Cryoglobulinemias in connective tissue diseases (CTD) represent, according to various authors, 12-30% of all cryoglobulinemia cases. Among CTD, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome are the diseases most frequently involved in the presence of cryoglobulins (8-48%). The cryoglobulinemias are mostly of the third type and sometimes of the second type. When clinical symptoms are present, usually they are represented by Raynaud's phenomenon, arthralgias, urticaria, purpura and liver involvement. However, the presence of cryoglobulins in a patient with CTD often does not correlate with clinical picture and other laboratory findings. Eight of our 28 cases (15 SLE and 13 RA) showed third type cryoglobulinemias (7 IgM-IgG and one IgM-IgG-Clq) with a remarkable decrease of serum C4 levels. | |
| 3087367 | Metallothionein in cultured human epithelial cells and synovial rheumatoid fibroblasts aft | 1986 Jun 15 | Radioimmunoassay (RIA) and reversed-phase high-pressure liquid chromatography (HPLC) were used to investigate gold-binding proteins of possible metallothionein (MT) nature occurring upon auranofin exposure of cultured human cells. An epithelial cell line (HE) and two sub-strains were examined. The HEAF sub-strain had been made resistant to 2 mumole auranofin/l culture medium. The resistance was associated with the appearance of gold-binding substances with gel filtration characteristics like MT. The HE100 sub-strain had been made resistant to 100 mumole CdCl2/l and contained high amounts of cytosolic Cd-induced MT. In addition, cultured synovial fibroblasts, derived from normal (SN) and rheumatoid (SRA) synovial tissues, were investigated. Evidence was obtained by RIA that the low molecular weight (mol.wt. 6000-7000) gold-binding proteins occurring in the HEAF cells and SRA cells following auranofin exposure, were of MT nature. The relative amounts of MT in the epithelial cell lines were: HE:HEAF:HE100 = 1:18:100. The relative amounts in the synovial fibroblasts were: SN:SRA:SRA treated with auranofin = 1:3:10. The HPLC methods used were found suitable for isolation of Cd-MT in the HE100 cells, but not for the Au-MT in the HEAF cells. By HPLC, the Cd-MT in the HE100 cells was resolved into 3 MT-1 and 1 MT-2 iso-proteins exhibiting the amino acid composition typical of MT. Judged by HPLC, the MT in these cells constituted 0.4% of the cytosolic proteins. | |
| 2149663 | What do chronic pain patients think of their pain? Towards a pain cognition questionnaire. | 1990 Nov | The three-systems model of chronic pain emphasizes the partially independent relationship among physiological, gross motor and verbal-cognitive responses of chronic pain patients. This study describes the development of an assessment instrument representing a measure for the verbal-cognitive response system of chronic pain. Fifty items, each of which is assigned to one of five factors (pain impact, catastrophizing, outcome efficacy, acquiescence and reliance on health care) constitute the new Pain Cognition List (PCL). The PCL was developed using a Dutch back pain population and proves to be stable across sex and back pain diagnosis. By means of three experiments the PCL is shown to be reliable and sufficiently valid. The PCL might be a promising tool for identifying pain patients whose pain problem is mainly controlled by cognitive factors. |