Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3119021 | The natural course of gold nephropathy: long term study of 21 patients. | 1987 Sep 26 | To clarify the natural course of gold nephropathy and thereby facilitate its clinical management 21 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular sodium aurothiomalate were studied in detail throughout their renal illnesses. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 60 months (range 16-130 months). Ten patients developed proteinuria after six months' treatment, 15 after 12 months, and 18 after 24 months. When treatment was stopped the proteinuria reached a median peak of 2.1 g/day (range 0.7-30.7 g/day) at two months (range 1-13 months) before resolving spontaneously, in eight patients by six months, in 13 by 12 months, and in 18 by 24 months. All patients were free of proteinuria by 39 months, the median duration being 11 months. The median first and last measurements of creatinine clearance showed no significant change (77 ml/minute and 59 ml/minute, respectively), and no patient died from or needed treatment for renal failure. HLA-B8 or DR3 alloantigens, or both, were identified in seven patients. Renal biopsy specimens showed membranous glomerulonephritis in 15 patients, a minimal change nephropathy in two, mesangial electron dense deposits in two, and no appreciable glomerular changes in two. In these 21 patients the proteinuria of gold nephropathy resolved completely when treatment was withdrawn. Renal function did not deteriorate, corticosteroids were unnecessary, and several different renal lesions were seen. | |
| 1997647 | Constitutive production of inflammatory and mitogenic cytokines by rheumatoid synovial fib | 1991 Mar 1 | Conditioned media obtained from fibroblasts cultured from rheumatoid and certain other inflammatory synovia were observed to stimulate [3H]thymidine incorporation in an indicator murine fibroblast line. Synovial fibroblasts derived from the joints of patients with osteoarthritis did not display this property. This effect persisted in culture for many weeks and occurred in the absence of co-stimulatory immune cells. Antibody neutralization studies implicated a role for basic fibroblast growth factor (bFGF), transforming growth factor beta (TGF-beta), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin 1 beta (IL-1 beta) in the increased proliferative activity of synovial fibroblast-conditioned media. Synovial cell synthesis of bFGF, TGF beta 1, GM-CSF, IL-1 beta, and IL-6 was confirmed by 35S-methionine labeling and immunoprecipitation. The constitutive production of inflammatory and mitogenic cytokines by synovial fibroblasts may represent the result of long-term, phenotypic changes that occurred in vivo. Persistent cytokine production by synovial fibroblasts may play an important role in the continued recruitment and activation of inflammatory cells in chronic arthritis and in the formation of rheumatoid pannus. | |
| 3489272 | Properties and reactivity of immune complexes in rheumatoid synovial fluid. | 1986 | Fractionation of immune complexes (IC) from rheumatoid synovial fluid revealed the presence of three different fractions of IC. The largest molecular weight form, fraction I (above 1000 Kdaltons) was predominately composed of IgG and IgM and contained both IgM-RF and IgG-RF. The other IC, fraction II (480 Kdaltons) and fraction III (330 Kdaltons), contained predominately IgG with some IgA and only significant amounts of IgG-RF. All three fractions of IC can bind Clq and stimulate human monocyte prostaglandin E (PGE) production. Fraction I IC bound Clq most readily while fraction III IC were the most effective stimulators of monocyte PGE production. IC stimulation of monocyte PGE production was inhibited by staphylococcus protein A suggesting mediation via activation of Fc receptors. It remains to be determined whether this IC reactivity has any pathologic significance. | |
| 2510332 | Role of endothelium in chronic inflammation. | 1989 | The character of the immunologically stimulated chronic inflammatory infiltrate is to a considerable extent determined by nonspecific factors governing mononuclear cell traffic. The volume, composition and distribution of this traffic is strongly dependent on an initial adhesive interaction between circulating mononuclear cells and the EC of the PCV of the involved tissues. The emigration of lymphocytes from the PCV is preceded by binding of the lymphocytes to the endothelial lining cell. This binding is enhanced by lymphokines (IFN-gamma, TNF-beta) and monokines (IL-1, TNF-alpha), secreted by perivascular inflammatory cells and acting on the EC. This enhancement may permit an initial, immunologically generated small focus of mononuclear cells to amplify itself to a larger infiltrate. Movement of the EC-bound lymphocyte through the endothelium may be facilitated by IFN-gamma, as suggested by evidence that T cells, bound to the surface of EC monolayers overlying nitrocellulose filters, migrate through these monolayers in increased numbers in the presence of IFN-gamma. Movement of the lymphocyte through the wall of the PCV and subsequently through the perivascular space toward the inflammatory focus may be enhanced by the chemotactic action of IL-1, generated by the macrophages of the perivascular infiltrate. The lining layer of the synovial membrane may play an important role in the development of synovitis. Hyperplasia of the synovial lining layer is associated with the secretion of chemotactic agents which can attract monocytes from the PCV toward the lining. The continuous movement of monocytes from PCV to lining may establish a steady-state population of macrophage-like cells in the interstitium of the synovium. These may provide the accessory cell population required for the immune responses which give rise to the various chronic inflammatory synovitides. The sublining layer of the rheumatoid synovium does, in fact, contain large numbers of DR+macrophage+ cells which may represent this accessory cell population. Since the cytokines mediate the inflammatory effects of the cellular immune response, it follows that when injected intraarticularly they should produce synovial inflammation. Such inflammation has, in fact, been produced in experimental animals by the intraarticular injection of supernatants of antigen-stimulated PBMC or of rIL-1. A cytokine-mediated chronic inflammatory reaction may be expected to assemble a polyclonal population of lymphocytes around the PCV. However, the fraction of the accumulated T cells which is antigen reactive is not entirely a random one as indicated by the following.(ABSTRACT TRUNCATED AT 400 WORDS) | |
| 3630862 | PAF-acether in chronic arthritis. | 1987 Jun | Platelet activating factor (PAF-acether) is a potent pro-inflammatory mediator. The possible involvement of this molecule in the pathogenesis of chronic erosive arthritis has been investigated using an animal model, antigen-induced arthritis in the rabbit, which closely resembles rheumatoid arthritis. The arthritic joint fluids from rabbits with antigen-induced arthritis contained low levels of PAF-acether in the acute stages of the disease. However, PAF-acether was not detectable in the chronic stages of the lesion. The biologically inactive precursor/metabolite of PAF-acether, lyso-PAF-acether, was detectable in both control and arthritic joint washes. However, the levels of lyso-PAF-acether in the arthritic joint fluids were significantly elevated above those of control in the acute stages of the disease, but not in the chronic stages. Intra-articular injection of PAF-acether at doses up to 100 times the levels detected in the acute stages of this model did not induce joint swelling or leucocyte accumulation in normal rabbits. This study suggest that PAF-acether may contribute to the acute phase of antigen-induced arthritis but is less likely to be involved in the chronic processes. | |
| 2505790 | Cytokine production in culture by cells isolated from the synovial membrane. | 1989 Jun | Cytokine expression was investigated in synovial cell cultures isolated from diseased joints of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Tumour necrosis factor alpha (TNF alpha) was produced spontaneously at high levels by both RA and OA synovial cells. There was no correlation between cell composition and level of TNF alpha produced. In contrast, lymphotoxin (LT) and Interferon gamma (IFN gamma) (greater than 50 pg/ml) were not found. This was further investigated in the RA cultures at both the mRNA and protein level. The results indicated that high levels of mRNA were produced spontaneously by these cells, but the relevant protein was undetectable. The presence of inhibitors and/or shed receptor is unlikely to account for undetectable LT as most of the recombinant LT added to the cultures could be recovered. In addition, in some cases this resulted in an increase in IL-1 production indicating that LT is biologically active in this system. It is not clear at this stage why the protein for these mediators (produced by activated T cells) are not found in the rheumatoid cultures, although it may be due to a post-transcriptional mechanism. This possibility is currently being investigated in addition to the development of more sensitive assays for these cytokines. | |
| 3046970 | Insulin autoantibodies and insulin assay. | 1988 Oct | Insulin antibodies are known to interfere with the radioimmunoassay of insulin. We tested intravenous glucose tolerance on 25 insulin autoantibody-positive (IAA+) patients and 25 IAA- controls, who were matched for sex, age, and body mass index, to establish if IAA could also interfere with insulin assay. Insulin content was measured in untreated serum, serum precipitated with polyethylene glycol (PEG, free insulin), and serum extracted with acid and precipitated with PEG (total insulin). The mean untreated first-phase insulin response (I1 + 3) for IAA+ patients was 172 +/- 67.3 mU/L, significantly higher than the mean control value of 108 +/- 47.5 (P less than .001). After PEG precipitation, mean I1 + 3 in the patient group fell significantly to 105 +/- 48.4 mU/L (P less than .001), but the control value was unchanged (104 +/- 45.5). The mean percentage fall after PEG precipitation was 36.9% (patients) and 2.9% (controls) (t = 8.3, P less than .001). There was a strong correlation between the IAA titer and the interference in the insulin assay (r = .81). After total insulin extraction of IAA samples, there was a significant fall in mean I1 + 3 to 134 +/- 55.4 mU/L (P less than .001), but the control value was unchanged. IAA can significantly falsify insulin measurement, and care must be taken in the interpretation of insulin-release tests when IAA is present. | |
| 3698385 | Bone remodeling phenomena in flexible implant arthroplasty in the metacarpophalangeal join | 1986 Apr | The durability of any implant procedure is related to the host bone tolerance. This can be evaluated in part by measuring the cortical bone thickness around the device. The purpose of this study is to evaluate the long-term bone response to silicone implants at the metacarpophalangeal joint level in a series of 133 digits with a minimum of five years of follow-up evaluation. A method of bone morphometry that can measure cortical bone thickness on radiograms was used. Bone remodeling resulted in the formation of a newly formed cortical bony shell around the implant stems and maintenance of the shape of the cut end of the bone with thickening of the cortical bone at the metacarpal and phalangeal metaphysis. Thickening of the phalangeal midshaft was also present. A postoperative decrease of the metacarpal midshaft cortical bone thickness was related to the surgical reaming and remained permanently. Compared with the initial postoperative length, there was no shortening of the proximal phalanx and an average shortening of 9.1% in the metacarpal. The shape of the cortical bone in implant resection arthroplasty can be maintained and the bone thickness increased. | |
| 3013923 | High IgM antibody to human T-lymphotropic virus type I in systemic lupus erythematosus. | 1986 May | Twenty-six percent of 53 systemic lupus erythematosus sera had high levels of IgM antibody to human T-lymphotropic virus Type I, significantly more than the 5% of normal controls. Neither IgG antibodies to Type I virus nor IgM or IgG antibodies to Type II virus were increased in lupus. Further analysis using competition immunoassay and Western blot techniques also suggested that the IgM Type I antibodies in lupus sera were directed against viral antigens but did not completely exclude a nonviral reaction. Other studies also have not found IgG antibodies to the Type I virus but have not tested for IgM antibodies. Our study suggests that human T-lymphotropic virus Type I or a related virus may be involved in the pathogenesis of some cases of systemic lupus erythematosus. | |
| 2769647 | Oestrogen induced suppression of collagen arthritis. IV: Progesterone alone does not affec | 1989 May | The effects of 17 beta-oestradiol and progesterone on the development of type II collagen-induced arthritis (CIA) and the anti-type II collagen (CII) autoantibody response were investigated. Treatment with physiological doses of 17 beta-oestradiol, inducing serum levels below the estradiol peak at the end of pregnancy, abrogated the development of arthritis and suppressed the anti-CII autoantibody response. Treatment with progesterone alone did not have significant effects on the development of arthritis or on the anti-CII autoantibody response. However, a combined treatment with both progesterone and oestrogen in physiological doses induced a more pronounced suppression of CIA than the suppression induced with oestrogen treatment alone. These findings suggest that oestrogen, but not progesterone, may be the critical factor to explain the pregnancy-related down-regulation of CIA. | |
| 2479386 | Antigenic specificity of rheumatoid synovial fluid lymphocytes. | 1989 Nov | The majority of rheumatoid arthritis (RA) synovial fluid lymphocytes (SFL) demonstrate markers that are suggestive of prior activation. While the mechanism(s) responsible is unknown, prior studies have suggested that certain Mycobacterium tuberculosis (MT) antigens may preferentially activate SFL in vitro. We therefore examined the ability of RA SFL to respond to purified protein derivative and an acetone-precipitable MT antigenic complex (AP-MT) and compared this with the responses by peripheral blood lymphocytes (PBL). The responses were contrasted with those elicited with tetanus toxoid (TT) and mitogenic anti-CD3. In patients with RA, the SF proliferative responses to both TT and anti-CD3 were reduced compared with responses by PB. In contrast, the SF response to purified protein derivative was maintained, and that to AP-MT was significantly increased, compared with PB. SF responses to AP-MT antigens were significantly greater than those to TT. The AP-MT activation of T lymphocytes from RA SF was characterized by an earlier peak proliferative response than that noted with matched PB. AP-MT responsiveness was not restricted to HLA-DR4 positive patients. These observations suggest that an epitope(s) contained within the MT complex of antigens, and enriched in the AP-MT complex, may be important in maintaining the chronic inflammation in at least some patients with RA. | |
| 2925633 | Structure and properties of a human non-pancreatic phospholipase A2. | 1989 Apr 5 | We have purified a human non-pancreatic phospholipase A2 that is present in platelets and is enriched in rheumatoid synovial fluid. The enzyme is calcium-dependent, has a pH optimum of 8-10, and shows a striking preference for substrate presented in the form of Escherichia coli membranes. In the E. coli phospholipase A2 assay the phospholipase exhibits an apparent specific activity of 300 mumol/mg/min. Using oligonucleotide probes based on amino-terminal sequence data, we cloned the corresponding human gene from a genomic DNA library and expressed the gene in animal cells. The protein was secreted from the cells in an active form. The deduced amino acid sequence of the human protein consists of 124 amino acids, contains structural features common to all known phospholipase A2s, and has a half-cystine pattern that is characteristic of the snake venom group II enzymes. | |
| 2925608 | Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic syn | 1989 Apr 5 | Synovial fluid from arthritic patients contains multiple forms of phospholipase A2 (PLA2), as resolved by high performance liquid chromatography (Seilhamer, J.J., Plant, S., Pruzanski, W., Schilling, J., Stefanski, E., Vadas, P., and Johnson, L. K. (1989) J. Biochem. (Tokyo), submitted for publication). Here we describe the cloning of a human 4.5-kilobase gene and 800-base pair cDNA encoding the form representing the major peak of activity and protein mass (peak A). The clones encode a mature peptide of 124 amino acids, which follows a prepeptide of 20 residues. The deduced amino acid sequence constitutes an enzyme of the "Type II" class of PLA2s, and resembles PLA2s from other mammalian sources. This represents the first report of a full length mammalian non-pancreatic PLA2 sequence. Active transcription of this PLA2 gene was detected in two different inflammatory cell sources. Recombinant human peak A PLA2 was expressed in vaccinia as a secreted protein which accumulated in conditioned medium. | |
| 2843076 | Reduction of monocyte 5'nucleotidase activity by gamma-interferon in multiple sclerosis an | 1988 Jul | Ecto-5'nucleotidase (5'NT) activity in the plasma membrane of peripheral blood monocytes from patients with multiple sclerosis (MS), rheumatoid arthritis (RA), myasthenia gravis (MG), motor neuron disease (MND), and from normal control subjects of similar age was determined by radioisotopic assay. The activity in unstimulated monocytes cultured for 24 and 48 hours was found to be higher than normal in 56% of patients with active relapsing MS, 29% of patients with RA, and 7% of patients in the MG/MND group. While the enzyme activity was reduced after cultivation of the cells with recombinant interferon-gamma (gamma-IFN) in all of the groups studied, the percentage reduction was significantly greater in monocytes from patients with active relapsing MS who were in relapse at the time of sampling (p = 0.03). HLA-DR expression was monitored using immunofluorescence staining with monoclonal antibody and showed that similar numbers of monocytes in all patient and control groups expressed this antigen. Thus, while high monocyte 5'NT activity was found principally in patients with active relapsing MS and in some patients with RA, the monocytes from patients with MS were, in addition, exquisitely sensitive to stimulation with gamma-IFN. | |
| 2431452 | Immunogenic and antigenic epitopes of immunoglobulins. XVII--Monoclonal antibodies reactiv | 1986 | Two mouse hybridoma antibodies, G6 and H1, with specificity for idiotypic determinants on the heavy chain of human IgM-RF have been produced. Idiotopes recognized by G6 and H1 were expressed on 5/12 and 2/12 RF paraproteins from the Wa idiotype group respectively, but not on paraproteins lacking rheumatoid factor (RF) activity. Inhibition experiments demonstrated that G6 and H1-specific epitopes were located on (or close to) the antibody binding site of RFs, and measurable on the heavy chain but not their light chains. However, it was concluded that the quaternary structure of the antibody-binding site was important for the optimal expression of both idiotopes. The idiotope recognized by G6 was also detected on polyclonal RFs in unfractionated sera from 8/14 patients with rheumatoid arthritis (RA). The results suggest that the G6 idiotope is a highly conserved determinant on the antibody-binding site of RF. These monoclonal antibodies will allow characterization of RF clonality in RA. | |
| 3259718 | [Plasma levels of vitamins A and E in hyperostosis, ankylosing spondylarthritis and rheuma | 1988 Mar 15 | In animal and man, chronic intoxication with vitamin A or retinoids may be responsible for vertebral hyperostosis and periosteal appositions. Vertebral hyperostosis is found in hyperostotic disease but also in the course of ankylosing spondylarthritis. Therefore, we felt it would be interesting to study blood retinol levels in 22 patients with hyperostotic disease, 29 patients with ankylosing spondylarthritis, 18 patients with rheumatoid polyarthritis and 21 reference patients. The Kurskal-Wallis test has demonstrated a significant difference of blood retinol levels between these four groups (p less than 0.0001). The blood retinol level was more elevated during hyperostotic disease (3.63 +/- 1.13 mumol/l) than in the reference group (2.94 +/- 0.76) and was, on the contrary, lower during ankylosing spondylarthritis (2.57 +/- 0.66) and rheumatoid polyarthritis (2.32 +/- 0.64). This study confirms the elevation of blood retinol during the course of hyperostotic disease; such a abnormality was not demonstrated in the course of ankylosing spondylarthritis, and on the contrary, suggest that a decreased blood retinol level may be observed during chronic inflammatory rheumatic diseases such as rheumatoid polyarthritis or ankylosing spondylarthritis. | |
| 3494784 | An enzyme-linked immunosorbent assay for the detection and quantitation of anti-Jo-1 antib | 1987 Apr 16 | We have developed an enzyme-linked immunosorbent assay (ELISA) specific for autoantibodies directed against the autoantigen Jo-1 (histidyl-tRNA synthetase) using antigen prepared biochemically from HeLa cells. No other patient sera, including those containing antibodies directed at threonyl-tRNA synthetase or alanyl-tRNA synthetase, reacted in the assay. Screening of sera from 169 patients with a variety of autoimmune and neuromuscular diseases confirmed that anti-Jo-1 antibodies are confined to a subgroup of patients with pure polymyositis, pure dermatomyositis, or myositis associated with another rheumatic disease. | |
| 2785142 | Binding of complement components C1q, C3, C4 and C5 to a model immune complex in ELISA. | 1989 Apr 21 | When normal human serum is added to microELISA plates coated with monomeric or aggregated IgG various complement components become bound and can be detected with specific chicken anti-C1q, anti-C3, anti-C4 and anti-C5 antibodies. Using such assays we found increased C1q- and decreased C3- and C4-binding in sera from patients with SLE. In contrast, sera from patients with rheumatoid arthritis showed decreased C3 binding but normal C1q binding. The decreases in C3 and C4 binding observed in the sera from patients with SLE were larger than the corresponding decreases determined by radial immunodiffusion. Comparing these results with those of the CH50 assay, the correlation coefficient between CH50 and the C3-binding assay was 0.48. There was no correlation between the results of the CH50 and those of the C1q-, C4- or C5-binding assays. | |
| 1829991 | Detection of circulating Fc epsilon R2/CD23+ monocytes in patients with rheumatic diseases | 1991 Jul | Recently, in vitro studies have demonstrated that expression of Fc epsilon R2/CD23 on normal monocytes can be specifically induced by IL-4. In order to investigate the interaction of IL-4 and monocytes in rheumatic diseases, flow cytometry studies were performed. Elevated numbers of circulating Fc epsilon R2/CD23+ monocytes were detected in patients with progressive systemic sclerosis (PSS) as compared with controls. In addition, supernatants derived from phytohaemagglutinin-stimulated peripheral blood mononuclear cells of PSS patients contained high activity to induce Fc epsilon R2/CD23 on CD14+ monocytes. An increased frequency of Fc epsilon R2/CD23+ monocytes was also observed in rheumatoid arthritis, and sequential studies in patients with systemic lupus erythematosus showed a close relationship between Fc epsilon R2/CD23+ monocytes and disease activity. It is suggested that IL-4 has an important role in the pathogenesis of PSS by activating monocytes, and might also contribute to monocyte activation in other rheumatic diseases. | |
| 2902897 | Effect of sulphasalazine and its metabolites on mitogen induced transformation of lymphocy | 1988 Oct | The effects of sulphasalazine (SASP), sulphapyridine (SP), and 5-aminosalicylic acid (5-ASA) have been studied on mouse spleen cells cultured in the presence of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and lipopolysaccharide (LPS). SASP exhibited a significant degree of suppression, at doses in the range 25-100 micrograms/ml (p less than 0.01), this suppression being greater than 50% at 50 micrograms/ml. SP exhibited only a minor degree of suppression (10% at 75 micrograms/ml, p less than 0.01). Coadministration of a non-steroidal anti-inflammatory drug (NSAID), indomethacin, produced no evidence of further suppression in the presence of SASP or SP. Administration of SP plus 5-ASA to parallel cultures that were profoundly suppressed by the molecular equivalent amount of SASP resulted in no suppression. This implied requirement of the intact parent molecule (SASP) to produce this effect, at these concentrations. The concentration of SASP required to produce more than 50% suppression was higher than that ever attained in the peripheral blood of humans receiving therapeutic doses of the drug. Human lymphocytes are similarly suppressed by SASP, but only at higher concentrations than are required for murine cells. Thus, if the parent drug is the active moiety and requires these concentrations to be effective in vivo, it follows that the site where these effects may be mediated is likely to be the intestinal tract. The effects described would suggest the gut associated lymphoid tissue as a likely target. |