Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2387743 | Rhenium heptasulfide: a potential carrier system for radiation synovectomy. | 1990 | Rhenium sulfide colloid was prepared by the thiosulfate acid reduction method and assessed for its applicability as a particle carrier for use in radiation synovectomy. In vitro stability studies demonstrated that greater than 95% of the 186Re activity remained in colloidal form over a 5 day period. Intraarticular knee injections of 186Re2S7 into normal and arthritic rabbit joints were followed by gamma camera imaging and by biodistribution in order to quantify the leakage to different organs. Mean retentions of 186Re in knees, determined by gamma camera imaging were 97(+/- 4)%, 92(+/- 7)%, 89(+/- 9)% and 88(+/- 10)% at 1 h, 1, 2 and 3 days, respectively. The percent injected dose was 0.0023% in the lymph nodes, 1.65% in the liver, 0.006% to the spleen, 0.013% in the lungs, 0.35% in the kidney, 0.014% in the heart, 0.12% in the bone, 0.7% in the muscle, 0.3% in the fat and 0.6% in the blood. | |
| 2802969 | The presence and significance of some anti-enzyme antibodies (anti-plasminogen, anti-tryps | 1989 Jan | It is a well known fact that during the course of RA and rA, due to some cellular and molecular mechanisms, a number of proteolytic enzymes and membranal phospholipases are either activated or their concentration rises significantly. With this aim in view in the present work we have aimed to investigate if, in an inflammatory process associated to RA and rA, the human organism produces or not anti-enzyme antibodies. Using an enzyme-linked immunosorbent assay (ELISA), in the sera of 19 patients of RA and 19 of rA, the presence of the following antibodies has been ascertained: antiplasminogen (antiPAb), antitrypsin (antiTAb) and antiphospholipase C (antiPLCAb). Out of RA cases, 47.3% presented antiPAb, 36.8% antiTAb and 26.3% antiPLCAb. As it was expected, in the rA cases, these antibodies were found in a higher proportion of cases, i.e.: 85.7%, 71.4% and 57.1% respectively. When following the same cases before and during or after the treatment with nonsteroidal antiinflammatory agents (NSAIAs), the antibodies levels were significantly decreased especially in the RA cases. The results obtained indicated a significant rise of seric concentration of antiPAb, antiTAb and antiPLCAb, as well in RA as in rA. While the rise of antiPLCAb in RA and especially in rA could be explained due to microbial infections, the rise of the antiproteolytic enzymes antibody levels as well as the decrease of the antibody titres during or after NSAIAs treatment could be explained, in our opinion, on the basis of some autoimmune processes. | |
| 3089651 | Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by syn | 1986 Apr | Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA) and reactive oligoarthritis were investigated for activated T cells (Ia+SIg-), IL-2 receptor bearing cells (Tac+) and IL-2 production in vivo and in vitro. In contrast to negative results with blood, the synovial fluid of the arthritic joints contains considerable amounts of IL-2 activity (median: 11.8 mu/ml), elevated proportions of Ia+SIg- activated T cells (median: 12.5%) and of IL-2 receptor bearing cells (median: 2.5%). In vitro, after stimulation with several Concanavalin A (Con A) doses, SFL develop proportions of IL-2 receptor cells comparable to PBL. Furthermore, they produce higher values of IL-2 activity than comparable PBL cultures. The proportions of Ia+SIg- activated T cells increase only moderately after Con A stimulation compared to in vivo data, indicating different activated T cell subsets in the synovial fluid (Ia+SIg-, Tac+). The findings are discussed as an expression of an acute hyperactivation of lymphocytes in an inflamed joint. | |
| 2029276 | Pregnancy outcome following first trimester exposure to chloroquine. | 1991 May | Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy. | |
| 1883698 | Bone physiology. | 1991 Jun | Marked improvement in the knowledge of bone physiology has occurred during the last few years. In particular, the development of immunology of bone leads to better understanding of bone cell origin and lineage. At the same time, development of biochemical markers of bone formation and resorption activities allows for better analysis of several pathologic conditions. | |
| 2877853 | Side effect profile of 200 patients with inflammatory arthritides treated with sulphasalaz | 1986 | The side effect profile of sulphasalazine was documented in 200 patients with inflammatory joint disease treated with the drug for at least 1 year. Fifty-eight percent of patients developed one or more adverse reactions and in 21.5% the drug was withdrawn. A further 28% continued taking the drug at a reduced dose. Five percent of the side effects were judged to be potentially serious. In all patients the reactions subsided on either discontinuation of the drug or reduction of the dose. Gastrointestinal (33%) and central nervous system reactions (19%) were the most common, but all were relatively minor. Neutropenia (2%), thrombocytopenia (1%) and pan-hypogammaglobulinaemia (1%) were potentially the most serious effects. The side effect profile of sulphasalazine in inflammatory joint disease appeared to be similar to that in inflammatory bowel disease, but reactions were more frequent in inflammatory joint disease. Enteric-coated sulphasalazine is a useful addition to the small number of slow acting antirheumatic drugs, and in view of its established efficacy, its level of toxicity was found to be 'acceptable' as long as patients were carefully monitored and regular blood tests were carried out. | |
| 2691154 | Cytotoxic drugs in systemic autoimmune diseases. | 1989 Sep | Inhibition of cell proliferation, together with the depression of synthesis of non-specific and specific cellular products, are the modes of action of cytotoxic drugs. In systemic autoimmune diseases these actions result in immunosuppressive and anti-inflammatory effects. The adoption of cytotoxic treatment, as well as the choice of the cytotoxic agent and therapeutic strategy in individual patients, depend on the disease status, on the patient's tolerance to previously administered drugs and on the theoretical risk of major side effects. The oncogenic risk and its relationship with the cumulative dose or the duration of traditional administration schedules must be taken into account, even if this is not constant for all cytotoxic drugs. Both in life-threatening and in seriously disabling systemic autoimmune diseases cytotoxic drugs are employed, according to general guidelines, to induce complete or partial remission of active disease in patients intolerant or refractory to corticosteroids and/or to other disease-modifying drugs. Combinations of cytotoxic drugs and other non-specific immunosuppressive agents as well as innovative therapeutic regimens (pulse therapy, alternation of treatments) have been used with encouraging results: in the future cytotoxic drugs may perhaps be used in association with specific immunosuppressive agents in a complementary combination to halt pathologic processes in systemic autoimmune diseases. | |
| 3677509 | A histologic comparison of aseptic loosening of cemented, press-fit, and biologic ingrowth | 1987 Dec | The histology of interface membranes from aseptic loosened prostheses of various types including cemented, press-fit, and biologic ingrowth varieties was compared. Pseudosynovial implant-facing surfaces were present in specimens from all types. The remaining portions of these membranes showed distinct characteristics as well. Cemented implant membranes contained many macrophages and giant cells and evidenced frequent granuloma formation. Press-fit membranes consisted of poorly vascularized, dense fibrous tissue within the loosened press-fit membrane. Macrophages and giant cells were rare, except in one specimen containing ceramic debris particles. Biologic ingrowth membranes were the most vascular and contained loosely organized connective tissue and islands of woven bone. Macrophages were common. One out of six specimens from patients with rheumatoid arthritis contained massive numbers of lymphocytes and plasma cells but not mast cells. The greatest numbers of mast cells were present in membranes from patients with osteoarthritis and in all cases were associated with the presence of stainless steel and/or chrome cobalt particles. | |
| 3070726 | Quantitation of IgM, IgA and IgG rheumatoid factors by ELISA in rheumatoid arthritis and o | 1988 | We describe the evaluation of an enzyme-linked immunosorbent-assay (ELISA) for the measurement of IgM, IgA and IgG rheumatoid factor (RF). Results were obtained from sera of normal controls and patients with different rheumatic disorders in a cross-sectional study. Both human and rabbit IgG could be used as antigen in the assays. IgA-RF and IgG-RF were measured after pepsin digestion. The WHO reference preparation was used to standardise IgM-RF, but could not be used in the IgA- and IgG-RF assay, because neither IgA- nor IgG-RF could be detected in this standard serum. The ELISA for detection of RF is a highly sensitive and reproducible method and quantitation of results can be standardised. It yields good discriminative values for RA versus controls, in particular when more RF-isotypes are determined. In RA patients a correlation between IgM-, IgA- and IgG-RF concentrations does exist, although a wide variation was found in the ratio of these concentrations. | |
| 2676648 | Salsalate in the treatment of rheumatoid arthritis: a double-blind clinical and gastroscop | 1989 Jul | A double-blind, double-dummy controlled study to compare the clinical efficacy and gastric tolerability of salsalate and piroxicam in the treatment of rheumatoid arthritis was performed. A total of 23 patients were treated with 1.5 g salsalate twice daily and 20 with 20 mg piroxicam (after the evening meal) for 4 weeks. Patients were submitted to gastroscopy at the start and end of treatment; only patients who presented a normal baseline gastroscopy were admitted to the trial. At the end of the planned treatment period, a statistically significant improvement of all clinical variables was observed in both treatment groups, the difference between the two drugs not being statistically significant. Five of 20 (25%) piroxicam treated patients and only 2/19 (11%) salsalate treated patients showed gastric lesions at final endoscopy. No relationship was found between dyspeptic symptoms and endoscopic lesions. The results show that salsalate and piroxicam have equal efficacy in relieving arthritic symptoms, but salsalate causes fewer gastric lesions. | |
| 2462501 | Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. | 1988 Nov | High levels of interleukin 6 (IL 6/B cell stimulatory factor-2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL 6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL 6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL 6. The data indicate that IL 6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL 6 can function as B cell growth and differentiation factor as well as hepatocyte-stimulating factor. | |
| 1913009 | Venostasis, subclinical vasculitis and von Willebrand factor antigen. | 1991 Oct | Von Willebrand factor antigen (VW FAg) has been used as a marker for vasculitis and raised levels have been shown to correlate with active disease. The use of VW FAg levels in the diagnosis of vasculitic disorders has been proposed. However, certain cases of vasculitis have normal VW FAg levels and are difficult to diagnose; this is of importance because of the high mortality associated with these disorders. It has been suggested that venostatic stress can be used as a provocative test for stimulating VW FAg release, thereby improving the speed and sensitivity of diagnosis. We tested this hypothesis in a mixed group of 35 patients with vasculitis, systemic lupus erythematosus and rheumatoid arthritis and 16 controls. At baseline, although the levels were not outside the laboratory range, the disease groups had raised VW FAg compared with the simultaneously tested controls. Venostatic stress increased VW FAg activity in all disease groups, control levels also increased and differences between controls and disease groups diminished in significance. Therefore venostatic stress with VW FAg measurement does not produce a more sensitive test for vasculitis. Venostasis should be avoided when measuring VW FAg levels. | |
| 3397964 | Ultrastructure of skeletal muscle in rheumatoid myositis. | 1988 Apr | Muscle biopsies from 8 cases of rheumatoid myositis (5 females and 3 males) were studied by electron microscopy. All muscle fibers studied showed either necrosis or atrophy, the latter varying from slight to severe. Mononuclear cell infiltration was present in all cases, with 4 types of cells observed (lymphocytes, plasma cells, macrophages and mast cells). The capillary endothelium showed proliferation of organelles, occlusion of lumina, and thickening of the basement membrane. The pathogenesis of muscle damage in rheumatoid myositis is discussed. | |
| 3032782 | C1 activation and dissociation in disease. | 1987 Feb | The composition of complexes containing C1 inactivator (C1 IA), C1r and C1s was investigated in normal serum after activation of C1 under various conditions. Analyses were performed with PAGE of eluates from Sepharose beads coated with F(ab')2 fragments of anti C1s followed by immunoblotting with anti C1 IA, anti C1s or anti C1r. Eluates obtained from serum treated with aggregated IgG (AGG) contained C1 IA in complex with C1r and C1s with both subcomponents in activated form. Eluates from serum incubated at 37 degrees C for 1, 2 or 3 days without activators showed C1 IA complexed with activated C1r and with C1s in proenzyme state associated to the complex. On analysis of serum, treated as mentioned above, by a variant of the electroimmunoassay using an intermediate gel containing anti-C1 IA and with anti-C1s in the anodal gel the two types of C1r--C1s--C1 IA complexes could be distinguished. Investigation of fresh sera and synovial fluids from patients with rheumatoid arthritis in this assay showed complexes containing C1 IA and C1r-C1s in activated form in the synovial fluids, while C1 IA-activated C1r-proenzyme C1s complexes were found in the corresponding sera. | |
| 2242065 | Functional studies of soluble low-affinity interleukin-2 receptors in rheumatoid synovial | 1990 Nov | Since abnormal regulation of interleukin-2 (IL-2) has been demonstrated in rheumatoid arthritis (RA), the functional role of low-affinity soluble IL-2 receptors (sIL-2R) purified from RA synovial fluids (SF) was studied. Picomolar levels of sIL-2R were detected in RA SF using an enzyme-linked immunosorbent assay. Levels were higher in serum and SF from RA patients than in controls (P less than 0.001) and higher in RA SF than in paired RA serum (P less than 0.01). Soluble IL-2R from RA SF had estimated molecular weights of 40-50 kd and 80-100 kd by gel filtration analysis. The 80-100-kd peak is likely to be a dimer of the 40-50-kd peak, since a single 45-kd peak was found after elution from sodium dodecyl sulfate-polyacrylamide gels. Since inhibitory activity for lymphocyte proliferation was found in the 80-100-kd range, the sIL-2R were purified with an anti-CD25 affinity column and further analyzed. The purified fractions did not interfere with the proliferation of mitogen-stimulated lymphocytes or with the binding of radiolabeled IL-2 to CTLL-2 cells, although direct binding of IL-2 was demonstrated. The affinity of sIL-2R from RA SF for binding IL-2 was in the range of 25 nM, which is similar to the affinity of sIL-2R purified from a human T cell clone, indicating that both sIL-2R are low-affinity receptors for IL-2. We conclude that the concentration and binding affinity of low-affinity sIL-2R purified from RA SF render them unable to interfere with IL-2-related activities. | |
| 2505779 | Which traditional measures should be used in rheumatoid arthritis clinical trials? | 1989 Sep | It is standard practice to use multiple outcome measures in rheumatoid arthritis (RA) clinical trials. Because of this, multiple testing is usually done, and there is confusion in the interpretation of the results. It is not clear which measures are the most sensitive to detecting improvement and which provide independent information. To address these questions, we conducted an analysis of pooled raw data from 3 placebo-controlled RA trials: one of methotrexate, another of oral and injectable gold, and the third of low-dose and high-dose D-penicillamine. The results show that the joint tenderness count, erythrocyte sedimentation rate, grip strength, and physician assessment of disease activity perform best in RA clinical trials and cover the domain of change measured by traditional outcome measures. Other clinical measures may provide little additional useful information for a standard therapeutic trial of up to 6 months duration, and some measures, such as the proximal interphalangeal joint circumference, hemoglobin level, and 50-foot walking time, can be eliminated from such trials. | |
| 2073742 | Evidence for locally synthesized and clonally restricted immunoglobulin in the synovial fl | 1990 Dec 13 | In this study, we examined the immunoglobulin (Ig) present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) to determine if it was locally produced and to assess the presence of clonally restricted (oligoclonal) immunoglobulin. We studied SF/serum pairs from 55 RA patients and 23 patients with degenerative joint disease (DJD). We found increases in total protein, IgG, IgA, and IgM in RA vs DJD SF (P less than 0.01). The immunoglobulin present in RA appeared to be locally produced as evidenced by significant increases (P less than 0.01) in the immunoglobulin indices. Regression analysis among the levels of IgG, IgA, and IgM RF and the Ig indices suggested that only a minority of the locally synthesized Ig present was specific for RF. To provide evidence of clonal restriction, we further analyzed the SF specimens by isoelectric focusing and assessed the presence of oligoclonal bands present only in RA SF. In 7/55 RA specimens (13%) we found unique SF IgG bands. All bands were of similar isoelectric point (pI), being quite cathodic with pI greater than 7.5. Our evidence supports synthesis of Ig within RA synovium, with a minority of patients showing prominent and unique SF Ig bands. This suggests an oligoclonal response in SF of some patients, but polyclonal Ig synthesis in most. | |
| 1681633 | [Keratomalacia in rheumatoid arthritis: immunohistologic and enzyme histochemical studies] | 1991 May | Corneal and conjunctival biopsies of 13 patients with rheumatoid arthritis and corneal ulceration (RA-keratomalacia) have been characterized by immunohistological and histochemical analysis. Biopsies from 13 patients with bacterial conjunctivitis, 7 patients with allergic conjunctivitis, 15 patients with senile cataract and 15 patients with keratokonus served as controls. The phenotypic composition of the conjunctival inflammatory infiltration of rheumatoid corneal ulceration was not significantly different from the other inflammatory eye diseases studied. However, conjunctival epithelial cells of all RA-patients showed strong de novo expression of HLA-DR- and DP-antigens. HLA-DQ-antigens were only weakly expressed in a minority of patients. In bacterial conjunctivitis a less intense HLA-class-II-expression was found to be restricted to HLA-DR-antigens. Furthermore, in RA patients stromal fibroblasts of the cornea expressed lysosomal elastase. Both observations could be explained by paracrine action of interleukins produced by infiltrating T-lymphocytes and macrophages. Thus, it might be tempting to speculate that immunologically induced, elastase mediated autodegradation of corneal stroma may be an important factor in the pathogenesis of rheumatoid corneal ulceration. | |
| 2847153 | Presence of antibodies to ubiquitin during the autoimmune response associated with systemi | 1988 Nov | Sera from patients with systemic lupus erythematosus (SLE) were shown to react with both ubiquitin and a synthetic fragment of it (residues 22-45) in an ELISA and with ubiquitin in immunoblotting experiments. Close to 80% of lupus patients possessed ubiquitin antibodies, whereas only 55% of them possessed native DNA antibodies, a marker of SLE. Less than 16% of patients with other rheumatic autoimmune diseases possessed antibodies to ubiquitin. Our results indicate that the combined measurement of antibodies to native DNA and to ubiquitin could appreciably increase the detection of SLE cases (up to 85% in our study). It is suggested that ubiquitin, a heat shock protein, could be involved in antibody formation against ubiquitin-protein conjugates present during cellular injury and that this represents a major characteristic of the autoimmune response in SLE. | |
| 2104229 | Polypeptide growth factors augment interleukin 1-induced release of prostaglandin E2 by rh | 1990 Jul | When stimulated with increasing amounts of interleukin 1 beta (IL 1 beta) rheumatoid arthritis (RA), as compared with osteoarthritis (OA), synovial cells grown in RPMI plus fetal bovine serum (FBS), released significantly more prostaglandin E2 (PGE2) (p less than 0.05; paired t test, two-tailed). PGE2 release by IL 1 beta-stimulated RA synovial cells grown for 14 days in serum-free RPMI was significantly less than that released by the same cells grown in medium plus 10% FBS (p less than 0.03; two-tailed). Since these data suggest that growth factors present in FBS may augment the effects of IL 1 beta, experiments were conducted to study the influence of four polypeptide growth factors--transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), on IL 1 beta-induced release of PGE2 by cultured RA synovial cells. Both EGF and bFGF significantly enhanced IL 1 beta-induced release of PGE2 (p less than 0.05; paired t test, one-tailed), while PDGF was synergistic with IL 1 beta, significantly increasing release of PGE2 by these cultured cells (p less than 0.02; two-tailed). No such effect was seen when TGF-beta was added to the culture medium. Taken together, these data lend support to the concept that within the synovial micro-environment small quantities of individual growth factors may potentiate the effects of IL 1 beta to amplify intra-articular inflammation. |