Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 6091234 | Activation of latent collagenase by serum proteinases that interact with immobilized immun | 1984 | It has been previously observed that collagen destruction occurs in the vicinity of immune complexes present in articular cartilages of patients with rheumatoid arthritis. When IgG is covalently linked to Sepharose it behaves as if it has reacted with an antigen to form an immune complex, in that it binds the complement component C1 from human serum. Other serum components also interact with this matrix, though their interaction may not be specific for IgG. Two of these components were shown to possess proteolytic activity, one being kallikrein and the other having the properties of plasmin. Both of the activities could activate latent human collagenase. Whilst the binding of the plasmin activity is probably nonspecific, the binding of the kallikrein activity may be selective for IgG (although it is not certain whether this binding is direct or indirect via another molecule). These results therefore suggest that active proteinases such as plasma kallikrein may be selectively concentrated on immune complexes in vivo, where they may locally activate latent proteinases such as collagenase thereby initiating tissue destruction. | |
| 6343491 | An enzyme-linked immunosorbent assay for antistriational antibodies associated with myasth | 1983 May 13 | Autoantibodies to the striations of skeletal muscle (AStrA) detected by immunofluorescence are useful in the diagnosis of a thymoma associated with myasthenia gravis (MG). With the intention of developing a better method, an enzyme-linked immunosorbent assay (ELISA) has been evaluated in 147 MG patients and 200 healthy controls. An additional 107 patients with various autoimmune diseases and autoantibodies were also tested. With a crude actomyosin preparation, the ELISA gave similar results to immunofluorescence, viz. positives in 42% of MG patients, but in all with a histologically proven thymoma. Less than 1% of the healthy controls were positive but false positives were found in patients with liver disease and anti-smooth muscle antibodies. After treatment of rheumatoid arthritis with D-penicillamine the titre of AStrA may rise. The ELISA was shown to be sensitive and reproducible, but immunofluorescence is a more practical method of distinguishing between the different categories of anti-muscle antibodies. ELISA should prove particularly useful for quantitation and sequential monitoring. | |
| 770131 | Clinical use of immunosuppressive drugs: part I. | 1976 | While immunosuppressive drugs are principally used in the treatment of malignant disease, their use in non-malignant disease and transplantation has become commonplace. The mechanisms of action of immunosuppressive agents differ. Alkylating agents react with nucleophilic centres of D, and rna. Folic acid antagonists prevnt the conversion of dihydrofolic acid to tetrahydrofolic acid. Antibiotics act in a variety of different ways; the alkaloids cause metaphase arrest. Cytarabine (cytosine arabinoside), methotrexate, hydroxyurea and thioguanine act during mitosis and the latter also acts during replication is not known... | |
| 92379 | A nephelometric study of the reaction of monoclonal rheumatoid factor with heat aggregated | 1979 Sep | Monoclonal rheumatoid factors (MCRF) have previously been used in a variety of assays for the detection of IgG-containing circulating immune complexes. We have isolated a MCRF from a patient with a lymphoproliferative disorder and have used a nephelometric technique to characterize its reaction with heat-aggreagated gammaglobulin (HAGG) used as a source of artificial immune complexes. The method is simple, economical and rapid and will detect as little as 6 microgram/ml of HAGG over a wide range of physicochemical conditions. A clinical study demonstrated that the sera from thirty-five out of fifty-eight patients (59%) with rheumatoid arthritis and twenty-one out of seventy-four patients (28%) with systemic lupus erythematosus (SLE) gave increased precipitation with MCRF compared with 232 blood donors. However, in marked contrast to previous studies, sucrose gradient ultracentrifugal analysis of nine strongly precipitating sera revealed that in eight the MCRF precipitated with material sedimenting in the monomeric IgG position. In only one specimen did the MCRF react with material sedimenting in heavier regions. It is suggested that different MCRFs vary in the specificity for binding IgG complexes and these reagents should be carefully characterized before becoming established in nephelometric assays for circulating immune complexes. | |
| 7390618 | Enhancement of lymphocyte response to PHA by lysosomal enzymes from polymorphonuclear leuk | 1980 Jun | The effect of polymorphonuclear leukocyte (PMN) granule lysates obtained from joint fluid of RA on the in vitro DNA synthesis of PHA-stimulated autologous lymphocytes from joint fluid was studied. Lymphocytes were cultured for 3 days with or without PMN lysates in 2 ml of RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum (FCS). The lymphocytes were stimulated with phytohemagglutinin (PHA-M). The DNA synthesis was measured by counting the [3H]thymidine incorporation. Lymphocytes from RA joint fluid stimulated with PHA-M showed 19,466+/-987 cpm (mean+/-SE) per 10(6) cells in the absence of PMN lysates. Upon addition PMN lysates to the PHA-stimulated lymphocytes, the maximum in vitro DNA synthesis increased to 44,877+/-1338 cpm. The enhancing effect of PMN lysates was abolished by plasma inhibitors or by passage through a column of protease inhibitor (Trasylol). It was concluded, therefore, that the enhancing effect of PMN lysates on PHA-stimulated lymphocytes may be associated with lysosomal proteases. Based on experiments using separated T and B lymphocytes, the enhancing effect of PMN lysates was considered to result from the activation of T lymphocytes. The results obtained in the present study suggest an important role for lysosomal proteases in the perpetuation of rheumatoid synovitis. | |
| 461174 | [Acute agranulocytosis after treatment by levamisole. 2 cases (author's transl)]. | 1979 Feb 17 | We describe two patients who had a typical levamisole-induced agranulocytosis and a severe infection; the view of other cases found in the literature shows a fundamental fact: the complication can occur after a variable time of prescription (from thirteen days to eleven months), continuous or intermittent. The accidents are imprevisible, and circonspection must be used, not for its antihelminthic properties, but for its prolonged use for immunological purposes, even if some authors have not observed any cases of agranulocytosis in large series. Naturally, the purpose is quite different in the case of a severe rheumatoid arthritis or inesthetic warts, and our two observations are very demonstrative. Mechanism of agranulocytosis has not been totaly clarified: we have observed biological stigmates of immunological process against levamisole (responsible of agranulocytosis?), but essentially medullary lesions (successive regenerative aspects and necrosis) as has been described with pyramidon, and this could explain why the other blood cells are affected in an apparently isolated agranulocytosis. | |
| 804868 | Influence of tubercle aggregate size on severity of adjuvant arthritis in the rat. | 1975 Feb | Incorporation into Freund's complete adjuvant of tuberculous aggregates smaller than 90 mum in size is essential to produce adjuvant arthritis in the rat, and this correlates with a significantly greater degree of cell-mediated immunity to tuberculous antigens produced by small aggregates (smaller than 90 mum), when compared with large (larger than 90 mum) aggregates. This requirement for small aggregates to render Freund's complete adjuvant arthritogenic is not paralleled by detectable differences in antimycobacterial humoral antibody production nor by a size-dependent requirement for a conventional adjuvant effect. | |
| 109914 | Gold and thiol compounds in the treatment of rheumatoid arthritis: excretory fate and tiss | 1979 | Double isotope-labelled auro thiomalate (Au195-C14-thiomalate) has been administered to mice and rats, and the excretory fate and tissue distribution have been studied. The results show that the gold and the thiomalate separate in vivo resulting in protein-bound gold and release of free thiomalate. About half of this thiol is excreted in the urine during the first day and the remaining half is taken up by the tissues. Thiomalate penetrates cellular membranes poorly, but is able to interact slowly with proteins (mixed disulphide formation). Part of the thiomalate which remains in the body is membrane bound. In contrast to penicillamine little thiomalate remains in circulation a few hours after administration. Gas chromatography--mass spectrometry has been used to search for the presence of free thiomalate in rheumatoid arthritis patients on Myocrisin (auro thiomalate) therapy. Thiomalate was found in their urine, but not in serum and synovial fluid 20 hours after administration. As thiomalate is released in the body after administration of Myocrisin. the question arises whether this thiol, like penicillamine, may have a beneficial effect in the treatment of rheumatoid arthritis. | |
| 6622347 | Kingella kingae causing septic arthritis in Felty's syndrome. | 1983 Aug | A case of septic arthritis of the elbow caused by Kingella kingae, a Gram-negative bacillus, is described. The patient had long-standing, severe rheumatoid arthritis and Felty's syndrome. This appears to be the first report from the United Kingdom of Kingella kingae as the aetiological agent of septic arthritis. | |
| 6393426 | No demonstrable association between HLA DR4 and in vitro collagen reactivity as determined | 1984 Sep | Eight HLA DR4 positive and 9 HLA DR4 negative healthy volunteers as well as 2 DR4 positive and 1 DR4 negative patients with rheumatoid arthritis (RA) were compared for leukocyte inhibition factor (LIF) production and lymphocyte proliferation in response to native and denatured collagen types II and I/III. Purified protein derivative (PPD) of tuberculin served as a positive control in the LIF assay and PPD and phytohaemagglutinin (PHA) in the lymphocyte proliferation test. No significant difference in responsiveness to collagen was detected between these two HLA groups. The reactivity to collagen was not affected by removal of OKT8+ lymphocytes. The present results are in conflict with earlier reports by Solinger et al. (1981) and Solinger & Stobo (1982). The reason for the discrepancy has not been resolved. | |
| 1087595 | Lymphocyte response to IgG in patients with ankylosing spondylitis and their families. | 1976 Dec | Lymphocyte responsiveness to IgG was measured by an agarose method in nine patients with ankylosing spondylitis (AS), one patient with Reiter's Syndrome (RS), and thirty-six of their family members. Similar studies were also performed in five patients with rheumatoid arthritis (RA) and twenty-nine of their first degree relatives as well as in seven control families (twenty-seven subjects). Lymphocytes from the ten spondylitic patients and twenty-four of thirty-six family members responded in vitro to autologous IgG. Although most of these subjects had the histocompatibility antigen, B27, there was no association between B27 and response to IgG. Four of the five patients with RA and twenty of their twenty-nine first degree relatives responded in vitro to IgG, whereas only six of twenty-seven control family members gave a positive reaction. There was no difference in the incidence of antiglobulins (detected by agglutination tests) in the family members of patients with AS and RA or in control family members. These data indicate that lymphocyte responsiveness to IgG is the only aberrant immune response thus far described which is shared by patients with AS and RA and their family members. | |
| 6366990 | The tissue architecture of synovial membranes in inflammatory and non-inflammatory joint d | 1983 | Utilizing monoclonal reagents directed towards antigens of the monocyte-macrophage lineage and Ia antigens, the tissue architecture of synovial membranes obtained from patients with non-inflammatory joint diseases and patients with rheumatoid arthritis was studied. Emphasis was placed on the localization of the type I, type II and type III synoviocytes that previously had been defined by their cell surface phenotype with regard to the expression of monocyte-macrophage lineage (M theta) and Ia antigens as well as by their phagocytic capacity or the ability to produce glycosaminoglycans. In patients with non-inflammatory joint diseases, cells with the M theta + Ia+ (type I) phenotype constituted the majority of synoviocytes immediately adjacent to the joint cavity; cells with this phenotype were also scattered in the subsynovial tissue and in the perivascular regions. The fibroblastoid type III cells defined by the absence of both M theta and Ia antigens formed the major cell population in the subsynovial tissue in this patient group. In patients with rheumatoid arthritis, the Ia+ M theta + cells were present in a characteristic double configuration forming an intensely positive layer adjacent to the intra-articular space followed by an Ia- M theta - layer that again was succeeded by an intensely Ia+ M theta + layer. Large numbers of synoviocytes bearing M theta + Ia+ antigens were also demonstrated in the diffusely inflamed subsynovial tissue, in the perivascular regions as well as around and within lymphoid infiltrates.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 313859 | The significance of antibodies to poly(adenosine diphosphate-ribose) in systemic lupus ery | 1979 Apr | Poly(adenosine diphosphate-ribose) and ds-DNA binding activity have been measured in thirty-nine systemic lupus erythematosus (SLE) sera, nineteen rheumatoid arthritis sera, fourteen sera from non-SLE rheumatic and non-rheumatic diseases and in ten normal sera. Antibodies to poly(ADP-ribose) were found only in the SLE and in three SLE-like rheumatic diseases. Anti-DNA antibodies, on the other hand, were found not only in the SLE and SLE-like diseases, but also in rheumatoid arthritis and chronic active hepatitis. Estimation of poly(ADP-ribose) binding was, therefore, more specific for, and more discriminatory of SLE from other diseases, than the estimation of ds-DNA binding. The results indicate that the estimation of poly(ADP-ribose) binding in serum may be more useful in the diagnosis of SLE than the presently employed estimation of DNA binding using the Amersham kit. DNA-anti-DNA immune complexes are detected in some of the SLE sera after deoxyribonuclease I digestion, confirming earlier reports of the existence of circulating DNA-anti-DNA complexes in SLE patients. Snake venom phosphodiesterase treatment of some of the SLE sera also resulted in increased poly(ADP-ribose) binding activity, suggesting the existence of poly(ADP-ribose)-anti-poly(ADP-ribose) immune complexes in the circulation of SLE patients. This observation raises the possiblity that poly(ADP-ribose) immune complexes may play some part in the pathogenesis of some cases of SLE. | |
| 315610 | [Antinuclear antibodies: immunological characteristics and clinical significance]. | 1979 Jun | Fifty sera containing antinucleolar antibodies were o gathered in a routine laboratory during testing for antinuclear antibodies with indirect immun-fluorescence over a five-year period. The patients involved were suffering from sclerodermia (13 cases), rheumatoid arthritis (7 cases), polymyositis (3 cases), lupus (2 cases), various rhumatismal disease (59 cases) and non rhumatismal diseases in 16 cases, including 5 malignant diseases. In 80 per cent of the cases nucleolar fluorescence was combined with nuclear fluorescence of another type. The antibodies were almost always of the IgG category and belonged in 2/3 of cases to several immunoglobulin categories, most often IgG-IgA. Pretreatment of the liver cuttings with RNase always modifies the nucleolar fluorescence, most often making it negative, and pretreatment with DNase using a combination of enzymes 10 times higher also modifies it (more often decreasing it than making it negative), which indicates that the nucleolar antigen, probably an ARN with a low molecular weight, also depends upon the ADN. | |
| 266593 | HLA B27 and ankylosing spondylitis in the Israeli population. | 1977 | The distribution of 24 HLA antigens of the A and B loci was investigated in 38 Israeli ankylosing spondylitis (AS) patients of various ethnic origins. This was compared with the distribution in rheumatoid arthritis (RA) and osteoarthritis (OA), as well as in 456 controls representing the Jewish population and 260 controls representing the Arab population. Included in the study were Ashkenazi Jews and non-Ashkenazi Jews, as well as Moslem and Christian Arabs. The frequency of HLA B27 among AS patients (79 per cent) was significantly greater (P less than 10(-10)) than among the controls (three per cent). Ashkenazi Jews showed a higher relative risk than non-Ashkenazi Jews and Arabs. Six of the AS patients were offspring of consanguineous marriages, but this was not higher than expected and therefore no indication for rare recessive genes contributing to the disease could be demonstrated. This study confirms the association between AS and B27, and extends our knowledge to the heterogeneous population of Israel not previously investigated. A significant but weak association of B27 with RA was noted. No correlation of other HLA antigens with RA or OA was observed. | |
| 6408886 | Diffuse pulmonary injury associated with gold treatment. | 1983 Jul | A patient showing a gold-induced diffuse pulmonary reaction is described. An open lung biopsy specimen showed thickening of alveolar septa due to inflammation. The alveolar walls were lined by cuboidal epithelium. On electron microscope examination electron-dense structures were observed within lysosomes of endothelial cells of the alveolar capillaries and interstitial macrophages. Electron probe microanalysis showed that these structures contained gold. The accumulation of gold in endothelial cells and macrophages and a direct toxic effect might be an important feature in the pathogenesis of gold-induced pulmonary reactions. On the other hand the accumulation of gold may reflect exposure rather than disease. | |
| 7239398 | [Therapy of gastrointestinal disorders due to oral rheumatism therapy. Effect of bromoprid | 1981 May 21 | Non-steroid antirheumatic agents inhibit the synthesis of prostaglandins to an extent which depends upon their respective chemical composition. The result of this inhibition is a reduction in gastric mucosal perfusion, a limitation of cytoprotective factors, and an enhanced back diffusion of H+-ions into the mucosal cell. The function of the gastric mucosal barrier is restricted and a reduction in the measurable electric potential between the gastric serosa and mucosa ensues. Adjunctive therapy with bromopride (Cascapride) improves this reduction in gastric potential difference induced by the antirheumatic agent, and alleviates the gastrointestinal symptoms brought on by the antirheumatic drug. | |
| 6983116 | Increased number of IgG Fc receptors on monocyte-enriched peripheral blood leucocytes from | 1982 Oct | The number of free Fc receptors (FcR) per cell and the association constant (Kass) for the binding of monomeric IgG were determined for monocyte-enriched peripheral blood mononuclear cells, isolated from 16 patients with active classical rheumatoid arthritis (RA) and from 15 normal healthy donors. The assay system was based on binding under equilibrium conditions of 125I-labelled monomeric rabbit IgG to monocytes purified from peripheral blood on a continuous gradient of Percoll. Monocytes from 14 untreated RA patients (6 seropositive, 8 seronegative) expressed on the average 4.8 +/- 1.3 x 10(4) FcR/cell. This number was significantly higher (P less than 0.001) than that found in the control group (34. +/- 0.7 x 10(4) FcR/cell). There was also a significant difference between the mean Kass of the RA group and the control group--2.1 +/- 0.7 x 10(8) l/mol and 2.6 +/- 1.0 x 10(8) l/mol, respectively (0.05 greater than P greater than 0.01). Two seropositive RA patients receiving systemic treatment with penicillamine expressed the same number of FcR/cell as the mean of the control group (3.6 x 10(4)). Levels of circulating immune complexes (CIC) and the complement-factor C3 split product C3d were also measured. No correlation was found between the number of FcR/cell and the concentration of C3d, but there was a weak correlation between the number of FcR/cell and the level of CIC. | |
| 7240722 | Biochemical and immunological studies of lysosomal and related proteinases in health and d | 1981 Mar | A review of continuing studies on the physiological and pathological roles of the lysosomal proteinases, cathepsin D and cathepsin B is presented. Intracellular release of cathepsin D from lysosomes has been demonstrated during myocardial ischemia. Both this proteinase and cathepsin B have been found, by organ culture in the presence of the appropriate antiserum, to be released into the extracellular space in rheumatoid synovium, where they may play a part in cartilage destruction. Also reviewed is the finding of a cathepsin B-like proteinase that, in organ culture, is secreted in markedly increased amounts from human malignant breast carcinomas in comparison to amounts secreted from benign tumors or normal tissue. | |
| 6819847 | Gold induced enterocolitis: case report and a review of the literature. | 1982 Dec | The use of gold therapy in rheumatoid arthritis is not without risk. Although the better known side effects are bone marrow suppression and renal involvement, gold induced enterocolitis has been described. This paper reports a 59-year-old female recently treated with gold therapy for rheumatoid arthritis who developed bloody diarrhoea, toxic dilatation and perforation of her colon. The absence of features of inflammatory bowel disease or infection indicates gold as a possible causative agent. Pathogenesis, therapy and a review of the literature of gold induced enterocolitis are described. |