Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
2084232 Antibody to interleukin 1 inhibits the cartilage degradative and thymocyte proliferative a 1990 Dec Cartilage breakdown in rheumatoid arthritis results from (a) lytic action by synovial enzymes, and (b) release of synovial catabolin, now believed to be a form of interleukin 1 (IL-1), causing chondrocytes to degrade their matrix. Rheumatoid synovial culture media were tested for their ability to stimulate cartilage degradation (proteoglycan release from bovine nasal cartilage discs) and thymocyte proliferation (3H-thymidine incorporation) in the absence or presence of anti-IL-1. Degradation of living cartilage, stimulated 2-fold by synovial culture media, was inhibited up to 80% by anti-IL-1. Residual breakdown in living cartilage and synovial culture media induced breakdown in dead cultures were of similar magnitude, and both were unaffected by antibody treatment. Proteoglycan products released from synovial culture media treated cartilage were of smaller average molecular weight (Sepharose CL-2B), and such size reduction was inhibited by anti-IL-1 treatment. Synovial culture media that stimulated cartilage degradation also stimulated thymocyte proliferation; the latter was fully suppressible by anti-IL-1. One of 8 synovial culture media contained an inhibitor(s) of thymocyte proliferation, removable by dialysis. We conclude (1) rheumatoid synovial catabolin activity is due to a form of IL-1. (2) A minor nonsuppressible component of synovial culture media stimulated breakdown, identical in living and killed cartilage, is due to passive transfer of enzymic activity. (3) Cultured rheumatoid synovium releases both IL-1 and an inhibitor(s) of IL-1 action.
3075080 The significance of CD5+ B cells in rheumatic diseases. 1988 The presence of autoantibodies in rheumatoid arthritis (RA) and primary Sjögren' syndrome (SS) is a feature of these diseases. Because of the probable role of autoantibodies in the pathogenesis of RA and primary SS, the study of the origin and regulation of B lymphocytes producing autoantibodies is of special importance. In mice, B lymphocytes can be divided into two populations of distinct lineages, the conventional bone marrow-derived B subset and the self-renewing peripheral subset. B lymphocytes of the latter express an antigen initially described as T cell specific, the Ly-1 or CD5 antigen. In human, such CD5+B cells are found in foetal lymphoid tissue but their frequency diminishes in adult life. We have found a significant increase in CD5+B cells in the peripheral blood of patients with RA and primary SS, and a small family study of relatives of two RA patients suggests that such 'high phenotype' could be a genetic trait. Furthermore, CD5+B cells appear enriched in autoantibody-producing cells since they produce IgM-rheumatoid and other autoantibodies when suitably activated in vitro. Our current hypothesis is that persistence of high numbers of CD5+B cells in adulthood may predispose to chronic inflammatory arthritis due to the reactivity of the antigen receptor of these cells with a variety of autoantigens in the joint. Such reactivity would allow an autoimmune reactions causing the perpetuation of chronic inflammation at the disease site.
2269160 [Clinical study on rheumatoid arthritis of the TMJ]. 1990 Jul 256 individuals with inflammatory rheumatic diseases and 117 individuals of two control groups returned their questionnaires in a survey of subjective symptoms of the masticatory system. Subjective symptoms of the temporomandibular joint (tmj) were reported by 41% of the patients with rheumatoid arthritis, 29% of the patients with psoriatic arthritis, 20% of the patients with ankylosing spondylitis and 23% of the patients with other rheumatic diseases (such as Reiter's syndrome). Statistically significant differences (p less than 0.05) regarding the occurrence of "difficulties in opening the mouth wide" and "crepitus from the tmj" were found between the various types of rheumatic arthritis. In 40 patients with rheumatic diseases and tmj-symptoms the tmj was examined clinically, by orthopantomography and lateral tomography. Radiographic abnormalities were found in 68% of the patients and classified by a new radiographic index, according to the index of Steinbrocker. There were no indications for a relationship between a loss of posterior support and extensive radiographic changes of the tmj. The most common objective symptoms were pain on chewing, crepitus in the tmj and tenderness to palpation of the masticatory muscles and neck.
2501852 [Comparative evaluation of the effectiveness of gold preparations and D-penicillamine and 1989 Jan In the period of 5 years the authors observed 213 patients with RA. Of this number 80 patients got Au parenteral preparations and 61--D-penicillamin in the average daily dose of 450 mg. The efficacy of the drugs was assessed by its effect of the indices of the activity (quantitative assessment of clinical manifestations of vascular syndrome) which had been determined by the time of treatment and on the 3, 6, 12, and 18th month of subsequent therapy.
2457523 An observer-blind crossover study to compare the efficacies of flurbiprofen, indomethacin 1988 May An observer-blind three-period crossover study of flurbiprofen, indomethacin and naproxen was carried out in 56 patients with rheumatoid arthritis. The drugs were scheduled as two oral doses early in the day with a rectal suppository at night. The aims were to compare efficacy, principally as relief of night pain and morning stiffness, and safety. Flurbiprofen was clearly the most beneficial drug. Advantages over the comparators were demonstrated in terms of shorter duration of morning stiffness, reduced severity of night pain (compared with naproxen) and in the improvement in sleep quality experienced by the patients. Excellent tolerability of flurbiprofen was seen, it being equivalent to naproxen and superior to indomethacin. The results demonstrate that nocturnal and early daytime provision of flurbiprofen is a highly effective strategy for controlling the nocturnal pain and morning stiffness of rheumatoid arthritis.
2966579 Abnormalities in CD4+ T-lymphocyte subsets in inflammatory rheumatic diseases. 1988 May The monoclonal antibodies anti-2H4 and anti-4B4 identify the suppressor-inducer (CD4+2H4+) and helper-inducer (CD4+4B4+) subpopulations of CD4 (T4+) lymphocytes, respectively. The cell surface phenotype of peripheral blood lymphocytes and synovial fluid lymphocytes in patients with rheumatoid arthritis and other inflammatory joint diseases was analyzed by use of these and other well-characterized anti-T-cell monoclonal antibodies. In the synovial fluid of patients with rheumatoid arthritis, there was a markedly decreased percentage of T4+2H4+ suppressor-inducer cells (3.1 +/- 1 percent) and an increased percentage of T4+4B4+ helper-inducer cells (29.1 +/- 9 percent) as compared with the proportions found in the peripheral blood of normal individuals (T4+2H4+: 19.0 +/- 6 percent, T4+4B4+: 23.0 +/- 7 percent). Moreover, patients with other chronic and acute inflammatory joint diseases exhibited highly similar synovial T-cell findings to those of the patients with rheumatoid arthritis (T4+2H4+: 4.2 +/- 3 percent, T4+4B4+: 33.1 +/- 9 percent). In contrast, there were no significant differences between the normal control subjects and patients with rheumatoid arthritis in the percentage of T4+2H4+ cells in peripheral blood lymphocytes, nor were there significant differences between normal control subjects, patients with rheumatoid arthritis, and patients with other joint diseases (osteoarthritis, gout, B27+ spondyloarthropathy, and psoriatic arthritis) in the number of T4+4B4+ cells or in the T4/T8 ratio of peripheral blood lymphocytes. However, very low numbers of T4+2H4+ (suppressor-inducer) peripheral blood lymphocytes were seen in a subgroup of patients, including five of seven with Reiter's syndrome and several patients with systemic rheumatic disease syndromes. In addition, although the percentage of T4+2H4+ cells in peripheral blood lymphocytes of patients with osteoarthritis (13.7 +/- 7 percent) and gout (14.3 +/- 7 percent) was decreased compared with that of normal controls (19.0 +/- 6 percent) (osteoarthritis versus normal controls p less than 0.025), this difference appeared to reflect alterations due to age rather than disease. Consistent with the phenotypic changes observed, synovial T cells were also functionally defective, since autologous mixed lymphocyte reaction-activated T4 cells from the synovial fluid of patients with rheumatoid arthritis failed to exhibit suppressor-inducer activity.(ABSTRACT TRUNCATED AT 400 WORDS)
3673142 [The primary inflamed and primary degeneratively changed joint from the viewpoint of physi 1987 Aug 1 The author emphasizes the interdisciplinary approach that is necessary to rheumatic arthropathies. The pain, inflammation and disturbance of movement must be seen as requiring physiotherapy, while a degree of differentiation is necessary in thermotherapy.
3330699 Analysis of the HLA association with rheumatoid arthritis. 1986 Jun Definitive determination of the HLA linked gene or genes for susceptibility to RA will be achieved (1) by the accumulation of an adequate body of data on the haplotype frequencies in a random set of RA patients and controls and (2) by further study of other loci in the DR region, involving the use of DNA probes as well as conventional techniques. Indirect evidence is here put forward to suggest that it may turn out that some part of DR4 specificity itself may be directly involved in increasing susceptibility and that DR1 epitopes may be involved in a similar way.
3394092 [Characteristics of keratoconjunctivitis sicca in Sjögren's disease and syndrome]. 1988 The paper is devoted to an analysis of the clinical manifestations of keratoconjunctivitis sicca in Sjogren's syndrome in combination with SLE, sclerodermia systematica, rheumatoid arthritis, and in Sjogren's disease. Some characteristic signs of a course of keratoconjunctivitis sicca in Sjogren's disease and syndrome were defined.
2547713 Effect of piroxicam therapy on granulocyte function and granulocyte elastase concentration 1989 Apr The effect of piroxicam therapy (20 mg/day for 15 days) on various polymorphonuclear granulocyte (PMN) responses and on PMN elastase concentration was investigated in nine patients with active rheumatoid arthritis. Peripheral blood and synovial fluid samples were collected before starting therapy and 12 h after the last dose of the drug. All patients were evaluable for peripheral blood analysis and six for synovial fluid analysis. Piroxicam therapy had no effect on PMN random migration and phagocytosis, while it significantly reduced both FMLP-induced aggregation and FMLP-induced chemotaxis. This seems mainly due to an effect on FMLP binding, as no differences were observed after therapy in PMA- and PHA-induced aggregation as well as in serum-induced chemotaxis. In contrast, a marked impairment of NBT test and PMA- and FMLP-induced superoxide anion (O2-) production was found after piroxicam therapy. This effect was as evident in peripheral blood as in synovial fluid PMN. Also, a significant reduction in synovial fluid PMN number and synovial fluid PMN elastase concentration (elastase-alpha 1-proteinase complex) was found after treatment. It is concluded that piroxicam may act at different sites on various PMN responses. Its effect on O2- generation and PMN elastase concentration in synovial fluid may have an important role in reducing destruction of arthritic joint tissue.
3768055 Intraarticular ferritin-bound iron in rheumatoid arthritis. A factor that increases oxygen 1986 Oct Iron mobilized from ferritin is able to convert superoxide and hydrogen peroxide, which are produced in large amounts in rheumatoid arthritis (RA), to the extremely toxic hydroxyl radical. We have found that synovial fluid ferritin is increased significantly in RA patients compared with levels in controls. The high synovial fluid:serum ferritin ratio is compatible with the hypothesis that synovial fluid ferritin is derived from the synovial membrane. We found no difference in ferritin concentrations in the synovial membranes of RA patients compared with those of controls. Quantitative data on the amount of iron bound to ferritin showed that the level was 2.9 times higher in RA synovial membranes than in those of controls. Moreover, RA synovial fluid contained considerable amounts of iron bound to ferritin. Calculation of the iron saturation of ferritin revealed that RA synovial membranes contained a mean of 2,210 moles of iron per mole of ferritin: a significant elevation when compared with the mean value of 1,500 moles found in the synovial membranes of the controls. The decreased saturation of ferritin in RA synovial fluid, compared with that in the synovial membrane, could be caused by an uncompensated release of iron from ferritin, which has been induced by superoxide that is produced by stimulated granulocytes. The results demonstrate that in the joints of RA patients, sufficient ferritin loaded with iron is available to stimulate oxygen free radical damage.
2789500 Serum osteocalcin concentrations in patients with rheumatoid arthritis. 1989 Aug Osteocalcin is a non-collagenous bone matrix protein which is released into the circulation and can be measured by radioimmunoassay. Recent studies indicate that serum osteocalcin concentrations are a marker of bone formation. Because bone demineralisation is a common finding in patients with rheumatoid arthritis (RA) the serum osteocalcin concentrations and, in addition, the serum concentrations of 25-hydroxyvitamin D, parathyroid hormone, and calcitonin were measured in 29 patients with RA and in 30 control subjects. Whereas serum osteocalcin concentrations were similar in patients with RA and in control subjects, serum 25-hydroxyvitamin D concentrations were significantly decreased in patients with RA. Serum concentrations of parathyroid hormone and calcitonin in patients with RA and in control subjects were not statistically different. The normal osteocalcin concentrations in patients with RA suggest a normal rate of bone formation in these patients.
2396864 Cytidine deaminase activity in synovial fluid of patients with rheumatoid arthritis: relat 1990 Aug It is claimed that cytidine deaminase activity reflects local granulocyte turnover or activity in the synovial fluid of patients with rheumatoid arthritis, but cytidine deaminase is not a granulocyte specific enzyme. Lactoferrin is a granulocyte specific protein that is released from the secondary granulae during activation. We measured cytidine deaminase activity and lactoferrin concentrations in 33 rheumatic synovial fluid samples. Cytidine deaminase activity and lactoferrin concentrations correlated closely, indicating that both analyses reflect similar events in the joint-that is, result in their release from granulocytes. Cytidine deaminase activity and granulocyte concentrations correlated less closely, suggesting that there are additional factors besides the cell number which contribute to this release. Joint acidosis may be one such factor, as pH and cytidine deaminase activity correlated inversely. There was no association with synovial fluid proteoglycan concentrations, a marker of cartilage degradation.
2013671 Altered T cell subpopulations and lymphocytes expressing natural killer cell phenotypes in 1991 Apr Scleroderma (progressive systemic sclerosis [PSS]) is known to be associated with abnormal T cell immunoregulation. In the present study, we evaluated lymphocyte phenotypes in patients with PSS and normal control subjects by flow cytometry and monoclonal antibodies for total T (CD3), T suppressor (CD8), T helper (CD4), T helper-inducer (CDw29), T suppressor-inducer (CD45R), human leukocyte antigen, DR+B (CD19), DR+T, and natural killer subsets, HNK-1 (CD57) and NKH-1 (CD56) cells. Patients with PSS compared to normal subjects had significantly lower percentages of CD3+ (p less than 0.005) and CD8+ (p less than 0.05) (similar to several patients with rheumatoid arthritis also evaluated), as well as CD45R (p less than 0.05), T+DR+ (p less than 0.05), and NKH-1 (CD56) (p less than 0.0005) cells. Patients with PSS with late-limited or generalized disease had lower percentages of CD8+, CD19, NKH-1+, and CDw29, but higher percentages of CD4+, HNK-1, and CD45R cells compared to patients with early stage disease, but these results were not statistically significant. These unique alterations in patients with PSS may prove to be useful in monitoring the stage of disease activity for therapy and further define immunologic defects.
2525747 [Complications of rheumatoid pericarditis: constriction and tamponade]. 1989 Jun 10 Pericarditis is frequent in patients with rheumatoid arthritis. It is usually asymptomatic, but cases of constrictive pericarditis or, more rarely, tamponade have been reported. In such cases, the study of pericardial fluid is of special interest for the aetiological diagnosis. Early medical treatment with or without pericardiocentesis is effective in most cases of tamponade, but constrictive pericarditis demands pericardiectomy. We report here three cases of pericarditis responsible for cardiac compression: two cases of tamponade and one case of constrictive pericarditis.
2959336 The interstitial lung disease associated with rheumatoid arthritis: evidence for imbalance 1987 May Rheumatoid arthritis (RA) is a generalized disorder characterized by chronic inflammation of peripheral joints and by involvement of many organs, including the lung parenchyma. The inflammatory infiltrates of the rheumatoid synovial membranes are associated with increased numbers of T-lymphocytes, with increased proportions of helper (OKT4 positive) T-cells and decreased percentages of suppressor/cytotoxic (OKT8 positive) T-cells, and since patients with interstitial lung disease associated with RA often have increased numbers of lymphocytes in the alveolar structures, it seemed possible that rheumatoid lung disease could also be associated with an imbalance of T-lymphocyte subpopulations. To test this hypothesis, patients with chronic interstitial lung disease and RA were evaluated by lung biopsy, gallium-67 scanning and bronchoalveolar lavage to assess the activity of the lung disorder and the T-lymphocyte subpopulations were identified with the OKT4, OKT8 and Tec T-5.9 monoclonal antibodies. The Tec T-5.9 is a recently described monoclonal antibody which recognizes a small T-cell fraction of the OKT4 positive T-lymphocytes, responsible for many helper T-cell functions, including the response to allogenic antigens and help in immunoglobulin production by B-cells. Histologic evaluation of the biopsies demonstrated active lung inflammation in all patients and gallium-67 scans showed an increased lung uptake in five of the six patients studied.(ABSTRACT TRUNCATED AT 250 WORDS)
3379619 The prevalence of rheumatoid arthritis in a rural African population. 1988 Mar We report the findings of an epidemiological study of the prevalence of rheumatoid arthritis (RA) in a rural population. The study was conducted in Venda, a very remote part of South Africa. Much of the population still follows an age old traditional lifestyle. A detailed hut-to-hut survey of 543 respondents comprising 97% of the population of one village was conducted. This included clinical, serological and radiological studies. This was supplemented by questioning local traditional doctors and showing them photographs of typical hand deformities to ascertain if they knew of any cases with these deformities. The 3 hospitals draining the area were also surveyed. The detailed survey of 543 respondents revealed no cases of definite or probable RA using a modification of the Rome criteria. No cases were recognized by the traditional doctors. The 3 hospitals together had 14 cases of definite RA out of a population of about 520,000. This gave a prevalence of 0.0026%. The marked difference in the prevalence of RA in this population as opposed to other Southern African studies as well as American and European studies is discussed.
3616445 [Chromosome anomalies in rheumatoid polyarthritis. Breakage level and study of the breakin 1986 Nov This current study confirms the significant elevation of the rate of chromosomal abnormalities (18.32 p. cent in 90.62 p. cent of cases) and the presence of a breaking capacity of the serum in a series of 78 rheumatoid polyarthritis compared with a control group. Chromosomal gaps and breaks represent the most frequently encountered lesions. These lesions are observed from the onset of the disease but are not specific of this disease. Chromosomal abnormalities do not seem to be randomly distributed on the chromosomes. They are not correlated with clinical or biological parameters in a statistically significant fashion. The cytogenetic study only represents a non specific biological test of rheumatoid disease. The advantage could apply, in practice, to beginning or atypical forms of rheumatoid polyarthritis in order to identify them within the group of auto-immune diseases.
1746169 [Panhypogammaglobulinemia: a rare complication of parenteral gold therapy]. 1991 Jul Secondary antibody deficiency is one of the rare adverse effects of chrysotherapy in rheumatoid arthritis. The plasma levels of all immunoglobulins fall into ranges significantly lower than the tolerable physiological minimum. The long-lasting panhypogammaglobulinemia can increase the risk of infection in the patient and, therefore, should be closely monitored. Hence, a record of immunoglobulin levels before and during therapy with gold compounds seems to be mandatory.
3960569 Development of an observation method for assessing pain behavior in rheumatoid arthritis p 1986 Feb Four studies examined the reliability and validity of a behavioral observation method for the assessment of pain associated with rheumatoid arthritis (RA). The major purpose of experiment 1 was to evaluate the interobserver reliability of the observation method. Two observers recorded the frequencies of pain behaviors displayed by 20 RA patients. Each of 3 types of reliability estimates indicated that the pain behavior could be reliably observed. The purpose of experiment 2 was to examine the concurrent validity of the observation system by correlating 53 patients' self-reports of pain with the frequencies of their pain behaviors. Significant and positive correlations were found between patients' total pain behavior and 3 self-report measures of pain and functional disability. Furthermore, unlike the self-reports of pain, total pain behavior was only minimally related to self-report of depression. Experiment 3 was performed in order to assess the observation method's construct validity. Naive observers viewed video recordings of 25 RA patients and made global estimates of patients' pain severity and unpleasantness. Highly significant and positive correlations were found between these global estimates and total pain behavior. In experiment 4, the pain behaviors of 11 RA patients were recorded prior to and immediately following cognitive-behavioral treatment for the reduction of RA pain. There was a significant decrease in total pain behavior from pretreatment to posttreatment. The data indicate that the observation method provides a reliable, valid, and relatively objective measure of RA patient pain behavior. Future validation studies of the observation method are discussed.