Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2375908 | HLA class I expression on erythrocytes and platelets from patients with systemic lupus ery | 1990 May | It has previously been shown, by a haemagglutination assay, that patients with systemic lupus erythematosus (SLE) express increased levels of HLA class I on erythrocytes compared with normal subjects and patients with rheumatoid arthritis (RA). A radioligand-binding assay, using monoclonal antibody W6/32, was devised to quantify HLA class I expression on erythrocytes and platelets. An increased number of class I molecules was expressed on erythrocytes from 45 patients with SLE (mean = 354 molecules per cell, median = 255 molecules, range = 30-1270 molecules per cell), compared with cells from 46 normal subjects (mean = 132, median = 78, range = 40-550) and 31 RA patients (mean = 132, median = 89, range = 26-497). The presence of HLA-B7 correlated with increased class I expression on erythrocytes from both normal subjects and patients with SLE. Levels of HLA class I in serum were measured. All subjects with HLA-A9 (A23, 24) showed higher levels of serum class I than their A9-negative counterparts, and there was no difference in levels between SLE patients and normal subjects. There were no correlations between class I levels in serum and on erythrocytes amongst SLE patients or normal subjects. Red cells were fractionated, according to their age in vivo, on Percoll gradients. Class I levels fell with increasing erythrocyte age in all individuals, but were higher in all fractions from SLE patients compared with age-matched fractions from normal subjects. HLA-B7-positive erythrocytes also expressed higher class I levels in each Percoll fraction, compared with their HLA-B7-negative counterparts, suggesting that enhanced B7 expression is not due to greater structural stability of this class I allotype. These data are compatible with the hypothesis that class I is expressed as an intrinsic protein of erythrocyte membranes and that expression is increased amongst patients with SLE. | |
| 1925397 | [Evans' syndrome caused by D-penicillamine in rheumatoid arthritis. Value of the corticoid | 1991 Jul | The authors report the development of thrombocytopenia purpura in one patient with seropositive and erosive rheumatoid arthritis treated successfully for 11 months with D-penicillamine. Anti-platelet-bound antibodies were present, but also: anti-erythrocyte antibodies with hemolytic anemia (then defining Evans's syndrome): higher level of antinuclear antibodies; intermittent neutropenia. The responsibility of D-penicillamine is discussed, but thrombocytopenia purpura evolved for itself. Glucocorticoids alone, intravenous immunoglobulin, vincristine did not induced remission, which at least occurred under the association danazol-glucocorticoids, without toxicity, especially on the liver function. | |
| 2720963 | Alkaline phosphatase isoenzymes in rheumatic diseases. | 1989 Apr | Serum alkaline phosphatase isoenzymes were determined quantitatively by electrophoresis on cellulose acetate in 168 patients with rheumatic diseases subgrouped for disease activity. Median values of total alkaline phosphatase and bone isoenzyme activity, as well as frequency of patients showing pathological values, increased gradually and significantly corresponding to disease activity in rheumatoid arthritis and ankylosing spondylitis, from 0% in inactive to 90% in very active forms. Bone isoenzyme was much more sensitive than total alkaline phosphatase in moderate disease activity and was also correlated to the number of involved extravertebral joints and pain in ankylosing spondylitis. No correlation was found with stage or duration of disease, age, sex, and erythrocyte sedimentation rate. Additional to bone isoenzyme, liver isoenzymes were elevated in some patients, but with only a weak correlation with disease activity. The intestinal isoenzymes were always normal. We conclude that quantitative determination of serum alkaline phosphatase bone isoenzyme activity is a major indicator for the assessment of disease activity and therapeutic monitoring in rheumatoid arthritis and ankylosing spondylitis. | |
| 3491707 | Enhanced interleukin 1 generation by monocytes in vitro is temporally linked to an early e | 1986 Aug | Twenty-one patients with rheumatoid arthritis (RA) and 12 age and sex matched healthy controls were examined for the ability of their monocytes (adherent cells, AC) to spontaneously secrete interleukin 1 (IL-1) and for their peripheral blood mononuclear cells (PBMC) to secrete interleukin 2 (IL-2) induced by Staphylococcal Protein A (SPA). All RA patients had PBMC which secreted normal amounts of mitogen induced IL-2 regardless of disease activity or disease history. However, AC from RA patients who had a recent (less than 6 months) onset of their disease, or exacerbation of existing RA, had enhanced spontaneous IL-1 secretion. AC from patients with equally active RA but with historically stable disease generated normal amounts of IL-1. Enhanced in vitro IL-1 generation by circulating monocytes is temporally linked to an early event in the onset of exacerbation of RA. | |
| 3175450 | Mononuclear cells recovered from inflammatory synovial membrane using fine-needle biopsy. | 1988 | A simple technique for fine-needle aspiration biopsy from the synovial membrane of arthritis knee joints preceded by lavage of the joint cavity is described. The procedure was atraumatic, well accepted, and could be performed on outpatients. Cells originating from the synovial membrane were obtained in 12 of 17 knees using a 1.2-mm cannula. The yield was 6.0 x 10(3) to 135 x 10(3) mononuclear cells. The cell populations could be expanded by stimulation with antigen and mitogen. The described fine-needle biopsy technique is of value when repeated sampling of synovial membrane cell populations is desired. | |
| 2938530 | The toxicity of D-penicillamine in systemic sclerosis. | 1986 May | We studied D-penicillamine toxicity in 259 patients with systemic sclerosis treated since 1972. The average daily dose of 635 mg was given for a mean of 1.8 years. Of patients with systemic sclerosis, 47% has side effects from D-penicillamine treatment, similar to the 56% of 807 patients with rheumatoid arthritis in seven separate series. Individual manifestations of toxicity included rash, proteinuria, gastrointestinal symptoms, dysgeusia, oral ulcers, thrombocytopenia, and neutropenia. Four episodes each of myasthenia gravis and pemphigus occurred in our patients; both were reported rarely in patients with rheumatoid arthritis. Adverse effects occurred more frequently after rapid increases in dosage. Treatment had to be discontinued due to toxicity in 29% of patients with systemic sclerosis and in 33% of those with rheumatoid arthritis. Although toxic, with a high frequency of adverse effects, D-penicillamine can be used safely in the treatment of systemic sclerosis. Pemphigus and myasthenia gravis may occur more frequently with therapy for systemic sclerosis than with that for rheumatoid arthritis. | |
| 1871515 | [Therapeutic use of a monoclonal, anti-CD4 antibody in refractory rheumatoid polyarthritis | 1991 Jan | Ten patients (6 women and 4 men), with a group mean age of 65 years, defined as severe and with a mean follow-up period of 9 years and refractory to conventional treatments, were treated with monoclonal anti-CD4 antibodies in an open study. The monoclonal antibodies, of murine origin, were administered by intravenous route for ten consecutive days at a dose of 10 mg (1 patient), 15 mg (2 patients) or 20 mg (7 patients). Local and systemic tolerability were excellent. Clinical improvement was rapid (pain, morning stiffness, Ritchie index, p = 0.005 between D0 and D15), as was the paraclinical improvement (C-reacting protein, p = 0.008), although without achieving complete remission. The outcome revealed that the effect was more prolonged in patients treated with 20 mg per day than in the others, suggesting a dose-effect relationship. The improvement obtained may persist for more than 9 months in some patients. No significant change in immunological parameters was found at the end of the treatment (lymphocyte populations, immunoglobulins, complement). Only 2 out of 10 patients developed anti-mouse antibodies. As a result of its excellent tolerability and rapid effectiveness, this antibody appears to offer fresh therapeutic prospects in rheumatoid arthritis. | |
| 3430520 | A family survey of lupus erythematosus. 1. Heritability. | 1987 Oct | First degree relatives and spouses of 36 patients with systemic lupus erythematosus (SLE) and 37 with discoid lupus erythematosus (LE) were assessed using the ARA criteria. They were compared with relatives and spouses of patients with other rheumatic and related complaints. Definite SLE was present in 3.9% of relatives of SLE probands, 2.6% of discoid relatives and 0.3% of controls. Discoid LE was diagnosed in 0.6% of SLE and 3.5% of discoid families compared with 0.5% of controls. None of the spouses of LE probands had SLE or discoid LE. The data gave the best fit for a polygenic inheritance with a heritability of 66 +/- 11% for SLE and 44 +/- 10% for discoid LE. Genetic factors are thus less important in SLE and discoid LE than in generalized osteoarthritis, spondylitis or gout with heritabilities of 90, 72 and 90%, respectively. | |
| 1901258 | Rheumatoid factors and complex formation. The role of light-chain framework sequences and | 1991 Apr | New information regarding rheumatoid factors (RFs) indicates that the RFs synthesized in synovium and lymphoid tissues of patients with rheumatoid arthritis (RA) are different from monoclonal and nonspecific RFs associated with other inflammatory states. The characteristics of RF associated with RA are as follows. They are of all Ig isotypes (not just IgM), indicating T-cell participation in antibody maturation. They have higher avidity for human IgG than for rabbit IgG. They use the human germline heavy-chain variable region (VH) gene VHIII more frequently than other VH genes, and light chains from multiple families. (In contrast, monoclonal RFs use predominantly VH1 and very commonly the V kappa IIIb germline gene HUMkv325). RA IgG is somatically mutated. (In contrast, monoclonal RFs use unmutated germline Ig genes). This suggests they are matured by stimulation either with specific antigens or other activation signals such as cytokines. They are abnormally glycosylated. In general, during periods of disease activity in adult and juvenile RA, a galactose is missing from the Fc of the IgG molecule, leaving an empty "pocket" between the C gamma 2 domains of heavy chains. The IgG RFs self-associate. This may result at least in part when galactose on the F(ab')2 portion of one IgG molecule fills the empty pocket in the Fc of another Ig molecule. Self-association forms immune complexes capable of fixing complement and probably of causing joint damage and vasculitis. | |
| 1748147 | Limiting dilution analysis of proliferative T cell responses to mycobacterial 65-kDa heat- | 1991 Dec | Recent evidence has pointed to the mycobacterial 65-kDa heat-shock protein (hsp 65) as an antigen that may be important in the pathogenesis of rheumatoid arthritis (RA). Using limiting dilution analysis the frequency of purified protein derivative of tuberculin (PPD) and hsp 65-responsive T cells was measured in paired peripheral blood and synovial fluid samples of patients with RA. There was no increase in the anti-PPD or anti-hsp 65 frequency in synovial fluid compared with peripheral blood. In addition, no difference was found between peripheral blood of RA patients and healthy controls. These results do not support the idea of an important pathogenic role of T cells responding to hsp 65, or a cross-reacting antigen, in RA. | |
| 1920943 | [Membranous glomerulonephritis probably related to bucillamine therapy in two patients wit | 1991 Jun | We describe here two patients with rheumatoid arthritis who developed nephrotic syndrome after administration of bucillamine, a novel antirheumatic drug developed in Japan. The nephrotic syndrome occurred after six months' and five months' treatment of bucillamine, respectively. The renal biopsy showed early phase of membranous glomerulonephritis (stage 1) in both patients. The first patient was a 64-year-old man who had received gold therapy for two years, and penicillamine therapy for eight months before bucillamine therapy. The nephrotic syndrome occurred after one year's cessation of the gold therapy and six months' cessation of the penicillamine therapy. The other patient, 57-year-old woman, had no history of gold or penicillamine therapy. Our experience suggests that membranous glomerulonephritis might occur in relation to bucillamine therapy. | |
| 2685982 | Elevated IgG antibody levels to the mycobacterial 65-kDa heat shock protein are characteri | 1989 Nov | We have previously demonstrated raised levels of IgG and IgA antibody to the mycobacterial 65-kDa heat shock protein (hsp) in the sera of patients with rheumatoid arthritis (RA). We have now attempted to determine whether this phenomenon is specific for RA, and whether it is seen only with the mycobacterial homologue of this particular hsp gene family. We therefore screened antibody levels to the mycobacterial and Escherichia coli hsp 65, and the mycobacterial, E. coli, and human hsp70, in sera from RA, systemic lupus erythematosus (SLE), tuberculosis (TB), ankylosing spondylitis (AS), Crohn's disease, and control donors. RA sera show the greatest increase in IgA binding to the mycobacterial hsp65, but no increase in IgA binding to the E. coli homologue. Similarly, only RA and TB sera show increased IgG binding to the mycobacterial hsp65, and we have shown previously that the titre is greater in RA. In contrast, the use of mycobacterial and E. coli hsp70 preparations as control bacterial hsp gene products has shown that RA patients do not differ from TB or SLE patients in their antibody binding to these proteins. Moreover, neither IgA nor IgG antibody to the human hsp70 in RA sera were higher than in TB, and the IgA binding was not higher than in SLE. These findings suggest that elevated IgG antibody levels to the mycobacterial hsp65 shows some disease specificity, and further studies with the human homologue and at the T-cell level are required. | |
| 2919941 | Toxicity of methotrexate compared with azathioprine in the treatment of rheumatoid arthrit | 1989 Mar | One hundred thirty-one patients with rheumatoid arthritis treated with either azathioprine sodium (n = 37, 102.7 +/- 32.9 mg/d) or methotrexate sodium (n = 94, 8.4 +/- 3.0 mg/wk) were followed up for 38 +/- 23.3 months to determine the nature, frequency, and potential predictors of "major" toxic reactions. Thirty-one methotrexate-treated patients (33%) and 11 patients (30%) receiving azathioprine experienced a major toxic reaction during the study period. With the case-control method, no predictors of major toxic reactions secondary to azathioprine therapy were found. Sex, drug dosage, response to prior slow-acting antirheumatic drug therapy, concurrent use of salicylates, and age did not predict major toxic reactions secondary to methotrexate treatment, but the methotrexate-treated patients who experienced a major toxic reaction had a significantly greater mean level of blood urea nitrogen at the time of their reaction compared with the control group. Life-table analysis suggested toxic reactions posed a greater risk of treatment termination in methotrexate-treated patients compared with the lack or loss of efficacy. This trend was not apparent in the azathioprine group. The majority of patients in each treatment group (79 for methotrexate and 29 for azathioprine) experienced one or more "minor" toxic reactions during the follow-up period. | |
| 3121499 | In vitro effects of thymopentin on the gamma-interferon production by peripheral blood mon | 1987 Aug | The in vitro production of gamma-interferon (gamma-IFN) by peripheral blood mononuclear cells (MNC) was measured using a specific radioimmunoassay in 16 patients presenting with active rheumatoid arthritis (RA), in 14 patients with inactive disease, and in 36 control subjects (CS). Unstimulated cultures produced undetectable levels of gamma-IFN and did not incorporate tritiated thymidine. In response to phytohemagglutinin (PHA) 0.2 microgram/ml, MNC from active RA produced 9 times less, and under PHA 2.5 micrograms/ml, 4 times less gamma-IFN than did MNC from inactive RA or from CS. The uptake of tritiated thymidine was, however, similar in the 3 groups. In unstimulated cultures of the 3 groups, thymopentin (TP-5), at all concentrations tested, did not influence either the levels of gamma-IFN or the uptake of tritiated thymidine. In the presence of PHA 0.2 microgram/ml and TP-5, lambda-IFN levels were increased in CS, unchanged in inactive RA and reduced in active RA, whereas no changes were observed in the uptake of tritiated thymidine. Our results show that under our experimental conditions, TP-5 was able to increase the levels of gamma-IFN produced by normal MNC in vitro, but could not reverse the profound defect observed in active RA. | |
| 2816817 | Bone marrow findings in connective tissue disease. | 1989 Nov | The authors studied 35 marrow biopsies from 32 patients with rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disease, polymyositis, and psoriatic arthritis. Reasons for biopsy included cytopenia, fever of unknown origin, and malignancy. Cellularity was abnormal in 71%. Plasma cells were increased in 60% and associated with lymphoid aggregates. Immunoperoxidase stains showed polyclonal perivascular plasma cells and increased T-cells forming lymphoid aggregates. Two patients had granulomas without documented infection. Anemic patients had findings consistent with anemia of chronic disease, erythroid aplasia, hemolysis, and iron deficiency. Iron stores were variable. Platelet and granulocyte precursors were variably altered and did not predictably correlate with the presence, absence, or cause of thrombocytopenia and neutropenia. Myelodysplastic syndromes were present in two patients with rheumatoid arthritis. Osteomalacia and osteoporosis were seen, resulting from renal failure and steroids. Marrow findings are unpredictable and reflect the diverse causes of cytopenias in patients with connective tissue disorders. | |
| 2785013 | Lymphocyte subsets of the peripheral blood in Sjögren's syndrome and rheumatoid arthritis | 1989 Jan | Lymphocyte subsets were determined in the peripheral blood from twenty-three patients with primary Sjögren's syndrome (SS) and sixteen patients with clinically active rheumatoid arthritis (RA) by two-color flowcytometry using various monoclonal antibodies. In both diseases, T-cells (CD3+), suppressor/cytotoxic cells (CD8+) and their cytotoxic subset (CD8+CD11-) were decreased, as compared with thirty-one healthy controls. B-cells (CD 21+ and CD 3-DR+) and activated T-cells (CD 3+DR+) were increased in SS patients. Helper T-cells (CD 4+Leu8-), suppressor-inducer T-cells (CD4+Leu8+), suppressor T-cells (CD8+Leu 15+) and three natural killer (NK) cell subsets determined by both CD16 and Leu7 antibodies did not differ between controls and SS or RA, although Leu7+NK cells were significantly increased in SS patients. In addition, we found that the treatment with low-dose prednisolone decreased B-cells and suppressor-inducer T cells, and increased suppressor T-cells, cytotoxic T-cells and Leu7+NK cells. The results indicate similar changes in the proportion of lymphocyte subsets and suggest immunologically activated and deficient conditions in both diseases. Immunomodulating effects of the treatment with low-dose prednisolone on some of the lymphocyte subsets in patients with these diseases were also supported by the study. | |
| 3207388 | Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis trea | 1988 Dec | Two hundred and two patients with rheumatoid arthritis (RA) starting treatment with large doses of azathioprine (median 300 mg/day) between 1964 and 1974 were followed up until March 1984. All but one patient (99.5%) were traced from either hospital or general practice records; and death certificates, where relevant, were obtained. A comparison group of 202 patients with RA not treated with azathioprine was selected from the diagnostic index of another rheumatology unit and followed up in 1985 to assess their status retrospectively at March 1984. Each patient treated with azathioprine was matched for year of birth, year of diagnosis, sex, and serostatus with a control patient from the latter group. Four lymphoproliferative cancers occurred in the azathioprine treated group compared with two in the control group. Further analysis of these findings suggested an increased risk of lymphoma of one case per 1000 patient years of azathioprine treatment. The lymphoma rates were then compared with those expected based on the incidence in the general population. This comparison suggested a fivefold increase in the RA control group and a 10-fold increase in the azathioprine treated group. There was also an excess of patients with non-lymphoproliferative cancers, including one with myeloma in the azathioprine group (29 v 19), the excess being greater in the group with the longest duration of treatment. This significantly increased risk did not, however, persist on matched analysis, was not related to maximum daily dose, and was not site specific. These results from a possibly unique series of patients treated with high dose azathioprine give some reassurance about the magnitude of the previously postulated carcinogenic risk of such treatment in RA. | |
| 3262939 | Integrated plasma and synovial fluid pharmacokinetics of tenoxicam in patients with rheuma | 1988 | Single oral doses of 40 mg of the nonsteroidal antiinflammatory drug, tenoxicam, were given to four patients (three with rheumatoid arthritis, one with osteoarthritis). The concentrations of the drug in synovial fluid and plasma were measured by a specific high-performance liquid chromatography method. The unbound fractions of the drug in both fluids were determined at pH 7.4 and 37 degrees C by equilibrium dialysis. The possible influence of the pH on the protein binding was also assessed. The total concentration time curves in plasma and synovial fluid were fitted to linear oral 1 and 2 compartment body models with an additional synovial fluid compartment connected to the central compartment. The unbound fractions of drug in synovial fluid and plasma were on average 0.015 and 0.011, respectively: not significantly different from each other. The protein binding of tenoxicam was pH dependent with increased free fractions at pH values less than 7.4. The average peak concentrations of tenoxicam in plasma and synovial fluid were 4.3 and 1.4 micrograms/ml, respectively. The mean ratio of the areas under the total concentration time curves in synovial fluid and plasma was 0.42, which corresponded to the steady state of equilibrium ratio of the total drug concentrations in the two body fluids. Two hypotheses were tested: hypothesis I assuming that equilibration across the synovial tissue takes place between the unbound, unionized tenoxicam molecules; hypothesis II assuming that equilibration across the synovial tissue is established between the unbound (unionized + ionized) tenoxicam molecules. Based on the available evidence hypothesis II was rejected. | |
| 2060231 | Ankle arthrodesis. A comparison of internal and external fixation. | 1991 Jul | The authors reviewed the results of ankle arthrodesis in 68 ankles in 66 patients. The average follow-up period of the patients was five years (range, two to ten years). There were 40 ankles in which internal fixation was used and 28 ankles in which external fixation was used. The two groups were compared to determine the effect of mode of stabilization on outcome. Outcome was measured by time to union, development of complications, and clinical follow-up result. The groups were similar in regards to gender, age, and preoperative diagnosis. The external fixation group had a significantly higher prevalence of complications, including non-union, delayed union, and infection, than the internal fixation group. It was concluded that ankle arthrodesis with internal fixation is better tolerated and has fewer complications than techniques that use external fixation. | |
| 1990149 | Lactoferrin in rheumatoid arthritis and systemic lupus erythematous. | 1991 Jan | Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are prototypes of autoimmune diseases. In order to assess the inflammatory status in these conditions, lactoferrin, stored in specific granules of neutrophils, was measured in serum samples of patients with SLE and RA. In RA, the mean serum lactoferrin level (1221.397 +/- 289.476 ng/ml) was significantly higher than that in normal individuals (753.364 +/- 124.063 ng/ml). Surprisingly, there were no significant differences between active SLE (672.682 +/- 356.154 mg/ml) and inactive SLE (642.267 +/- 270.456 ng/ml). Still, no differences were found between normal volunteers, active SLE and inactive SLE. Serum lactoferrin in SLE correlated significantly with CRP (Rs = 0.4089, p less than 0.01), but not with complement level and ANA titers. Thus in RA serum lactoferrin was highly elevated and this indicated that PMN in systemic circulation was activated. In SLE the correlation of CRP with lactoferrin reflected the role of later protein in inflammation. |