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

PMID	Title	PublicationDate	abstract
2059229	Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthr	1991 Jul	Increased serum levels of hyaluronate (HA) have been found in patients with rheumatoid arthritis (RA). This probably reflects increased leakage of HA from the inflamed joints into the circulation. In a prospective study of 40 patients with early RA, we evaluated the relationship of serum HA to clinical, laboratory, and radiologic parameters of disease activity. The patients were followed for 12 months; all had active disease at study entry. We confirmed the previous finding of higher serum HA concentrations in RA patients compared with healthy controls. At study entry, the patients' serum HA levels correlated positively with clinical and laboratory parameters of acute inflammation. Despite marked clinical improvement during therapy with second-line drugs, the serum HA levels increased during the followup period. At the end of 1 year, these levels correlated with the radiologic progression of joint lesions, whereas they showed a less pronounced correlation with clinical or laboratory parameters of inflammation. We conclude that, in early RA, serum HA levels may reflect ongoing joint destruction and may even predict subsequent joint damage.
2833238	Immunological detection of myeloperoxidase in synovial fluid from patients with rheumatoid	1988 Feb 15	We have used rocket immunoelectrophoresis and immunoblotting to detect myeloperoxidase in synovial fluid from patients with rheumatoid arthritis. This protein was enzymatically inactive but its identity as myeloperoxidase was confirmed by comparing its subunit structure with that of the purified enzyme. When neutrophils were stimulated to secrete myeloperoxidase in vitro, a polypeptide with an apparent molecular mass of 62 kDa was detected extracellularly by immunoblotting. Neutrophils isolated from synovial fluid showed a reduced level of this 62 kDa polypeptide but it was detected extracellularly in synovial fluid by immunoblotting. Thus, we conclude that neutrophils in synovial fluid from patients with rheumatoid arthritis have been activated in vivo to secrete myeloperoxidase and propose that the products of this enzyme system can contribute to the tissue damage associated with this disease.
2360425	Humeral cup fixation in rheumatoid shoulders. Roentgen stereophotogrammetry of 12 cases.	1990 Apr	Twelve shoulders in 10 patients with rheumatoid arthritis were treated with cemented cup hemiarthroplasty and examined by roentgen stereo photogrammetry during the first year after surgery. One cup migrated 0.5 mm while 11 remained well fixed. Our findings suggest that long-term prosthetic fixation may be achieved.
3355249	Serum amino terminal type III procollagen peptide and serum hyaluronan in rheumatoid arthr	1988 Feb	Increased serum levels of the amino terminal type III procollagen peptide and serum hyaluronan were demonstrated in patients with rheumatoid arthritis. In patients with active disease a significant correlation was shown between serum levels of the propeptide and hyaluronan and the clinical signs of synovitis reflecting the extent of synovial inflammation. During recovery the serum propeptide and serum hyaluronan showed a delayed decline as compared with the clinical signs of synovitis and the acute phase protein response. This probably reflects the presence of persistent subclinical chronic inflammation. Normal serum propeptide levels in rheumatoid arthritis were associated with a good prognosis without progression of erosive joint lesions. Azathioprine reduced the number of patients with progression of erosive joint lesions and caused a more marked suppression of the serum propeptide than levamisole and penicillamine.
3075073	The T cell system in rheumatoid arthritis: activated or defective?	1988	Rheumatoid Arthritis (RA) is characterised by the presence of activated lymphocytes in the synovial compartment, which are classically considered to be of particular importance to the pathogenesis of the disease. We have shown that activated lymphocytes are also found in the rheumatoid lymph nodes and peripheral blood, and that their proportions are increased in early or active disease. Double-labelling experiments showed that T cell subsets within the activated circulating lymphocytes resemble closely those found in the synovium, and suggested an important role for circulating activated lymphoid populations in the pathogenesis of RA. In vitro studies indicate that although rheumatoid lymphocytes express activation markers, they are functionally deficient. This is well established in the case of synovial lymphocytes. We have demonstrated that functional defects are also present in circulating rheumatoid lymphocytes, which show a decreased autologous mixed leucocyte response (AMLR), corrected partially by the addition of exogenous IL-2. They also proliferate poorly in response to PHA and produce significantly less IL-2 than normal controls. This is more marked in patients with active or complicated RA. These defects cannot be explained by a lack of CD4+2H4+ cells which we have shown to be the major IL-2-producing circulating lymphocyte subpopulation. These findings suggest an intrinsic-functional rather than a numerical deficiency of the IL-2 producing T cells in RA. In recent experiments we have shown that non-lymphoid populations, such as activated phagocytic cells, are also involved in the deficient rheumatoid T cell function, partly via the production of prostaglandins and reactive oxygen intermediates. We and others have demonstrated that the latter may significantly and selectively affect lymphocyte viability and function. These findings may explain the differences in the functional capacity of lymphocytes frequently observed between cells derived from different sites or at different stages of the disease. We suggest that it is not lymphocyte activation as such, but its defective nature, that is of pathogenetical importance in RA. Furthermore, the T cell system should not be viewed and studied in isolation in this disease, but its interactions with inflammatory cells should be taken into account.
2068577	Long-term methotrexate therapy for rheumatoid arthritis.	1991 Apr	A retrospective review of methotrexate (MTX) treatment assessed the clinical course in 124 rheumatoid arthritis (RA) patients. After 5 years, 39 (31%) patients continued MTX with clinical benefit. Although patients continuing MTX after 5 years were younger (45 +/- 13 v 54 +/- 12 yrs, P less than .001) and had a shorter disease duration of RA (9.3 +/- 8.1 v 14 +/- 11 yrs, P less than .05) than patients who discontinue the drug, these differences were not considered clinically significant. MTX was discontinued in 20 patients for a lack of clinical benefit, in 21 patients for non-drug-related reasons, and in 44 patients for suspected adverse drug reactions. The adverse drug reactions requiring permanent discontinuation of MTX were nausea, stomatitis, hair loss, rash, pulmonary reactions, elevated liver enzymes, hematologic abnormalities, and hepatic fibrosis. At least one adverse drug reaction was reported by 115 (93%) patients receiving MTX, but the majority did not require permanent drug discontinuation. Although the prevalence of adverse reactions increased with longer duration of therapy, no differences existed in the type of reactions reported over 5 years of treatment. There were no risk factors identified that were clearly associated with the development of toxicity. Long-term therapy was primarily limited by adverse reactions rather than loss of efficacy.
2246196	Changes in bronchoalveolar lavage and lung function in rheumatoid arthritis. A controlled	1990 Aug	A comparative study of bronchoalveolar lavage was done in 30 patients with chronic rheumatoid arthritis and 30 age matched controls. Twelve patients had clinical lung disease (group I), 11 had lavage changes (group II) and 7 showed no abnormalities (group III). In group I, there was lower lung functions, tendency to older age and slightly longer history. There were no differences between the three groups (63% positive) in RA factor positivity. In the controls, lavage showed 67.3% return, 154.5 cells/cmm, 92.8% macrophages, 5.2% lymphocytes, 1.9% polymorphs and 0.2% eosinophils. In contrast, group I patients showed more polymorphs (10.3 +/- 8.3%) and group II more lymphocytes (14.5 +/- 18.7%; P less than 0.05). Thus, in chronic rheumatoid arthritic patients, bronchoalveolar lavage abnormalities may occur alone or in association with radiographic and functional abnormalities.
1887414	[Blood serum and synovial fluid proteins in Reiter's syndrome].	1991	Individual proteins (transferrin, ceruloplasmin, alpha 2-macroglobulin, IgG, IgA and IgM) were examined in blood and synovial fluid of 11 patients with Reiter's syndrome. ARA-1981 was used as a diagnostic criteria. The control group included 40 patients with rheumatoid arthritis and 31 with osteoarthrosis of the knee joint. Statistically significant differences between the concentrations of individual proteins in patients with Reiter's syndrome, rheumatoid arthritis and osteoarthritis were only established in synovial fluid for IgM and for IgM index Csf/CS.
2038870	[HLA-antigens in patients with rheumatoid arthritis].	1991 Jan	109 patients with rheumatoid arthritis (RA) from the north of the GDR were HLA typed and the antigen frequencies compared with those of a control group. Even in our patients the HLA-DR4 association was demonstrable. But in all studies DR4 association is not strong enough for taking HLA typing as a diagnostic test for RA. There was an immunogenetic heterogeneity in correlation to side effects of therapy with sodium aurothiomalate or D-penicillamine. HLA-DR5 was significantly increased in patients with side effects in comparison to patients without side effects in therapy. Before recommending HLA-DR typing for selection of high risk patients in D-penicillamine therapy these results should be proven in a large patient group or in a second study.
3262910	Activated T lymphocytes, rheumatoid factor and erythrocyte sedimentation rate assays in rh	1988	Activated T lymphocytes (Ia+ T-cells) in peripheral blood are associated with immune stimulation. We found the percentages of these cells significantly increased in 95% of rheumatoid arthritis (RA) patients. Our studies showed no relation between the percentages of these cells in peripheral blood and concurrent erythrocyte sedimentation rates or rheumatoid factor titers. Circulating immune complex titers determined in a small number of patients conjectured an association with Ia+ T-cell levels.
1905130	T lymphocyte-synovial fibroblast interactions induced by mycobacterial proteins in rheumat	1991 Jun	An in vitro system was established in which single-cell suspensions of lymphocytes and synovial cells from the joints of patients with rheumatoid arthritis were cultured and produced an outgrowth of an organized inflammatory tissue with an extracellular matrix and capsule. The tissue outgrowth, which had histologic features of pannus, required the addition of mycobacterial antigen and interleukin-2 to the tissue culture medium and was dependent upon the presence of T lymphocytes and their interaction with synovial fibroblasts.
1906935	A double blind randomized parallel trial of intramuscular methotrexate and gold sodium thi	1991 Mar	In a double blind study 57 patients with active erosive rheumatoid arthritis without malalignment or deformities (median disease duration 13 months) were randomly treated with 50 mg gold sodium thiomalate (GSTM) or 15 mg methotrexate (MTX) intramuscularly for 6 months. In the GSTM group, 5/28 patients had to be withdrawn because of side effects; in 2/28 the dose was reduced. In the MTX group, 2/29 were withdrawn, one was lost to followup. The number of swollen joints improved by over 6 in 18/26 (MTX) and in 15/21 (GSTM). Five clinical variables and the sedimentation rate improved significantly in both groups without significant intergroup differences. The radiographs of hands, wrists and forefeet (32 joints evaluated according to Larsen) showed a radiological progression in 11/26 (MTX) and in 8/20 patients (GSTM); however, the deterioration of the mean Larsen index was not significant. While there was no significant difference in effectivity, tolerability was better in the MTX group.
2241261	Oral contraceptives and rheumatoid arthritis: new data from the Royal College of General P	1990 Oct	From data available at April 1987 it was found that the standardised risk ratio for rheumatoid arthritis between current users of oral contraceptives and never users was 0.82 (95% confidence interval 0.59 to 1.15); the ratio between former users and never users was 0.94 (95% confidence interval 0.72 to 1.22). Important secular trends have occurred within our study population. The incidence of rheumatoid arthritis among former and never users has declined over the past two decades. Current users have not experienced this temporal trend, and the ratio between current and never users has, therefore, approached unity. These secular changes may explain why some studies have found that oral contraceptives have a protective effect, while others have been unable to show such an effect.
2345085	Problems with the Steinbrocker staging system for radiographic assessment of the rheumatoi	1990 May	Hand and wrist radiographs of 202 patients with rheumatoid arthritis were graded with the classical Steinbrocker Staging System, and were also assigned quantitative scores for joint space narrowing, erosion, and malalignment according to a detailed scoring method. Steinbrocker Stage scores were correlated significantly with total detailed scores (r = 0.60 to 0.66, P less than 0.001). However, the ranges of detailed total and subtotal scores among the various Steinbrocker Stage scores were broad, with considerable overlap. Practical problems in applying the Steinbrocker staging method were identified in 26.5% of the hands graded with the Steinbrocker method. Additionally, analysis of scoring data showed discrepancies between the scoring methods in 25.2% of the hands examined; one-half of these discrepancies were felt to result from the global or overall approach of the Steinbrocker method in contrast to individual joint analysis. Asymmetry in assigned stages between right and left hands was found in 15.8% of patients. The detailed scoring method, although more time-consuming, appears superior to the Steinbrocker Stage for quantitative assessment of patient radiographic status in rheumatoid arthritis.
2949993	[Pathological study of Streptococcus faecalis antigen-induced arthritis in New Zealand whi	1987 Jan	The pathological examination of the rabbit knee joint with antigen-induced arthritis produced by heat-killed Streptococcus faecalis (Str. faec.) as antigen was carried out. Macroscopically, there were findings of acute inflammation about five hours after the injection. Histopathologically, very remarkable acute exudative inflammation was seen 48 hours later. This supported the picture of Arthus reaction. The Arthus reaction disappeared with time, and this supported the view of delayed-type hypersensitivity three weeks later. After that, an obvious chronic inflammation was admitted in 10 weeks. This resembled the histopathological feature of rheumatoid arthritis (RA) when these findings are summarized. It was suggested that arthritis produced by Str. faec. progresses from an acute condition to a one with time. As mentioned above, it thought that Arthus reaction of both immediate hypersensitivity and delayed-type hypersensitivity are necessary in the occurrence of this arthritis.
3763217	[Planning surgical treatment].	1986 Aug	The following should be regarded as prerequisites for successful surgical treatment: careful assessment of the local problem and of the patient as a complete individual; a thorough understanding of the biomechanical implications of the disease and of the operations used in its management; a clear definition of the goals of surgery in both the patient's and the surgeon's minds; and very careful planning with regard to the timing and sequence of operations. Other factors of major importance, especially in multijoint reconstructive programmes, are careful patient selection, the early establishment of good doctor/patient rapport, the support of a highly skilled multidisciplinary team of health professionals, and impeccable supervision of the convalescence, especially at the particularly difficult period for the patient following discharge from hospital. Finally, the hospital team must be prepared to offer a permanent service as a readily available advice bureau for family doctors, patients, and their relatives.
3723494	Measures of immunologic and inflammatory responses in vitro in rheumatoid patients treated	1986 Apr	We examined the effects of low dose parenteral methotrexate (MTX) on immunologic and inflammatory responses of potential importance in the pathogenesis of rheumatoid arthritis. Only 2 significant changes were noted: the number of esterase positive cells in the peripheral blood decreased, and the uptake of tritiated thymidine by incubated peripheral blood mononuclear cells fell markedly. These changes were present 48 h after an injection of MTX, before decreased disease activity became clinically apparent. We therefore conclude that they were direct effects of the drug itself.
1681103	Study of a restriction fragment length polymorphism for serum amyloid P gene in rheumatoid	1991 Jul	Amyloidosis is a severe complication of rheumatoid arthritis (RA). A restriction fragment length polymorphism (RFLP) using MspI for the serum amyloid P gene was recently found to be associated with amyloidosis in juvenile arthritis. The aim of our study was to determine whether this RFLP could serve as a genetic marker for the development of secondary amyloidosis in RA. The prevalence of this marker was determined in 4 groups of patients: patients with amyloidosis secondary to RA; with amyloidosis secondary to various diseases excluding RA; with RA but without amyloidosis; adult controls without any known disease related to reactive amyloidosis. No significant differences were seen between these 4 groups with relation to this polymorphism, so that it cannot serve as a genetic marker for amyloidosis complicating RA in our population.
3947405	Assessment of radiologic progression in rheumatoid arthritis. A randomized, controlled tri	1986 Jan	Radiologic assessment of progressive joint destruction in rheumatoid arthritis is generally considered to be the ultimate standard for evaluation of treatment. We compared alternative radiologic techniques by performing a randomized, controlled trial in which hand films of rheumatoid arthritis patients were read by several skilled observes. The number of joints evaluated (34 versus 18) was found to make relatively little difference, but the number of readers and their experience level was critical. Films should be read in pairs. Joint space narrowing and erosion scores were shown to contribute independent information. Use of recommended techniques can reduce the number of patients required and, thus, can reduce the cost of a clinical trial by more than half and can substantially increase the sensitivity and efficiency of a trial. Therefore, critical selection of the method of assessing study endpoint is of great importance.
2442919	The use of the AIMS questionnaire in the evaluation of sulphasalazine treatment in rheumat	1987 May	For evaluation of a one-year open clinical trial with sulphasalazine, apart from monitoring clinical and laboratory parameters, the self-administered questionnaire AIMS (Arthritis Impact Measurement Scales) was used. This method makes it possible to obtain information on functional and psychosocial aspects of a patient's health status. The trial started with 30 patients with active rheumatoid arthritis. During the trial, ten patients were withdrawn (eight for adverse reactions, two for inefficacy). In patients who completed the study, the results proved that over the course of 12 months' therapy with sulphasalazine, most of the scores obtained from AIMS gradually improved. Statistical correlation of standard clinical and laboratory parameters with health status measures was evident for most of these variables. These preliminary results suggest that a questionnaire of the AIMS type may be a useful means of outcome assessment of rheumatoid arthritis in clinical trials.