Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7612412 | Inherited and noninherited risk factors in rheumatoid arthritis. | 1995 May | Rheumatoid arthritis (RA) is likely the result of a concerted action of several inherited and noninherited factors. Although there is a high suspicion that environmental factors are important, proof is missing. Most information has been collected on genetic risk factors. The inheritance pattern for RA is complex, and there is good evidence that HLA as well as non-HLA genes are involved. Almost all racial-ethnic groups share the association of RA with the HLA-DRB1-encoded sequence motif QKRAA or QRRAA. However, the completeness of the association varies significantly in different ethnic cohorts, as can be expected in a multigene model. The sequence motif translates into a pocket in the antigen-binding site of the HLA-DR molecule. The "rheumatoid pocket" accommodates peptide side chains and has distinct binding characteristics. Epidemiologic evidence points toward a role for non-HLA genes. Candidate genes, such as transporter in antigen processing (TAP) genes are currently explored. Major advances in defining and understanding the contribution of inherited and noninherited factors in RA may come from abandoning the concept of RA as a single entity and accepting a heterogeneity model for RA. Distributions of HLA-DR genes indicate that several subsets of RA patients exist. Seronegative (prognostically good) and seropositive (prognostically worse) patients can be distinguished by the arginine versus lysine substitution at position 71 of the HLA-DRB1 gene. A different dimension of disease, rheumatoid organ disease, appears to be reached in patients with two HLA-DRB1*0401 alleles. Identification of distinct RA subsets may allow us to stratify patients into categories that differ with respect to etiology, disease course, clinical pattern, and treatment response. | |
| 7851956 | Associations of IgA and IgA-rheumatoid factor with disease features in patients with rheum | 1994 Nov | In previous studies we have shown that levels of IgM-rheumatoid factor (RF) in plasma and peripheral blood mononuclear cell supernatants are correlated with disease activity and response to second-line therapy in patients with rheumatoid arthritis (RA). The present studies were designed to examine whether IgA-RF levels are also correlated with clinical features of this disease. Two groups of RA patients were studied. Group I consisted of 87 patients in whom extensive clinical data had been collected. Group II included nine patients beginning treatment with gold or methotrexate who were studied during the first year of therapy. Measurement of IgM, IgA, IgM-RF and IgA-RF in culture supernatants and plasma was done by an ELISA method. These data were examined for correlations with clinical and laboratory features. Levels of IgA-RF in supernatants and plasma were found not to be correlated with disease features in the cross-sectional analysis of Group I patients, while IgM-RF and total IgA levels did show significant clinical correlation. Treatment of Group II patients with gold or methotrexate was associated with significant decreases in plasma levels of total IgA and IgM-RF as well as a small but statistically significant decrease in plasma IgA-RF. Plasma levels of total IgM were not altered during therapy. These findings suggest that production of IgA but not IgA-RF is correlated with disease status in patients with RA. | |
| 8588126 | D-penicillamine and gold salt treatments were complicated by myasthenia and pemphigus, res | 1995 | A 53-year-old woman with rheumatoid arthritis developed myasthenia gravis after 6 months of therapy with D-penicillamine. Nineteen months after D-penicillamine was discontinued and 12 months after the beginning of gold therapy, she developed pemphigus vulgaris. This is the first reported case of gold-induced pemphigus in rheumatoid arthritis. This study further underlines the complex interactions between the effects of treatment with sulfhydryl-disulfide exchange drugs and the altered immunological system of patients affected by rheumatoid arthritis. | |
| 7686831 | Differential patterns of response in patients with rheumatoid arthritis following administ | 1993 Mar | As part of the clinical investigation of a new biologic agent in the treatment of rheumatoid arthritis (RA) various outcome measures were utilized to evaluate clinical activity in two multicenter open label protocols. These measures included the single criteria of joint tenderness and swelling counts and scores and composite criteria based on the Paulus analysis of four placebo-controlled CSSRD studies of second line agents in RA. Findings suggest a difference in the pattern of response between early and long-standing RA. Changes in both the swollen and tender joint counts should be utilized, especially in a population with sustained disease. | |
| 1737237 | A generic health status instrument in the assessment of rheumatoid arthritis. | 1992 Feb | Seventy-three patients with RA were assessed by means of the Nottingham Health Profile (NHP), the Arthritis Impact Measurement Scales (AIMS) and a number of clinical measures. Patients with RA scored higher than controls on the NHP scales for energy, pain, mobility and sleep. Energy, pain, mobility and emotions scales of the NHP correlate significantly with other measures such as clinical assessments, matching scales of the AIMS and the Beck Depression Inventory, indicating satisfactory validity for the instrument with RA. Five of the six scales of the NHP are stable on retesting. The social scale of the NHP on the other hand does not correlate with the matching instrument of the AIMS and is relatively unstable over time. Measurement properties of generic health status instruments such as the NHP will require serious attention as they are increasingly used in evaluation studies. | |
| 9102073 | [Active forms of oxygen and pathogenesis of rheumatoid arthritis and systemic lupus erythe | 1996 | In this paper the authors underline the significance of studies into the body's free radical oxidation, analyze the involvement of free radical reactions in the maintenance of homeostasis. They indicate that free radical metabolic changes leading to oxidative stress play a role in the pathogenesis of many human diseases. Particular emphasis is laid on the contribution of active forms of oxygen (AFO) in the development of autoimmune diseases, including rheumatic diseases. The history of this problem is outlined. There are examples that confirm the enhancement of free radical processes and the inhibition of the antioxidative system in rheumatic arthritis (RA) and some other rheumatic diseases. The essential drugs used in the treatment of RA patients are demonstrated to also act due to the inhibited "respiratory outbreak" of phagocytes. The key point of the paper is the role of free radical reactions in the pathogenesis of systemic lupus erythematosus (SLE). There is evidence suggesting that there is a reduction in antioxidative defense and a rise in neutrophilic production of AFO in SLE patients. Consideration is also given to the possible participation of AFO in the formation of DNA antibodies, the effects of AFO on the immune system, atherogenesis in SLE. Taking into account a possible contribution of AFO in the pathogenesis of SLE, it is expedient to include antiradical agents into the multimodality therapy for this disease and promising to continue investigations in this field. | |
| 8957109 | What is the mechanism of action of anti-tumour necrosis factor-alpha antibody in rheumatoi | 1996 Dec | The rationale for anti-tumour necrosis factor-alpha (anti-TNFalpha) therapy in rheumatoid arthritis (RA) is based on experiments on cultures of human rheumatoidjoint tissue, supported by experiments in animal models, all of which demonstrated that anti-TNFalpha antibody had profound effects on the disease activity. Clinical trials have substantiated this concept, and we have used the serum samples from the clinical trials, as well as biopsies to study the changes occurring during anti-TNFalpha therapy as clues to the pathogenesis of RA. The major effects of anti-TNFalpha therapy are in downregulating cytokine activity, and in reducing leucocyte trafficking to the joints. | |
| 8876582 | Results of total elbow arthroplasty after excision of the radial head and synovectomy in p | 1996 Oct | We compared the results of twenty-three consecutive capitellocondylar total elbow arthroplasties in twenty-three patients in whom an excision of the radial head and synovectomy for rheumatoid arthritis had failed with those of twenty-three non-consecutive primary capitellocondylar total elbow arthroplasties in twenty-three patients who had rheumatoid arthritis. The two groups were matched for age, gender, duration of follow-up, side of the operation, type of prosthesis, and operative approach. The average duration of follow-up was four years (range, two to fourteen years). At the most recent follow-up examination, use of a 100-point rating system demonstrated an improvement from an average preoperative score of 21 points (range, 12 to 42 points) to an average postoperative score of 87 points (range, 17 to 97 points) for the group in whom an excision of the radial head and synovectomy had failed. The group that had primary arthroplasty demonstrated an improvement from an average preoperative score of 22 points (range, 7 to 42 points) to an average postoperative score of 94 points (range, 85 to 100 points). The group that had primary arthroplasty had a significantly greater improvement in terms of relief of pain (p < 0.05), functional status (p < 0.01), and the elbow-rating score (p < 0.03) than the other group. Four patients who had had failure of an excision of the radial head and synovectomy and none of those who had primary arthroplasty needed an additional operative procedure. Six of the patients who had had a failed excision and synovectomy and none of the patients who had primary arthroplasty had instability of the elbow components. We concluded that, although excision of the radial head and synovectomy is a conservative and effective method of treating a painful rheumatoid elbow, conversion to a capitellocondylar total elbow arthroplasty is more difficult after such an operation and the results at a minimum of two years are inferior to those for primary capitellocondylar total elbow arthroplasty. | |
| 7602306 | Medical treatment of rheumatoid arthritis. | 1995 May | The outcome of rheumatoid arthritis in a single patient is frustratingly variable and unpredictable, but the illness leads to progressive disability in the majority of sufferers. Careful and continuous follow-up, aggressive medical treatment, an individualized exercise and dietary program, constant education and training, and psychological support are all important to enable the patient to maintain independence in daily living and in sustaining a home life and career. Multiple new medical therapies and strategies are being developed. At present, combination therapy with currently available drugs seems to be the most pragmatic tactic to control the patient with otherwise refractory disease. | |
| 1556688 | Pregnancy outcome in women with rheumatoid arthritis before disease onset. | 1992 Jan | Pregnancy outcome before disease onset was evaluated for women with rheumatoid arthritis (RA) and control women as part of a prospective case-control study of newly diagnosed RA. An analysis of women who were ever gravid revealed no statistically significant difference in any adverse pregnancy outcome between RA cases (n = 144) and controls (n = 605) including spontaneous abortions and stillbirths. Thus, in contrast to reports both of an increase of adverse pregnancy outcomes and a decrease in women who subsequently develop RA, we found no evidence for any difference in pregnancy outcome in the RA group. | |
| 1575574 | Increased prevalence of poor sulphoxidation in patients with rheumatoid arthritis: effect | 1992 Mar | A minority of normal subjects have an impaired ability to oxidise sulphur, which is associated with an increased risk of side effects when they receive sulphur containing drugs. In 114 patients with rheumatoid arthritis a greatly increased prevalence of poor sulphoxidation was found in 82 (72%) patients compared with 70/200 (35%) healthy controls, 45/121 (37%) controls matched for age, and 4/35 (11%) of the normal aged general population. In a longitudinal study of 37 patients there was no significant alteration in sulphoxidation status after the introduction of a second line drug or with marked changes in the acute phase response. It seems, therefore, that the poor sulphoxidation status in patients with RA is not an epiphenomenon and may be an important factor in determining the clinical features of rheumatoid disease. | |
| 8493583 | [Study of synovial lesions by MRI using gadolinium-DTPA (Gd-DTPA) in patient with early ph | 1993 Feb | To evaluate the usefulness of magnetic resonance imaging (MRI) enhanced with gadolinium-DTPA (Gd-DTPA) for the detection of the inflamed synovium and for the evaluation of the response to therapy in rheumatoid arthritis, we studied 49 patients with rheumatoid arthritis (RA) according to the 1987 revised criteria of American Rheumatism Association (ARA), 6 patients of systemic lupus erythematosus (SLE) complicated by arthritis, 3 patients of osteoarthritis (OA), 2 patients of Sjögren syndrome, 2 patients of progressive systemic sclerosis and 10 healthy volunteers as an age matched control. The 49 patients with RA were divided into three groups: (1) early phase of RA, (2) non progressing RA and (3) slowly progressing RA, and the stage classification of plain X-ray film and enhancement pattern of MR images were classified into three groups. Synovial enhancement showed a linear, band-like or diffuse pattern. Almost all cases in early phase of RA group and non progressing RA group showed a linear pattern, a band-like pattern or even no enhancement, while slowly progressing group of stage II or higher showed the diffuse pattern of enhancement in all except 2 cases. Moreover, the linear pattern, the band-like pattern or even no contrast enhancement were seen in all except 1 stage I patient, whereas 26 out of 29 patients with stage II or higher change showed diffuse contrast enhancement. Furthermore, a comparison of MR images before and after administration of DMARDs in 10 patients showed that the improvement of clinical symptoms correlated fairly well with reduction of contrast enhancement.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 8299255 | Distal metacarpal bone mineral density by dual energy X-ray absorptiometry (DEXA) scan. Me | 1993 Nov | Dual energy X-ray absorptiometry scanning was performed along the axis of the third metacarpal bone of the non-dominant hand and including metacarpal bones 2, 3, 4 and 5. The Bone Mineral Density (BMD) was calculated for the distal 1/4 of each metacarpal bone. Ten patients with seropositive, erosive rheumatoid arthritis (RA) and 10 healthy, sex- and age-matched persons were investigated twice. The average BMD in RA patients was 73.6% of the value found in normals. The coefficient of variation on double determinations (in patients and controls) was 0.9-3.0%. We suggest that dual energy X-ray absorptiometry scanning with the scanning procedure proposed here may be an important instrument for the quantification of disease progression. | |
| 1537161 | The anterior cruciate ligament in knee arthroplasty. A risk-factor with unconstrained meni | 1992 Mar | Three hundred one unconstrained meniscal arthroplasties were observed for as long as nine years, during which time 25 (8.3%) failed. Risk factors were sought by comparing the distributions of several preoperative variables in the group that failed with the group that was successful. Age, weight, the magnitude or direction of preoperative deformity, and the presence of postoperative malalignment were all without effect on the outcome of the operations. Knees with rheumatoid arthritis had a 95% survival rate at six years. Knees with osteoarthrosis had an equivalent survival rate of 83%. Knees in which the anterior cruciate ligament (ACL) was normal had a survival rate of 95% at six years; those in which the ligament was damaged or absent had an equivalent survival rate of 81%. Successful reconstruction of a knee with an unconstrained meniscal implant requires the presence and the preservation of an intact ACL. | |
| 8434242 | Characterization and functional assessment of patients subjected to occipito-cervical fusi | 1993 | 20 patients with rheumatoid arthritis and atlanto-axial dislocation subjected to occipito-cervical fusion were studied. The patients were evaluated by a rheumatologist before surgery and 6-12 months after the fusion procedure. Joint tenderness was assessed by Ritchie's Index while the functional capacity was evaluated using a health assessment questionnaire and according to the classification by Steinbrocker. Localization and character of the symptoms from the head-neck region were registered. The neck pain was measured on a visual analogue scale. Radiographs of hands and wrists were obtained before surgery and joint destruction was classified according to the Larsen Dale Index. Reduction of pain and neurological symptoms was observed in the majority. There was, however, little evidence of improved functional capacity. | |
| 8829695 | The connective tissue diseases and the overall influence of gender. | 1996 Mar | The autoimmune diseases are more common in women than men. The actual prevalence ranges from the high of 10 to 15 females for each male for systemic lupus erythematosus to four females for every male with rheumatoid arthritis. Though these diseases are found in the very young and the aged, the high prevalence is observed after puberty in most patients. These diseases vary with regard to severity, and most investigators suspect that the signs and symptoms of these diseases vary with menstrual cycle and change severity during pregnancy. The collagen diseases are devastating to the health of young women. Rheumatoid arthritis occurring at a mean age of 40 years results in debilitating erosive changes in bone with morning stiffness and eventual crippling. Systemic lupus erythematosus, Sjögren's syndrome and others, common to women of the childbearing years, act in several ways to destroy organ systems of the body. Virtually any organ system of the female anatomy can be affected by these illnesses. In the case of lupus, the disease has protean manifestations, such as procoagulation, renal destruction, skin disease, unrelenting arthropathy and arthritis, and encephalopathy (to name only a few). The underlying mechanisms are not known; however, the immune system acts to destroy tissue via immune complex deposition and through the action of cytotoxic lymphocyte activity. There is an association of both clinical signs and autoantibody subpopulations with markers of the HLA-D or MHC II locus on chromosome 6. No constitutive gene for any of the collagen vascular diseases has been identified in the human. Evidence exists to support an altered metabolism of estrogens and androgens in patients with these diseases. Recent data also indicate that increased estrogen levels might initiate autoimmune diseases in many women and men. Estrogen hydroxylation is increased in both men and women with autoimmune diseases like lupus. The mechanisms are unknown, although estrogenic metabolites have been shown to increase B cell differentiation and activate T cells. Moreover, isolated cases of hyperprolactinemia have been observed in association with these hyperestrogenic states, and treatment of hyperprolactinemia has been shown to ameliorate diseases like lupus. Androgen oxidation is also increased in patients with autoimmune disease, but this abnormality has been observed only in patients with lupus, and only women at that. The result is that women with autoimmune diseases like lupus and rheumatoid arthritis have lower plasma androgens than control cases. These data have supported the use of weak androgens, e.g., DHEA, for the treatment of lupus. | |
| 8504324 | The future of rheumatoid arthritis treatment. | 1993 Apr | Research into the molecular mechanisms of immunological diseases and the development of more specific therapies are moving ahead simultaneously at a rapid pace. This information may provide a better paradigm for understanding the pathogenesis and the prospects for interventional immunotherapy of RA. | |
| 8583865 | Noninvasive 3D MR microscopy as a tool in pharmacological research: application to a model | 1995 | Magnetic resonance microscopy (MRM) was applied to noninvasively image skeletal structures in the hindpaw of the live rat to characterize the progression of a heterologous type II collagen-induced arthritic process. Using a resonator, with optimized filling factor, three-dimensional (3D) gradient-echo images with voxel dimensions of 94 x 81 x 60 micron3 were acquired in 54.6 min. Three-dimensional MRM reduces the slice positioning problem, which is critical in longitudinal studies. Moreover, due to the much smaller slice thickness of images derived from 3D data sets, partial volume effects are less pronounced than in corresponding 2D images. Distinct pathomorphological changes associated with the collagen-induced arthritic process (e.g., increase of metatarsophalangeal joint space, and bone and cartilage erosion) could thus be analyzed under in vivo conditions. | |
| 7803916 | Renal thrombotic microangiopathy in a patient with rheumatoid arthritis and antiphospholip | 1994 Aug | A female patient with a history of migraines and chorea developed polyarthralgia at age 24 and was diagnosed with rheumatoid arthritis. In 1991 she was hospitalized because of impaired renal function and hypertension. Examination revealed thrombocytopenia and the presence of lupus anticoagulant. Antinuclear antibody was weakly positive, but anti-DNA antibody was negative, and no decrease in leukocyte count or complement level was observed. Rheumatoid arthritis with antiphospholipid syndrome was diagnosed. Renal biopsy showed renal thrombotic microangiopathy. This renal lesion was considered to be associated with antiphospholipid syndrome. Cyclophosphamide pulse therapy and anticoagulation therapy decreased proteinuria and improved renal function. | |
| 7656341 | Classification criteria for rheumatoid arthritis. | 1995 May | The development of classification schemes for RA in the last 40 years has followed the increasingly precise understanding of the nature of the clinical disease and the recognition of the different requirements of classification methods in clinic and population settings. In published studies of RA in clinic patients the most widely used criteria sets have been the 1958 ARA (ACR) criteria and its 1961 adaptation (the Rome (active) criteria). These sets classified disease as 'classical', 'definite', 'probable' and 'possible' RA based on criteria comprising clinical, serological, radiological and histological features (the latter were dropped from the Rome criteria set because of their impracticality). More recently, a new criteria set (the 1987 ARA criteria) has been developed using statistical techniques. This set was derived using RA cases and controls attending hospital clinics. It is based on the earlier criteria sets but accommodates the characteristic pattern of joint involvement in RA more precisely. The criteria recognize only the single disease category of 'rheumatoid arthritis'. In validation studies, the 1987 criteria set has been found to have enhanced specificity over earlier schemes in clinic-based studies of RA. The sensitivity may, however, be reduced, in particular in studies of early disease. The application of classification criteria for case recognition in the population and family studies of RA has proved more problematic. In these settings, there is the additional requirement to recognize individuals with remitted and inactive disease as RA cases. The 1966 New York criteria were developed for this specific purpose, however their format proved cumbersome and they have not been widely adopted. The 1987 criteria set is insufficiently sensitive to recognize inactive disease if the criteria are applied exactly as they have been defined. The sensitivity of the 1987 criteria set is, however, substantially enhanced if the criteria are adapted to incorporate features of past disease activity, for example by allowing deformity to substitute for swelling and by incorporating data on the past occurrence of rheumatoid factor and rheumatoid nodules. Developments in the immunology and genetics of RA may in the future provide more accurate tools for classification and may lead to recognition of more precise disease subsets. At present, however, the 1987 ARA criteria provide the most appropriate basis for case recognition in both clinic and population-based studies. |