Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 7763110 | High resolution computed tomography of the lung in lifelong non-smoking patients with rheu | 1995 Apr | OBJECTIVES: To define pulmonary involvement on high resolution computed tomography (HRCT) of the thorax in lifelong non-smoking rheumatoid arthritis patients and to relate the results to pulmonary function, bronchial reactivity, and a variety of clinical and serological factors. METHODS: Twenty lifelong non-smoking RA patients (mean age 59 years (range 44-72; 18 females) were studied. Detailed medical and drug histories were taken. Protease inhibitor phenotype (Pi) and HLA-DR4 status were assessed. Schirmer's tear tests were performed to detect keratoconjunctivitis sicca (KCS). Spirometry, flow volume loops, and gas transfer factor measurement were recorded. The degree of bronchial reactivity (PC20 FEV1) was measured by a methacholine inhalation test. Chest and hand radiographs and HRCT of the lung were performed in all patients. RESULTS: Thirteen patients were HLA-DR4 positive. Eighteen had the Pi MM and two the Pi MS phenotype. Eight patients had evidence of KCS on Schirmer's tear testing. Ten patients achieved PC20 FEV1 in the methacholine inhalation test. All the patients had normal chest radiographs and all showed evidence of erosive arthropathy on hand radiographs. Five patients (25%) showed basal bronchiectasis and one mild interstitial lung disease on HRCT. All five patients with bronchiectasis had the Pi MM phenotype, four had HLA-DR4, four had KCS and three achieved PC20 FEV1; these values were not significantly different (p > 0.05) from those in patients without bronchiectasis. CONCLUSION: Using the highly sensitive technique of HRCT, we found evidence to suggest that the incidence of bronchiectasis in lifelong non-smoking RA patients may be much higher than previously reported. | |
| 8596144 | Herpes viruses in multicase families with rheumatoid arthritis. | 1995 Nov | OBJECTIVE: To investigate the rate and extent of infection by Epstein-Barr virus (EBV), cytomegalovirus, and herpesvirus 6 in families (affected and nonaffected members) with multiple cases of rheumatoid arthritis (RA). METHODS: Viral DNA was detected by polymerase chain amplification in cells from saliva and peripheral blood. Human leukocyte antigen pedigrees were characterized. RESULTS: Viral DNA, particularly EBV, was detected in increased frequency (p = 0.029) in the patients with RA compare to their nonaffected relatives. CONCLUSION: We suggest that in RA multicase families, increased frequency of viral infection is likely a consequence of the disease state and/or due to gene(s) as yet unidentified. | |
| 7731469 | [Chronic arthralgia: not a precursor of rheumatoid arthritis, but part of fibromyalgia syn | 1995 Apr 8 | OBJECTIVE: To determine the characteristics and the course of chronic arthralgia (CA) and the differences from newly diagnosed rheumatoid arthritis (RA). DESIGN: Retrospective, with a follow up after 2.5 years. SETTING: Outpatient clinic for rheumatology of the St. Antonius Hospital, Nieuwegein, The Netherlands. METHOD: The diagnosis of CA was made in the period of June 1986-December 1988 in 74 patients. The CA patients were sent a questionnaire after a mean of 2.5 years and invited for another rheumatological examination; 62 patients responded (84%). Data were compared with all 52 RA patients newly diagnosed in the same period by the same specialist. RESULTS: At the first visit CA had been present for 1 year, RA patients had had complaints for 0.6 years (p = 0.02). The RA patients had elevated BSE rates more often (31 vs. 8 mm in CA) (p < 0.0001) and more serious morning stiffness (75 vs. 0 minutes in CA) (p < 0.0001). The diagnosis of RA was made at the first visit in 86% and in 96% within half a year later. None of the CA patients developed an inflammatory joint disease within 2.5 years. In 1 out of 3 CA patients the diagnosis of fibromyalgia was made and more than 50% had complaints. CONCLUSIONS: CA for more than 3 years does not predict inflammatory rheumatic disease. In contrast, RA develops in a short period and the diagnosis is made in 96% within 1 year. CA can be considered a feature of the fibromyalgia syndrome. | |
| 7904455 | Lack of association between immunoglobulin light-chain constant- and variable-region polym | 1993 | Restriction fragment length polymorphisms (RFLPs) of C kappa, V kappa II, V lambda VII and VHIII genes were studied from a pool of 104 subjects with rheumatoid arthritis and 96 controls. There were no overall associations with either rheumatoid arthritis itself, or with HLA-DR4-positive and DR4-negative RA subgroups within rheumatoid subjects in this UK Caucasoid population. | |
| 7918716 | Cognitive-behavioral approaches to pain management in rheumatoid arthritis. | 1993 Dec | The purpose of this article is to review the literature on the topic of cognitive-behavioral approaches to pain management for persons with rheumatoid arthritis. Existing studies offer support for the usefulness of cognitive-behavioral techniques, but methodologic limitations were identified. Although the core element in rheumatoid arthritis pain management is optimal rheumatologic care, an important role also exists for strategies that seek to reduce the cognitive-evaluative aspects of arthritis pain. | |
| 7699618 | Endpoint measures in rheumatoid arthritis clinical trials: group summary and individual pa | 1994 Dec | OBJECTIVE: To evaluate the responsiveness of measures of disability, discomfort, and disease process in rheumatoid arthritis (RA) clinical trials, when used as group summary variables and as variables of individual patient improvement. METHODS: Disease outcome and process measures were assessed in 97 patients with RA of recent onset, who were participating in a prospective trial comparing the effectiveness of several drug treatment strategies. Measurements were done after 3 and 6 months of treatment. Group summary analysis was performed with tests of statistical significance of changes, and by calculating effect sizes (i.e., mean change in an endpoint divided by its standard deviation). Individual patient improvement was defined as improvement of > or = 33% compared to baseline, according to recommendations of the recently held Conference on Outcome Measures in Rheumatoid Arthritis Clinical Trials. RESULTS: Almost all mean group changes in endpoints were statistically significant (p < 0.001). Effect sizes and figures on individual patient improvement provided additional information: physical discomfort measures were rapidly responding measures that did not further improve after 3 months; disease process measures, joint count, erythrocyte sedimentation rate and C-reactive protein also responded quickly and kept improving up to 6 months; the disability measures were relatively unchanged at 3 months, and only the self-report questionnaire score showed considerable improvement at 6 months. CONCLUSION: Effect sizes and data on patients who showed clinical improvement in disease process or outcome measures offset the strongly significant p values of statistical tests for almost all endpoint measures. Although discomfort measures rapidly responded to therapy, disability and disease process measures may not reach optimal improvement within 6 months. | |
| 7835005 | Reduced sulphoxidation capacity in D-penicillamine induced myasthenia gravis. | 1994 Sep | Myasthenia gravis may be observed due to treatment with penicillamine (D-PA). The sulphoxidation capacity was measured in nine Swedish patients with rheumatoid arthritis (RA) who had developed myasthenia gravis toward D-PA. The results show that in eight of nine patients tested, this parameter was markedly reduced. A patient with poor sulphoxidation capacity has a twelve-fold greater risk of developing this rare side effect. The significance of this is discussed. | |
| 10163524 | Rheumatoid arthritis of the ankle: the role of total ankle arthroplasty. | 1995 Jul | The indications for total ankle replacement are limited to older patients with rheumatoid arthritis, especially those with multiple joint involvement and limited physical activity. The recommended surgical technique for total ankle arthroplasty includes an anterior surgical approach, minimal bone resection, and meticulous technique for cemented fixation of components. The results of published studies suggest total ankle arthroplasty should not be performed in patients who have had previous surgery on the ankle or foot, or who are younger than 57 years of age. | |
| 8014646 | Results of nonmetal-backed, high-density polyethylene, biconvex patellar prostheses. A 5-7 | 1994 Apr | This study evaluates the clinical and radiographic results of an all-polyethylene, biconvex, dome-shaped patellar prosthesis with precise instrumentation implanted in 53 knees with a minimum follow-up period of 5 years (average, 6.3 years; range, 5.0-7.1 years). The mean patient age was 70.9 years (range, 18.0-89.0 years). The mean Hospital for Special Surgery knee rating score was 63.6 before surgery and 83.4 after surgery. There was no fracture of the patella, no implant failure, or radiographic loosening of the prosthesis. Patellar complications consisted of two dislocations secondary to trauma and one case of patellar subluxation. Several radiographic parameters were measured. Means and SDs were computed for: (1) patellar tilt, as measured from a line between the anterior limits of the femoral condyles and the patella, which showed no significant difference after surgery (3.01 degrees +/- 5.12 degrees) compared to before surgery (3.73 degrees +/- 5.44 degrees); (2) the angle between the patellar component and the residual bone was -0.04 degrees +/- 2.04 degrees, with every case in the normal range (+/- 5 degrees); (3) there was no significant difference between pre- and postoperative patellar length, patellar thickness, or articular length of the patella; (4) the patellar height showed a small but statistically significant difference after surgery (2.69 +/- .64 cm) and before surgery (2.94 +/- .72 cm); (5) the distance from the tibial tubercle to the joint line did not differ significantly between preoperative (2.73 +/- 0.34 cm) and postoperative (3.06 +/- 0.36 cm) measurements; and (6) the distance from the center of the tibial plateau to the center line of the tibial prosthesis was 1.34 +/- 0.32 cm. These results are superior to previously reported series. | |
| 8843863 | Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease pro | 1996 Oct | OBJECTIVE: To establish that frequencies and levels of IgG antibodies to type II collagen are higher in early rheumatoid arthritis (RA), and to correlate these results with disease activity. METHODS: Forty-four patients were characterized as having early RA. Patient sera obtained at initial presentation and at 12 months were tested by enzyme-linked immunosorbent assay for IgG antibodies to native and denatured type II collagen. RESULTS: IgG antibodies to native and denatured type II collagen were detected at initial presentation in 27% and 82% of patients, respectively, and after 12 months in 14% and 50%, respectively. The presence of antibodies to native collagen was associated with activity of RA and severity of symptoms, and loss of antibodies at 12 months was associated with initially erosive RA and the DRB1 disease susceptibility motif. CONCLUSION: Levels of serum IgG antibodies to collagen in RA decrease over time and, therefore, are not attributable simply to cartilage destruction. The presence of early positivity for these antibodies, together with the RA susceptibility motif, appears to be predictive of rapidly progressive RA. | |
| 1388084 | Impaired suppressor cell activity due to surface sulphydryl oxidation in rheumatoid arthri | 1992 Sep | Rheumatoid arthritis is a chronic inflammatory disorder with considerable evidence of impaired regulation of the immune response, including defective suppressor cell function, especially in the synovial membrane. We have investigated whether oxidation of cell surface thiols might be responsible for these defects and whether such cell function may be modulated towards normal by treatment with a sulphydryl-reactive drug, D-penicillamine. Using healthy mononuclear cells treated with an impermeant thiol blocker, induction of suppressor activity by incubation with the lectin Con A was not dependent on surface sulphydryl groups but suppressor activity was abolished by thiol blockade after Con A stimulation. Peripheral blood mononuclear cells from patients with active rheumatoid disease showed impaired Con A-induced suppressor activity which was enhanced to near-normal levels by incubating the rheumatoid cells with a sulphydryl reducing agent, 2-mercaptoethanol, or D-penicillamine. Con A-stimulation of cells from patients treated with intramuscular gold or D-penicillamine generated more active suppression than those from patients receiving non-steroidal drugs only. Mononuclear cells from patients with other chronic inflammatory joint diseases showed normal Con A-induced suppressor activity. These data support the conclusion that surface thiols on mononuclear cells in rheumatoid arthritis are reversibly oxidized by the disease process. This gives rise to aberrant cell function including impaired suppressor activity. Such a mechanism may be at least partly responsible for the defective immunoregulation seen in rheumatoid patients and thus be a relevant target for thiol containing antirheumatic drugs. | |
| 7831322 | Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. | 1995 Jan 17 | Leukotriene B4 (LTB4) is a product of the 5-lipoxygenase pathway of arachidonic acid metabolism. LTB4 is a potent chemotactic factor for neutrophils and has been postulated to play an important role in a variety of pathological conditions including rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease. The role of LTB4 in such diseases has not yet been defined but in this paper we provide direct evidence that LTB4 plays a critical role in a murine model of RA. CP-105,696, (+)-1-(3S,4R)-[3-(4-phenylbenzyl)- 4-hydroxychroman-7-yl]cyclopentane carboxylic acid, is an LTB4 receptor antagonist that inhibits LTB4 binding to human neutrophil membranes with an IC50 of 3.7 nM and inhibits LTB4-induced chemotaxis of these cells with an IC50 of 5.2 nM. CP-105,696 inhibits LTB4-induced neutrophil influx in mouse skin when administered orally with an ED50 of 4.2 mg/kg. CP-105,696 had a dramatic effect on both the clinical symptoms and histological changes of murine collagen-induced arthritis when administered at doses of 0.3-10 mg/kg. Inhibition was not associated with suppression of the humoral immune response to collagen and was equally effective if drug treatment was commenced just prior to the onset of arthritis or throughout the experiment. These results suggest that LTB4 receptor antagonists may be effective therapeutic agents for the treatment of RA. | |
| 7839075 | Prevalence of antihuman parvovirus B19 IgG antibodies in patients with refractory rheumato | 1994 | We investigated the prevalence of antihuman parvovirus B19 immunoglobulin G (IgG) antibody in 108 Japanese patients with rheumatoid arthritis (RA) and 11 patients with polyarticular juvenile rheumatoid arthritis (JRA). Seropositivity of anti-B19 was significantly higher in patients with refractory RA (57.6%, 38/66) compared with patients with remittent RA (19.0%, 8/42; P < 0.001) or age-matched controls (24.3%, 19/78; P < 0.001). Patients with refractory polyarticular JRA had a significantly higher frequency of anti-B19 seropositivity (71.4%, 5/7) than age-matched controls (8.3%, 5/60; P < 0.001), while none of the remittent group was positive for the antibody (0/4). | |
| 8172576 | C1q in autoimmune diseases: rheumatoid arthritis. | 1993 Dec | Rheumatoid arthritis is an autoimmune disease involving stimulation of T cells and the production of autoantibodies. In this disease autoantibodies to collagen type II are believed to play a major role in inflammatory events ultimately resulting in joint destruction. However, collagen type II-containing cartilage has been discussed as one of the primary antigens (as evidenced by animal models), despite not being accessible. Evidence is presented here for the involvement of C1q, the collagen-like subunit of the first component of complement, in the pathogenesis of rheumatoid arthritis. The C1q A-chain contains an epitope exhibiting an identical sequence to part of an arthritis modulating epitope from collagen type II. Furthermore, preapplication of a synthetic peptide, representing the epitope on the C1q A-chain, has been shown to delay the onset and reduce the severity of collagen-induced arthritis in a DBA/1 mouse model. Since the complement system, in particular C1q (as part of the first component of the classical pathway), plays a major role in the inflammatory process, we propose that the collagen-like C1q molecule, altered during the inflammatory process, may result in the generation of autoantibodies which also recognize collagen type II, and may thus be considered as a link between the early inflammatory process in the joint and the only later occurring cartilage destruction. | |
| 7627266 | Exacerbation of rheumatoid arthritis after removal of adrenal adenoma in Cushing's syndrom | 1995 Apr | A 46-year-old woman with rheumatoid arthritis had been on non-steroidal antiinflammatory agents for eighteen years until she developed cushingoid features and hypertension resistant to antihypertensive drugs. She had high plasma cortisol and 24 h urinary 17-hydroxycorticosteroids (17HCS) which were not suppressed by 8 mg dexamethasone per day for two days. The circadian rhythm of plasma cortisol was absent and plasma ACTH concentrations were suppressed before and after intravenous administration of CRH. Abdominal computed tomography demonstrated a tumor (3.0 x 3.0 x 2.3 cm) in the right adrenal gland and a 131I-6 beta-19-nor-methylcholesterol scan revealed marked uptake on the same side. The patient underwent a right adrenalectomy and the diagnosis of a cortisol secreting benign adenoma was histologically confirmed. Blood pressure declined and cushingoid features regressed, but three months after the operation and while the patient was on replacement, she complained of pain on motion, marked tenderness and swelling of fingers, wrists, elbows, knees and foot joints, and had very high rheumatoid factors. Treatment with immunosuppressive drugs and oral and intraarticular administration of glucocorticoids were necessary to relieve the clinical symptoms of rheumatoid arthritis. In summary, we report a patient with rheumatoid arthritis and Cushing's syndrome due to an adrenal adenoma, in whom rheumatoid arthritis was exacerbated after curing the Cushing's syndrome. This suggests that it is imperative to follow the development and/or course of autoimmune diseases after the treatment of Cushing's syndrome. | |
| 7552073 | Hypoxia, oxidative stress and rheumatoid arthritis. | 1995 Apr | The synovial cavity has a negative pressure in health. When the joint is exercised, vascular patency is maintained, allowing for nutrition of the avascular cartilage. In rheumatoid synovitis, the situation is altered. The cavity pressure is raised and upon movement this pressure exceeds the capillary perfusion pressure, causing collapse of the blood vessels. This leads to the production of multiple episodes of 'hypoxic-reperfusion injury' generating reactive oxygen species (ROS). Such ROS oxidise: (a) IgG, inducing rheumatoid factor production (b) Hyaluronan, leading to hyaluronan fragmentation products which may alter immune function (c) Lipids, generating aldehydes which are toxic and may alter T cell/macrophage interactions (d) lipoproteins, leading to the production of monocyte chemotactic peptides Progressive hypoxia alters immune function, predominantly by calcium mediated pathways. | |
| 1632660 | Pathogenic importance of fibronectin in the superficial region of articular cartilage as a | 1992 Jul | To identify the local factors in cartilage that are responsible for the induction of pannus invasion, a 14 day organ culture study in which rheumatoid synovium was grown in contact with cartilage pieces was carried out. Rheumatoid synovium preferentially extended over hyaluronidase treated cartilage pieces, but detached from untreated pieces. Rheumatoid synovium extended over hyaluronidase treated cartilage surfaces containing fibronectin more extensively than over surfaces treated with hyaluronidase only. Extension over hyaluronidase treated cartilage surfaces containing immune complexes was small. The adherence of synovial cells to hyaluronidase treated cartilage slices in vitro was specifically inhibited by the synthetic peptide, Gly-Arg-Gly-Asp-Ser-Pro, which is the adhesive portion of the fibronectin molecule. Furthermore, synovial fibroblast-like cellular extension, morphologically similar to rheumatoid pannus, was observed in the organ culture experiments in which rheumatoid synovium grew over hyaluronidase treated cartilage surfaces containing fibronectin. Synovial tissue extension over fibronectin coated surfaces was inhibited when hyaluronic acid and chondroitin-4-sulphate, major components of cartilage proteoglycans, were present on the cartilage surface. These findings suggest that fibronectin present in the superficial region of cartilage potentiates rheumatoid synovial extension and proteoglycans and immune complexes inhibit rheumatoid synovial extension. It is likely that fibronectin deposited on the eroded surface of articular cartilage induces pannus formation in rheumatoid arthritis. | |
| 8474071 | Synovial type (group II) phospholipase A2 in cartilage. | 1993 Feb | Phospholipase A2 (PLA2) was produced in E. coli by a recombinant technique using a synthetic gene coding for PLA2 found in synovial fluid (SF) of patients suffering from rheumatoid arthritis (RA). Polyclonal antibodies were produced against the recombinant synovial type PLA2 (syn-PLA2) in a rabbit. The IgG fraction of the antiserum was isolated and the specificity was tested by immunoblotting. The antiserum detected a protein with an apparent molecular weight of 15 kDa in extracts of cartilage, but did not react with PLA2 isolated from human pancreas or ascitic fluid. In immunohistochemistry, the anti-syn-PLA2 antibody decorated chondrocytes and matrix of articular, laryngeal and auricular cartilage, but did not decorate synovial tissue or its contained inflammatory cells in RA or other human tissues tested (pancreas, liver, thyroid, tonsil, lung, nasal polyp, skin, placenta, myometrium, bone). The results show that syn-PLA2 is present both in articular and extraarticular cartilage and support the view that PLA2 found in SF might originate from chondrocytes, and not from synovial lining or inflammatory cells. | |
| 1391564 | [Lymphoproliferative syndromes associated with rheumatoid arthritis]. | 1992 Aug | Rheumatoid arthritis predispose to several lymphoproliferative syndromes, some of them are of doubtful neoplastic type, as the lymphoproliferative disease of granular lymphocytes, whereas others are clearly malignant, as non-Hodgkin's lymphomas and multiple myeloma. In this paper, we review the potential etiological agents, mainly the reduction of the "natural killer" activity and immunity disorders against virical oncogenes. The onset of monoclonal gammopathy in rheumatoid patients is also stressed, due to its potential prognosis value in the development of lymphoid neoplasias. | |
| 1596698 | Susceptibility of normal and arthritic human articular cartilage to degradative stimuli. | 1992 Jun | Recombinant interleukin-1 (IL-1) alpha and beta stimulated significant loss of glycosaminoglcan (GAG) content from normal (non-arthritic) articular cartilage explants but only after incubation for 14 days and only in specimens from 8/21 (38%) individuals. By contrast, all cartilage specimens but one from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were degraded (as judged by their reduced GAG content) by the recombinant cytokines but again only after 14 days' incubation. The reduction in GAG induced by IL-1 was also greater for both OA and RA cartilage than normal cartilage. Synovial fluids (SFs) from RA patients stimulated greater loss of GAG content from OA cartilage explants than normal explants although in both cases the loss was evident within 2 days. It is concluded that cartilage explants from some individuals are susceptible to the degradative effects of IL-1 whereas others are refractory and that arthritic cartilage is more susceptible to degradation by both IL-1 and RA SFs than non-arthritic cartilage. |