Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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1338503 | [Dot immunobinding assay in detection of IgE-type rheumatoid factor]. | 1992 Oct | The sera from 86 patients with autoimmune diseases, 31 atopic and 65 healthy blood donors were detected for IgE type rheumatoid factor (IgE-RF) by using anti-human IgE monoclonal antibody and dot immunobinding assay. The positive frequency and mean value of IgE-RF in patients with autoimmune diseases were significantly higher than those in the other groups. IgE-RF was positive in 19/37 cases of rheumatoid arthritis (RA), 6/18 systemic lupus erythematosus and 13/31 primary Sjogren's syndrome, with mean values of 23.1, 12.1 and 26.9 ng/ml respectively. 75% RA patients with IgM-RF (+) had IgE-RF, with a mean value of 27.0 ng/ml, whereas 33% of those with IgM-RF (-) had IgE-RF with a mean value of 16.5 ng/ml. In contrast, only 2/31 atopic and 6/65 healthy blood donors had positive IgE-RF with mean values of 3.7 and 6.1 ng/ml respectively. Hence, IgE-RF is helpful not only in raising the sensitivity of RA diagnosis, but also in distinguishing autoimmune diseases from allergy. | |
8856613 | V beta 17 T cell receptor peptide vaccination in rheumatoid arthritis: results of phase I | 1996 Aug | OBJECTIVE: To determine whether modulation of activated T cells occurs in patients with rheumatoid arthritis (RA) after immunization with T cell receptor (TCR) V beta 17 peptides, a phase I trial was initiated to investigate the safety and feasibility of TCR peptide immunization as a therapeutic approach in RA. METHODS: 15 patients with moderate to severe RA were given an intramuscular injection of one of 4 doses (10, 30, 100, and 300 micrograms) of the V beta 17 peptide vaccination, followed by a booster injection of the same dose of vaccine 3 weeks later. Patients were followed for 48 weeks. RESULTS: The product was well tolerated and no serious adverse events attributable to the vaccine were observed. This was an uncontrolled phase I trial, however; decreases in patients joint scores were observed at all followup visits starting at 4 weeks after primary immunization. Activated V beta 17 T cells (IL-2R+) in peripheral blood were decreased (> or = 20%) in 3/5 patients in the 100 micrograms group after initial measurement at Week 2 and 3/4 patients in the 300 micrograms group 3 weeks after immunization. Lymphocyte proliferation in response to the V beta 17 peptide was detected at 6 weeks or later after primary inoculation in 6/15 patients (40%) immunized. CONCLUSION: Further controlled studies are required to assess the biologic and clinical efficacy of this treatment approach. | |
1285884 | Pregnancy and rheumatoid arthritis: an overview. | 1992 Oct | The literature concerning the relationship of rheumatoid arthritis (RA) to pregnancy is reviewed. The amelioration of RA during pregnancy is a complex process. No specific factor that causes amelioration and is amenable to therapeutic intervention has been identified. Either RA is associated with lower fertility/fecundity, or pregnancy induces a protective effect against the development of the disease. The biological mechanism of these findings is not established. | |
7748021 | Antibody to Mycobacterium tuberculosis 65 kDa heat shock protein in patients with rheumato | 1995 Mar | OBJECTIVE: To clarify the significance of the humoral immune response triggered by the Mycobacterium tuberculosis (M.tb) 65 kDa heat shock protein (hsp) in the pathogenesis of rheumatoid arthritis (RA). METHODS: M.tb 65 kDa hsp-specific IgG, IgA, IgM, and IgG subclass antibodies in serum or synovial fluid (SF) of RA and other disease patients were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: RA patients did not show any characteristic increase in mycobacterial 65 kDa hsp-specific antibodies compared with healthy individuals. In contrast, antigen-specific IgG and IgG2 antibody titres in the serum of RA patients were significantly lower than those of patients with tuberculosis and normal controls. In addition, there was also no significant difference in antibody titre between the serum and SF of RA patients, nor was any significant difference found between the SF of RA and Reiter's patients. CONCLUSION: The failure to detect a significant increase in IgG anti-M.tb 65 kDa hsp antibodies in RA patients does not exclude the possibility of microbial immunity in the aetiology of RA. Nevertheless, anti-M.tb 65 kDa hsp antibodies clearly do not appear to be the disease specific markers for RA and their relatively reduced concentrations may argue against their playing a major role in the disease pathogenesis. | |
7793234 | Associated autoimmune diseases in myasthenia gravis. A population-based study. | 1995 Mar | During a comprehensive epidemiological study of myasthenia gravis (MG) in Western Denmark 1975-1989, we analyzed the occurrence, clinical characteristics and prognosis of associated autoimmune diseases (AAD) in MG patients. AAD were found in 20 of 212 incident cases (9%) and in 30 of 220 prevalent cases (14%). The most common diseases were: thyroid disorders and rheumatic arthritis. Clinically, it was not possible to identify a subgroup of MG patients with a higher risk of AAD. In most MG patients the AAD occurred before thymectomy. The severity of the AAD was not influenced by thymectomy. The remission rate was lower in MG patients with AAD than in MG patients without AAD suggesting that the autoimmune response in MG patients with AAD is more severe. | |
8527017 | Slow-acting antirheumatic drugs. Drug interactions of clinical significance. | 1995 Jul | The slow-acting antirheumatic drugs (SAARDs) are being used in an increasing proportion of patients with rheumatoid arthritis (RA). The potential toxicity of each drug is well recognised. Many patients with RA will be on other medications and the potential for adverse drug interactions with SAARDs is not so well publicised. There have, over the years, been numerous reports of possible drug interactions with SAARDs but few of these are clinically relevant. It is, however, vitally important that the physician is aware of a number of potentially life-threatening interactions, particularly those associated with methotrexate. The SAARDs are a very useful group of drugs for the treatment of RA and, by being aware of their potential toxicity and drug interactions, hopefully they can be used safely and effectively. | |
8734713 | Radiographic changes in the temporomandibular joint in patients with generalized osteoarth | 1996 May | This is the first study concerned with radiographic characteristics in patients with generalized osteoarthritis and signs and symptoms of temporomandibular joint involvement. For comparison, patients with rheumatoid arthritis and temporomandibular joint involvement were used. The patient material comprised 20 patients with generalized osteoarthritis (20 joints) and 21 patients with rheumatoid arthritis (21 joints). The radiographic methods were corrected sagittal tomography (hard tissue changes, joint space, and condylar position), frontal tomography (hard tissue changes), and individualized oblique lateral transcranial projections (condylar translation). Sixteen (80%) joints in the group of patients with generalized osteoarthritis and 15 (71%) joints in the group with rheumatoid arthritis revealed structural changes. The condyle was the predominant location. No radiographic criterion was pathognomonic for generalized osteoarthritis or rheumatoid arthritis. However, osteophytes, flattening of the condyle, or a reduced joint space was observed more often in joints with generalized osteoarthritis, whereas erosions in the condyle were more common in joints with rheumatoid arthritis. The radiographic findings in patients with generalized osteoarthritis are more similar to those seen in patients who have the common form of temporomandibular joint osteoarthritis than to those in patients with rheumatoid arthritis. | |
7542201 | Expression and functional significance of an activation-dependent epitope of the beta 1 in | 1995 Jun | The avidity of VLA integrins for their ligands can be increased by their transition to an active conformational state. This conformational change can be detected with a novel monoclonal antibody (mAb), termed 15/7, that recognizes an activation-dependent conformational epitope on the common beta 1 polypeptide of different VLA alpha beta 1 integrins. In an attempt to understand the possible role of the active conformational state of beta 1 integrins in vivo, we first investigated the expression of 15/7 epitope on T lymphocytes from patients with chronic inflammatory joint diseases. An enhanced expression of the 15/7 epitope was found in the synovial fluid (SF) T lymphocytes from these patients as compared to their peripheral blood (PB) T cells. The effect of different cytokines on the appearance of the 15/7 activation epitope in PB T lymphocytes was subsequently analyzed; interferon-gamma, interleukin-2 and, to a lower extent, tumor necrosis factor-alpha were able to induce an increased expression of the 15/7 epitope. This enhanced 15/7 expression correlated with a higher binding ability to fibronectin of cytokine-activated T cells. The presence of this activation epitope was detected in a small proportion of T lymphocytes scattered within inflammatory foci of synovial membrane from rheumatoid arthritis and thyroid glands from Hashimoto's chronic thyroiditis. We then analyzed the possible role of 15/7 epitope expression on cell adhesion in vitro. Immunofluorescence studies showed that the 15/7 epitope displayed a spot-like distribution, selectively decorating adhesive contacts of U-937 myelomonocytic cells attached to the 80 kDa proteolytic fragment of fibronectin (FN80). Furthermore, the anti-beta 1 15/7 mAb was able to induce both T lymphocyte, Jurkat and U-937 cellular binding and spreading on FN80. Altogether these results indicate that an activated conformation of beta 1 integrins is detected in vivo in lymphocyte infiltrates from chronic inflammatory conditions. The active conformations of beta 1 integrins are regulated by physiologic mediators such as cytokines, play an important role in cellular attachment and spreading, and appear to be involved in the development of inflammatory processes. | |
7492220 | Use of high resolution computed tomography of the lungs in patients with rheumatoid arthri | 1995 Oct | OBJECTIVE: To assess the usefulness of high resolution computed tomography (HRCT) of the lungs in patients with rheumatoid arthritis (RA) with and without respiratory symptoms. PATIENTS AND METHODS: Eighty eight RA patients with a mean duration of disease 12 (SD 8) years were evaluated. Eleven patients were excluded because of previous exposure to silica. The 77 remaining patients formed two groups according to the absence (group I, n = 38) or the presence (group II, n = 39) of chronic respiratory symptoms. A control group consisted of 51 non-smoking, healthy patients. RESULTS: The most frequent abnormalities observed in the 77 RA patients were bronchiectasis or bronchiolectasis (n = 23, 30%), pulmonary nodules (n = 17, 22%), subpleural micronodules or pseudoplaques (n = 13, 17%), ground glass opacities (n = 11, 14%), and honeycombing (n = 8, 10%). Bronchiectasis or bronchiolectasis (p = 0.012), rounded opacities (p = 0.016), ground glass attenuation (p = 0.004), and honeycombing (p = 0.002) were found more often in RA group II (with respiratory symptoms) than in group I (no respiratory symptoms). Non-linear septal opacities were more frequent in group I than in the control group, but other HRCT findings did not differ statistically significantly between group I and the control group. CONCLUSION: Bronchiectasis may be a characteristic lung change in RA patients. Abnormalities on HRCT are less frequently observed in the absence of respiratory symptoms than in the presence of such symptoms (29% versus 69%). | |
7561066 | Growth-related gene product alpha. A chemotactic cytokine for neutrophils in rheumatoid ar | 1995 Oct 1 | Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI 1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-alpha (mean 1.3 +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/- 0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro alpha plays an important role in the ingress of PMNs into the RA joint. | |
8165874 | [Color Doppler study in patients with rheumatoid arthritis and scleroderma]. | 1994 Jan | In a case of RA the synovitis and the pannus can be examined using ultrasound. The activity of the condition registers as a halo around the flexor tendons of the fingers which sends off fewer echoes. Peripheral resistance (expressed in terms of Pourcelot's ratio) falls where clinical activity in the joints is higher. Correspondingly, values of Pourcelot's ratio are normal or higher than usual in the case of inactive joint processes. Diagnostic signs for PSS are very high values of Pourcelot's ratio and a closed "systolic window". After the hands have been warmed (for 5 min in a bath of water at 40 degrees C) the systolic window is "opened" in cases of a functional disruption in the blood supply, whereas in cases of advanced PSS the blood vessels are observed to be rigid with high peripheral resistance. | |
1622411 | Glucocorticoid receptors in rheumatoid arthritis. | 1992 Jul | OBJECTIVE: Increasing evidence suggests that there is a close interrelationship between the immune system and the hypothalamic-pituitary-adrenal axis. One way these systems are linked is through specific receptor proteins for glucocorticoid hormones in lymphocytes. We sought to determine whether the levels of these receptors differ in patients with rheumatoid arthritis (RA), compared with levels in healthy subjects. METHODS: We determined the density and affinity of lymphocyte glucocorticoid receptors, as well as basal cortisol levels, in 90 patients with active RA and in 200 healthy controls, using a whole cell binding assay. RESULTS: The number of glucocorticoid receptors in RA patients was significantly lower than in controls (mean +/- SD 2,144 +/- 500 per cell versus 5,619 +/- 1,373 per cell; P less than 0.001), whereas there were no differences in binding affinity or cortisol levels. Glucocorticoid receptor density did not correlate with inflammatory disease activity. CONCLUSION: Since glucocorticoids are potent immunosuppressive agents, the decrease in their receptors suggests an impairment of the immune-hypothalamic-pituitary-adrenal axis in patients with RA. | |
8833058 | Efficacy of triple DMARD therapy in patients with RA with suboptimal response to methotrex | 1996 Mar | Rheumatoid arthritis (RA) has a profound effect on patients, producing significant morbidity and in some cases mortality. Because of this, most rheumatologists are moving to disease modifying antirheumatic drug (DMARD) therapy earlier in the course of RA. Methotrexate (MTX) has become the initial DMARD of choice for most rheumatologists. Unfortunately, treatment of RA with a single DMARD, including MTX, often results in a suboptimal response. Therefore, most rheumatologists are now using combinations of DMARD to treat patients with RA who have had incomplete responses to single DMARD therapy. The Rheumatoid Arthritis Investigational Network (RAIN) reported the results of a double blind, controlled comparison of triple drug therapy (MTX-sulfasalazine-hydroxychloroquine) against MTX alone, and against the combination of hydroxychloroquine and sulfasalazine. Twenty-eight patients who had suboptimal responses to MTX or the combination of sulfasalazine and hydroxychloroquine were then treated with triple therapy in an open label study. Fourteen had previously failed MTX therapy, and 14 had previously failed combination therapy with sulfasalazine and hydroxychloroquine. Both groups had statistically significant improvements in sedimentation rates, morning stiffness, swollen joint scores, tender joint scores, patient global status assessment, and physician global status assessment. Statistical significance was reached for all these variables for patients in both groups, but improvement was greater for the patients in the sulfasalazine-hydroxychloroquine group. Patients with RA who have had suboptimal responses to MTX, or to the combination of sulfasalazine-hydroxychloroquine, show both statistical and clinically significant improvement in multiple clinical variables when treated with the combination of MTX 17.5 mg/week, sulfasalazine 500 mg bid, and hydroxychloroquine 200 mg bid. | |
8257207 | Gadolinium-DTPA enhanced magnetic resonance imaging of bone cysts in patients with rheumat | 1993 Oct | OBJECTIVES: To examine the contents of intraosseous cysts in patients with rheumatoid arthritis (RA) through the signal intensity characteristics on gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging. METHODS: The hand or foot joints of nine patients with the cystic form of RA (where the initial radiological abnormality consisted of intraosseous cysts without erosions) were imaged before and after intravenous administration of Gd-DTPA. A 0.6 unit, T1 weighted spin echo and T2* weighted gradient echo were used to obtain images in at least two perpendicular planes. RESULTS: Most cysts showed a low signal intensity on the non-enhanced T1 weighted (spin echo) images and a high signal intensity on the T2* weighted (gradient echo) images, consistent with a fluid content. No cyst showed an enhancement of signal intensity on the T1 weighted images after intravenous administration of Gd-DTPA, whereas synovium hyperplasia at the site of bony erosions did show an increased signal intensity after Gd-DTPA. Magnetic resonance imaging detected more cysts (as small as 2 mm) than plain films, and the cysts were located truly intraosseously. In six patients no other joint abnormalities were identified by magnetic resonance imaging; the three other patients also showed, after Gd-DTPA administration, an enhanced synovium at the site of bony erosions. CONCLUSIONS: It is suggested that intraosseous bone cysts in patients with RA do not contain hyperaemic synovial proliferation. The bone cysts in patients with the cystic form of RA may be the only joint abnormality. | |
7634727 | Spinal disease in the aged. | 1995 Jul | Treatment of the diseased spine in the elderly is a difficult challenge for the practitioner. Spinal surgery for this population requires specialized surgical skills. Patient evaluation, nonoperative treatment, surgical indications, surgical techniques, and postoperative management involve unique considerations. The patient's functional expectations, general medical condition, and proposed benefits from surgery must be addressed before any surgical intervention. Spinal surgery for the aged requires the orthopaedic surgeon to consider this patient as more than just an older individual and demands that the entire perioperative milieu be examined and its issues resolved. The projected data on aging of the United States population make this issue increasingly important. | |
7537341 | [Involvement of substance P in gastric mucosal lesions of patients with rheumatoid arthrit | 1995 Mar | We investigated the relation between gastric mucosal lesions and substance P (SP) in 64 patients with rheumatoid arthritis (RA) taking nonsteroidal antiinflammatory drugs (NSAIDs). In these patients, the incidence of gastric mucosal lesions was as high as 53.1%. Serum SP levels were significantly higher in patients with gastric mucosal lesions than in those without gastric lesions. Erythrocyte sedimentation rate, serum C-reactive protein and rheumatoid factor (RF) levels were also higher in patients with gastric mucosal lesions. A positive correlation between serum SP and RF levels was found in patients with RA. Experimental gastric mucosal lesions induced by an oral administration of indomethacin in rats were significantly enhanced by an additional intraperitoneal injection of SP. From these observations, it is suggested that, in addition to the effect of NSAIDs, SP elevation in blood has a role in the development of gastric mucosal lesion in patients with RA. | |
1606725 | Lymphocytes from patients with rheumatoid arthritis produce agalactosylated IgG in vitro. | 1992 Jun | The percentage of oligosaccharide chains lacking galactose was measured in IgG obtained from pokeweed mitogen-activated cultures of blood lymphocytes from patients with rheumatoid arthritis and controls. Secreted IgG from rheumatoid arthritis lymphocytes was deficient in galactose compared with IgG from the lymphocytes of controls. This confirms that agalactosylation is a significant feature of the disease and demonstrates that it can occur at the B cell level and is not merely a post-secretory event. | |
8854485 | [Arthroscopic surgery of the knee with CO2 laser surgery of the knee]. | 1996 Aug | We present a preliminary report of our experience with the CO2 laser in arthroscopic surgery of the knee. Between August '94 and February '95 a total of 27 knee arthroscopies were done with the Sarplan 1030 30-watt CO2 laser for various knee problems, mostly degenerative arthritis. Complications such as subcutaneous emphysema and reactive effusion were noted, but no other significant problems. Although the arthroscopies were performed in a CO2 medium, which created some technical difficulties, the CO2 laser was very effective in neatly shaving the degenerative, articular cartilage, and in meniscal debridement. With the laser probe, some areas of the knee joint previously not accessible, can be reached and treated. Our impression is that with proper indications, laser arthroscopy has some advantages over traditional arthroscopy. Further technical improvement is needed before it is introduced for routine use. | |
7826823 | The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and syno | 1994 Sep | 1. A sensitive, stereospecific assay using gas chromatography-mass spectrometry (GC/MS) was established to measure the concentrations of the enantiomers of ibuprofen in small volumes (50 microliters) of blister fluid. 2. The concentrations of the enantiomers in blister fluid, assessed in eight patients, were similar to those in synovial fluid, both fluids behaving as peripheral compartments with respect to plasma. 3. The mean rate constants of transfer of R-ibuprofen into (0.14 +/- 0.06 h-1) and out of (0.20 +/- 0.04 h-1) blister fluid were not significantly different from those for synovial fluid (0.19 +/- 0.12 h-1, 0.34 +/- 0.11 h-1, respectively). Similarly, the mean rate constants of transfer of S-ibuprofen into (0.22 +/- 0.07 h-1) and out of (0.27 +/- 0.08 h-1) blister fluid were not significantly different from those for synovial fluid (0.29 +/- 0.10, 0.36 +/- 0.11 h-1). However, the correlations were poor between the transfer constants for each of the enantiomers between plasma, and both blister and synovial fluid (P > 0.2). 4. The complex rate constant of transfer of S-ibuprofen into blister fluid (0.22 +/- 0.07 h-1) was greater than that of R-ibuprofen (0.14 +/- 0.07 h-1), which may be explained by the lesser protein binding of the S-enantiomer.(ABSTRACT TRUNCATED AT 250 WORDS) | |
9097770 | The management of corneal perforations associated with rheumatoid arthritis. An analysis o | 1995 Sep | BACKGROUND: Sterile corneal ulceration is a rare complication of rheumatoid arthritis and may lead to corneal perforation. Surgical management for visual restoration frequently is unsuccessful. The authors analyze the factors that may determine the failure of corneal surgery in perforations associated with rheumatoid arthritis. METHOD: The management of 29 patients with rheumatoid arthritis with corneal perforations requiring surgical intervention was reviewed. The corneal lesions were classified either as necrotizing keratitis (n = 20) or as ulcers secondary to surface disease (n = 12), depending on the most evident primary pathology. The outcome of different methods for primary repair (i.e., application of tissue adhesive, lamellar graft, or penetrating keratoplasty) and graft survival in penetrating keratoplasties were analyzed. RESULTS: Fifty-seven corneal procedures were performed in 32 eyes. Primary repair was successful (i.e., no further corneal surgery within 6 months was required) in five eyes (25%) with necrotizing keratitis and in eight eyes (67%) with perforations secondary to surface disease. The application of tissue adhesive, when planned as long-term treatment, was unsuccessful in all five eyes. Immunosuppression significantly improved the survival of first penetrating grafts (42% graft survival after 1 year versus 11% without immunosuppression, P = 0.02). Of 25 graft failures, 20 (80%) were caused by recurrent melts up to 6 months after penetrating keratoplasty. Ocular surface infection was responsible for failure in six of ten grafts after that time. CONCLUSION: Complications of corneal surgery in rheumatoid corneal perforations are frequent. The type of surgical procedure, the predominant pathogenic mechanism, and the perioperative immune status influence the outcome. The control of corneal melting and the prevention of surface infection are critical for graft survival. |