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

ID PMID Title PublicationDate abstract
1318122 Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis. 1992 Jan Two types of tumor necrosis factor receptors have been characterized, both capable of transmitting the signal and exerting the biological functions of TNF and lymphotoxin. We measured the plasma concentrations of two types of TNF binding proteins (sTNFR-A and sTNFR-B) in patients with rheumatoid arthritis (RA) and spondylarthropathies (SpA) using an enzyme-linked binding assay. In normal controls (n = 43), mean plasma concentrations were 1030 +/- 55 and 1461 +/- 59 pg/ml for sTNFR types A and B, respectively. In 67 patients with moderate RA, mean levels were 1422 +/- 82 pg/ml (type A) and 2088 +/- 109 pg/ml (type B); in 34 patients with severe RA, 2588 +/- 279 pg/ml and 4494 +/- 550 pg/ml, respectively, were measured (P less than 0.0001 compared to normal controls). Concentrations of both type A and type B sTNFR were highly correlated in severe RA (R2 = 0.7) but not in SpA or normal controls. T lymphocytes in synovial fluid of patients with RA expressed predominantly type A TNF receptors on their surface; in some patients a weaker expression of type B receptors was also detectable. Soluble TNF binding proteins in patients with RA were able to neutralize TNF in a cytotoxicity assay, demonstrating their ability to act as "TNF-inhibiting factors". We conclude that both types of TNF receptors are parameters of disease activity in RA and may also act as TNF antagonists.
1598495 The influence of synovial fibroblasts on the phagocytosis of Staphylococcus by polymorphon 1992 It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanism that contribute to the increased susceptibility of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surface on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMN may lead to reduced clearance of bacteria from the joint.
7648235 Development and preliminary assessment of a simple measure of overall status in rheumatoid 1995 Jun We describe the development and initial assessment of a simple measure of overall status in rheumatoid arthritis (OSRA) for use in the routine clinical setting. The measure is constructed in four parts: demographic details, activity score, damage score and treatment category. It requires no laboratory tests and uses details collected routinely during a clinic visit. It was validated in a series of 488 patients. The measure proved acceptable and demonstrated face, content, construct and discriminant validity. OSRA will be useful as an audit tool in the serial follow-up of RA patients and in describing the characteristics of a population of such patients.
8275592 Iliopsoas bursitis in rheumatoid arthritis. 1993 Sep A 58-year-old woman with rheumatoid arthritis (RA) presented with persistent hip pain and an inguinal mass. Considerable liquid had collected inside the iliopsoas bursa, apparently not in communication with the hip joint, as shown by ultrasonography and computed tomography (CT). After one month of systemic steroidal therapy (25 mg/day prednisone), the palpable inguinal mass and pain had disappeared. Iliopsoas bursitis should be suspected in RA patients with a long history of disease presenting with an inguinal mass, persistent groin pain or unilateral leg swelling. The lack of communication between the hip joint cavity and bursa may be considered as a favourable prognostic index. Steroid treatment should be always attempted in order to avoid surgery.
7799362 The challenge of sensorineural hearing loss in rheumatoid arthritis. 1994 Sep Patients with rheumatoid arthritis are exposed to a variety of pharmacologic agents capable of causing sensorineural hearing loss. We describe such a patient who was eventually found to have an acoustic neuroma. The case illustrates the difficulty of diagnosing acoustic neuroma and the need for a high index of suspicion when unilateral hearing loss is detected. The evaluation of patients with sensorineural hearing loss is discussed.
10147569 Double-stem silicone implant arthroplasty of all metatarsophalangeal joints in patients wi 1992 Jan Double-stem silicone implants have been used to reconstruct destroyed hallux metatarsophalangeal joints (MTPJ) for many years. When smaller implants became available, they were used to reconstruct the lateral four MTPJ. An arthroplasty of all MTPJ was performed using these implants in 44 patients (72 feet) with rheumatoid arthritis (RA). The mean age of patients was 46 years (range, 21 to 66) and 84% were female. Previous surgery had been performed on 28% of the feet. All patients were followed prospectively for an average of 67 months (range, 36 to 111). The patients were evaluated clinically and radiographically; results were recorded on a standardized foot form that allowed computer analysis of the data. The results showed improvement in the hallux valgus angle from 41.6 degrees to 16.1 degrees postoperatively, with no loss of correction over time. Similarly, other forefoot deformities, such as plantar callus and lateral toe abnormalities, all improved both clinically and radiographically. The pain, walking, and function scores all improved, with the greatest improvement being pain relief. Radiographic analysis showed some evidence of fracture in seven hallux (9.7%) and nine lateral toe (3%) implants. Only three toes with implant fracture had some pain at follow-up examination. Three other lateral toe implants were removed for pain. There was no evidence of deep infection or silicone synovitis. Other complications included superficial infection, delayed wound healing, and second surgery for heterotopic bone excision.(ABSTRACT TRUNCATED AT 250 WORDS)
1472120 Activation of gold-reactive T lymphocytes in rheumatoid arthritis patients treated with go 1992 Dec OBJECTIVE: To assess the role of T lymphocyte sensitization in the etiology of side effects of gold therapy in patients with rheumatoid arthritis (RA). METHODS: Lymphocyte proliferation induced by gold(III) and gold(I) salts was measured in 53 subjects: 30 RA patients with gold-induced side effects (17 with dermatitis, 9 with proteinuria, 3 with hematologic complications, and 1 with colitis), 9 RA patients without side effects despite prolonged chrysotherapy, 4 RA patients who had never received gold, and 10 healthy controls. Peripheral blood lymphocytes were cultured with the different gold salts and proliferation was measured by 3H-thymidine incorporation. RESULTS: Thirteen of the 17 RA patients who developed gold-induced dermatitis showed significant T lymphocyte proliferation in response to gold(III) salts, and this proliferation could be completely blocked by monoclonal antibodies directed at the HLA-DR molecule. Such proliferative responses were not seen in patients with other gold-induced side effects, in patients who had never received gold, or in healthy controls. Only 1 of 9 patients who had not developed side effects despite long-term maintenance chrysotherapy showed significant lymphocyte activation with gold(III) salts. Lymphocyte proliferation could not be induced with gold(I) salts or with other metal salts. CONCLUSION: Patients with RA who develop dermatitis following treatment with sodium aurothiomalate [gold(I)] have T cells which proliferate in an HLA-DR-restricted manner in response to HAuCl4 [gold(III)]. We believe this observation can lead to more accurate diagnosis and treatment of side effects, which currently limit the use of one of the most effective antirheumatic drugs.
7750887 [Innovative approaches in therapy of chronic polyarthritis]. 1995 Mar 10 New approaches to the treatment of chronic polyarthritis are based on recent insights into the pathogenesis of this disease, in particular the involvement of cytokines and adhesion molecules in the process of joint destruction. These experimental approaches have been made possible by the development of monoclonal antibodies and recombinant fusion proteins, with the aid of which, cytokines such as TNF-alpha or IL-6 can be neutralized, or adhesion molecules and receptors on the cell surface blocked. Other therapeutic strategies include the induction of a specific tolerance to hypothetical disease-relevant antigens and autoantigens. Despite the good results seen in the pilot projects, however, the efficacy of most of these newly developed forms of treatment still need to be confirmed in long-term trials involving adequate numbers of patients.
7964763 Activity and socket wear in the Charnley low-friction arthroplasty. 1994 Aug A clinical study was undertaken to assess the influence of patient-related factors on wear of the socket in Charnley low-friction arthroplasty. One hundred nine arthroplasties in 79 patients were reviewed at an average of 10.3 years. A new method of activity assessment was designed and used to estimate the distance walked by each patient. This method was validated by a pedometer that recorded the time taken by each patient to walk 20 m. Activity level was related to the amount of movement at the level of the prosthetic articulation by calculating the sliding distance of a point at the center of the surface of the head of the femoral component. Wear was found to correlate with patient activity, but not with the physical characteristics of the patient or the time since operation.
1544959 Proximally cemented versus uncemented Freeman-Samuelson knee arthroplasty. A prospective r 1992 Mar We studied the effect of a layer of cement placed under the tibial component of Freeman-Samuelson total knee prostheses with a metal back and an 80 mm intramedullary stem, using roentgen stereophotogrammetry to measure the migration of the tibial component during one year in 13 uncemented and 16 cemented knees. The addition of cement produced a significant reduction in migration at one year, from a mean of 1.5 mm to one of 0.5 mm (p less than 0.01), including a significant reduction in pure subsidence. One year postoperatively the clinical results were similar between the groups, but, at three years, one uncemented knee had required revision.
7788150 Antibodies to the 65 kDa mycobacterial stress protein in west Africans with rheumatoid art 1995 Apr We have studied IgG antibodies to recombinant mycobacterial 65 kDa heat-shock protein in West African rheumatoid arthritis (RA) patients and local control groups, including those with tuberculosis or malaria. Mean levels were higher among the patients with RA than among healthy controls, but did not achieve statistical significance. Our findings may relate to the level of mycobacterial exposure in West Africa.
1424262 Recalcitrant pyoderma gangrenosum--two cases successfully treated with cyclosporin A. 1992 Jan The successful use of cyclosporin A (CSA) in organ transplantation is now well established. In recent years its usefulness has extended to the treatment of cutaneous autoimmune disorders, including pyoderma gangrenosum (P.G.). We report two further cases of recalcitrant P.G., both associated with rheumatoid arthritis (R.A.) which responded to low dose CSA.
7691452 Soluble E-selectin in arthritis. 1993 Oct Cellular adhesion molecules, such as E-selectin, function to recruit leukocytes into inflammatory lesions. Recently, a soluble form of this adhesion molecule, sE-selectin, has been described. In this study we determined soluble E-selectin (sE-selectin) in synovial fluid (SF) and blood samples from patients with rheumatoid arthritis (RA) and other inflammatory disorders and correlated sE-selectin levels with clinical parameters of disease activity. SF, blood, and cells isolated from RA SFs and synovial tissues (STs) were examined from 76 patients. In addition, normal plasma as well as supernatants from cultured human umbilical vein endothelial cells (HUVECs) were obtained. sE-selectin levels were assayed in these fluids and cell supernatants by an enzyme-linked immunoabsorbant (ELISA) assay. SFs from patients with RA had significantly higher sE-selectin levels than did those from osteoarthritis (OA) SFs (P < 0.05). SF sE-selectin levels were correlated with SF leukocyte counts. HUVECs, or RA ST cells enriched in endothelial cells, produced sE-selectin. Neutrophils isolated from RA SFs did not release sE-selectin. SF soluble intercellular adhesion molecule-1 levels correlated positively with sE-selectin levels. We conclude that sE-selectin levels are increased in SFs from RA compared to those from OA. Endothelial cells derived from umbilical vein or from RA STs release sE-selectin. Thus, sE-selectin may be important in the migration of inflammatory leukocytes into diseased RA STs and SFs.
7981997 Leg ulceration in rheumatoid arthritis. 1994 Nov Chronic leg ulcers occur in 1% of the adult population with considerable associated morbidity, and community costs estimated at up to 600 million pounds p.a. in the UK. Leg ulcers appear to be relatively common in patients with RA and are widely believed to be resistant to treatment. Such ulcers are often attributed to vasculitis, but little is known of the occurrence of other potential aetiological factors. This article reviews the epidemiology, natural history and aetiology of chronic leg ulcers in RA as well as the therapeutic options available.
8142964 [A newly developed cementless elbow joint prosthesis]. 1993 Authors describe briefly the history of the development of elbow arthroplasty. They report on their experiences with the silicone, cementless, unconstrained elbow prosthesis developed by them and implanted in 23 cases during 3 years. The prosthesis is described, the operative indication and the problems of the operative technique are reviewed. On the basis of their results and the low number of complications this method of operation is suggested first of all for the successful treatment of elbows with rheumatoid arthritis.
8182639 Binding characteristics of antitype II collagen antibody to the surface of diseased human 1994 Feb OBJECTIVE: Studies have shown that collagen type II (CII) on the intact articular surface of cartilage is partially protected from binding to anti-CII antibodies by material proteinaceous in nature, not present in synovial fluid, synthesized by resident chondrocytes, and exquisitely sensitive to polymorphonuclear (PMN) attack and neutrophil elastase digestion. Thus, anti-CII antibody differential binding to articular cartilage surfaces before and after brief neutrophil elastase digestion may be used as a sensitive marker of cartilage damage. METHODS: We measured binding of anti-CII antibodies to the pannus-free articular surfaces of 4 normal, 11 rheumatoid (RA), and 10 osteoarthritic (OA) cartilage specimens, before and after brief digestion with PMN elastase. In addition, antibody binding was quantitated with an antiserum against a 4 M guanidine extract of human cartilage surface. RESULTS: Whereas anti-CII binding increased 59.0% +/- 2.8 after 1 h incubation of normal cartilage with elastase, both the RA and OA specimens failed to show significant increases (RA: 1.0 +/- 0.1; p < 0.001; OA: 27.2% +/- 1.6, p < 0.05). Moreover, anti-CII antibody binding to untreated cartilage specimens was highest for the RA group (Normal: 189.2.1 +/- 38.7 pg anti-lg/mg tissue; RA: 407.5 +/- 80.6, p < 0.05; OA: 243.6 +/- 50.6, NS). Concomitant binding studies with antiserum against cartilage surface material showed greater antibody binding to the articular surfaces than to the cut cartilage surfaces in normal and OA specimens. RA cartilage samples exhibited somewhat smaller antibody binding to the articular surfaces. CONCLUSION: Our studies suggest that in human inflammatory and noninflammatory arthritides the articular cartilage surface undergoes alterations that can be detected by differential binding with anti-CII antibodies, before and after brief digestion with PMN elastase.
7895391 Factors associated with disease severity in Mexican patients with rheumatoid arthritis. 1994 Nov OBJECTIVE: To investigate clinical, demographic, laboratory, and behavioral variables associated with disease severity in rheumatoid arthritis (RA). METHODS: A case-control study was carried out in a tertiary care center. Participants were RA patients, 16-65 years of age, with a disease duration of > or = 2 years. Selection criteria were established in advance. The sample size was calculated taking into account the prevalence of a low formal education level (< 6 years of school) in a sample of 60 patients. Controls for each case were paired according to age, sex, rheumatoid factor, and disease duration for a case/control ratio of 1:1.8. Cases were defined as those patients having at least two of the following: failure to respond to > or = 3 disease modifying anti-rheumatic drugs, score > or = 3/10 on the Disability Index of the Health Assessment Questionnaire, and disease severity > or = 4/10 as judged by the treating physician on a visual analogue scale. Controls were obtained from the same group but without such characteristics. All of the clinical charts were blindly evaluated for the clinical, demographic, laboratory, and behavioral variables. Descriptive statistics, univariate and multivariate analysis, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: We studied 46 cases and 82 controls. Univariate analysis showed that severity was associated with a low level of formal education (OR 3.15, CI 1.38-7.13), use of non-conventional therapy (OR 2.7, CI 1.34-5.49), treatment with oral steroids (OR 2.6, CI 1.28-6.8), compliance, and disease duration before a confirmed diagnosis of RA. These variables remained in the multivariate model. A low hemoglobin level and an increased platelet count were the biological variables associated with severity. CONCLUSIONS: The evaluation of RA must be conducted in a socio-cultural context since this is in some way linked to disease severity.
8473021 Interaction of the terminal complement components C5b-9 with synovial fibroblasts: binding 1993 Feb The late complement components, apart from their lytic function, are known to trigger the release of various proinflammatory substances from different types of nucleated cells. In the present study, the interaction of C5b-9 with synovial fibroblast cells (SFC) was examined. It was found that incubation of SFC with activated complement components resulted in binding of C5b-9 to the cell membrane; subsequently an increase in abundance of collagenase-specific mRNA was seen, as assessed by Northern blotting. When C8-deficient serum was used as source of complement neither binding of C5b-9 nor an increase in collagenase-specific mRNA could be detected. These findings suggest that C5b-9, which might be generated during rheumatoid inflammation, may contribute to chronic joint destruction by triggering collagenolytic activity.
1283954 Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. 1992 Sep Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non-MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS)
8835295 Antiperinuclear factor: a useful test for the diagnosis of rheumatoid arthritis. 1995 The objective of this study was to determine: (1) the diagnostic value of antiperinuclear factor (APF), (2) the types of immunoglobulins involved in the reaction and (3) the presence of the antibody in paired samples of serum and synovial fluid (SF). We studied 408 serum samples from the following: healthy controls (n = 68), patients with rheumatoid arthritis RA; n = 160, 106 RF-positive and 54 RF-negative and patients with other rheumatic diseases (n = 180). We examined paired serum and SF samples in 27 patients (8 with RA and 19 with other rheumatic conditions). APF was determined by an indirect immunofluorescence assay. A group of 30 APF-positive serum samples was incubated with fluorescent-labelled antisera against IgG, IgM and IgA independently. APF was positive in 55.7% of patients with RF-positive RA, in 35.2% of patients with RF-negative RA, in 11.1% of patients with other rheumatic diseases and in 5.9% of healthy controls. Statistical differences were found between RF-positive RA and the other three groups (P = 0.02, P = 0.0001, P = 0.0001, respectively) and between RF-negative RA and the groups of other rheumatic diseases (P = 0.0001) and healthy controls (P = 0.005). The specificity of the test for RA was 90.2%. APF was present in three SF samples from RA patients (37.5%). The reaction was mediated by immunoglobulins of the IgG class in 100% of those tested, and, in addition, 30% were of IgA and 6.7% of IgM classes. We concluded that APF is a good diagnostic test that could be included in the classification criteria of RA, it can be present in SF and it is predominantly an antibody of the IgG class.