Browse

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

ID PMID Title PublicationDate abstract
9922543 Arthroplasty of the forefoot in rheumatoid arthritis: long-term results after Clayton proc 1998 Dec The present study aims to evaluate long-term results after Clayton resection arthroplasty in patients with symptomatic arthritis of the forefeet. From 1970 to 1995, 109 patients with a total of 184 rheumatoid forefeet underwent Clayton's procedure at an average age of 60 years. Forty-seven of them returned with 82 operated feet for follow-up by means of patient history, physical examination and radiograph an average of 12.8 years later. Overall outcome was judged as successful in 60 of the 82 cases with complete pain relief, remarkably improved gait capacity and use of normal shoes. Sixteen of the feet were definitely improved, but slight to moderate pain, inadequate balance and contact with the ground, limited walking distance and use of large shoes were signs of decreased operation success. The remaining 5 feet showed recurrent splay-foot deformity with intolerable pain, functional disability and restricted gait capacity even though specially made surgical shoes were used. The Clayton procedure appears to be a suitable method for surgical correction of symptomatic rheumatoid forefeet.
9120317 Critical residues on HLA-DRB1*0402 HV3 peptide for HLA-DQ8-restricted immunogenicity: impl 1997 Apr 1 Recently, we have proposed that the combination of HLA-DQ and -DR alleles is responsible for the association of the HLA class II region with rheumatoid arthritis (RA). According to this model, some HLA-DQ alleles, namely DQ4, DQ7, DQ8, and DQ9, predispose carriers to severe RA, but a self peptide of sequence KDILEDERAAVDTYC from the third hypervariable (HV3) region of some DRB1 alleles, including DRB1*0402, can protect from the disease if presented by DQ molecules. This model implies that DQ4, DQ7, DQ8, and DQ9 should be able to present a set of common peptides, despite polymorphisms in their Ag binding groove. In the present study, we have further analyzed the immunogenicity of the DRB1*0402 HV3 peptide in DQ8-transgenic mice. We found that the motif DERAA guarantees DQ8-restricted immunogenicity, and that R is the main anchor residue for binding of the DRB1*0402 peptide to DQ. Interestingly, the p1 pocket that probably controls binding of the R residue is identical in all four RA-associated DQ molecules. Our results imply that the association of RA with some DR subtypes can be explained by their linkage with DQ alleles displaying a binding site for similar "arthritogenic" peptides.
10229141 Antifilaggrin antibodies in recent-onset arthritis. 1999 We evaluated the sensitivity and prognostic value of an enzyme-linked immunosorbent assay (ELISA) for the measurement of antifilaggrin antibodies (AFA), using filaggrin purified from human skin as an antigen. The AFA test was applied to a series of 306 patients with various recent-onset inflammatory joint diseases. The results were compared to those of the conventional immunofluorescence tests for antikeratin antibody (AKA) and antiperinuclear factor (APF) and of the rheumatoid factor (RF) tests from a previous study. There was a very good agreement between the results of the tests for APF and AFA (kappa-value 0.79 in patients with peripheral poly/oligoarthritis). The agreement between the tests for AKA and AFA was significant but less pronounced (kappa-value 0.50). The AFA test detected 10/22 of the RF-negative erosive cases, particularly those with a large number of erosive joints. Thus, the test for AFA supplements RF in the prediction of erosiveness.
10618069 Identification of Mycoplasma fermentans in synovial fluid samples from arthritis patients 2000 Jan Since 1970 Mycoplasma fermentans has been suspected of being associated with rheumatoid arthritis. However, this association has been difficult to prove, and this has been our goal. The distribution of M. fermentans was studied in the synovial fluid of patients suffering from different arthritides. Samples of synovial fluid were taken from patients with well-defined disease and a clear diagnosis. After removal of the inflammatory cells and hyaluran, they were treated with proteinase K and tested by a single or fully nested PCR with primers directed against part of the two 16S rRNA genes of M. fermentans. The product was sequenced automatically, by using an ALF Express automatic sequencer, to confirm the mycoplasma species and to identify the strain since the two genes were usually found to be polymorphic. This was also true of the type strain, strain PG18. M. fermentans was detected in 23 of 26 (88%) rheumatoid arthritis patients, and four different strains were found. It was also found in 7 of 8 (88%) of the nonrheumatoid inflammatory arthritis patient group, which consisted of one patient with reactive arthritis, one patient with pauciarticular juvenile chronic arthritis, two patients with gout, two patients with ankylosing spondylitis, and two patients with psoriatic arthritis, only one of whom was infected with M. fermentans. It was not detected in any of the 10 osteoarthritis patients. M. fermentans was therefore found to be a variable and very common organism in arthritic patients with inflammatory joint exudates and may well prove to be important in the etiology of the diseases.
10834861 Interindividual and intra-articular variation of proinflammatory cytokines in patients wit 2000 Jun OBJECTIVES: Assessment of the numbers and spatial distribution of cells producing interleukin 1alpha (IL1alpha), interleukin 1beta (IL1beta), tumour necrosis factor alpha (TNFalpha), and interleukin 6 (IL6) in the synovial membranes of patients with rheumatoid arthritis (RA). METHODS: Synovial tissue specimens from 40 patients with RA and eight patients with non-rheumatic disease were obtained by arthroscopy guided biopsy techniques or during joint surgery. A modified immunohistochemical method detecting cytokine producing rather than cytokine binding cells was applied to determine cytokine synthesis in fixed cryopreserved sections. Computerised image analysis methods provided comparative quantitative assessments. RESULTS: A wide variation between subjects was recorded for both quantities and profiles of expressed cytokines, despite similar macroscopic and histopathological features of inflammation. IL1alpha and IL1beta were the most abundant monokines identified, though produced at different sites. IL1alpha was predominantly seen in vascular endothelial cells, whereas IL1beta staining was mainly shown in macrophages and fibroblasts. Concordant results for the detection of TNFalpha at protein and mRNA levels were obtained with an unexpectedly low number of TNFalpha producing cells compared with IL1 expressing cells in many patients with RA. Specimens acquired arthroscopically from areas with maximum signs of macroscopic inflammation showed an increased number of TNFalpha producing cells in pannus tissue compared with that occurring in synovial villi of a given joint. This clustered distribution was not found for cells expressing any of the other studied cytokines. CONCLUSION: The recorded heterogeneous profile of proinflammatory cytokine synthesis in the synovial membrane among patients with RA may provide a clue for an understanding of the wide variation in responsiveness to different modes of antirheumatic treatment between patients.
10328574 Hematopoietic stem cell transplantation in rheumatic diseases. 1999 May The concept of using hematopoietic stem cell transplantation to treat patients with autoimmune disease was first provided by animal studies and anecdotal case reports. Advances over recent years in autologous hematopoietic stem cell transplantation, most notably cytokine-mobilized peripheral blood stem cells, have been followed by its specific use to treat severe autoimmune and inflammatory diseases. Guidelines have been published, and, by March 1999, 150 cases were registered with the International Autoimmune Disease Stem Cell Project Database. This review summarizes the literature published with respect to inflammatory rheumatic disease over the past few years and discusses future directions aimed at refining this intensive approach.
10422543 COX-2: separating myth from reality. 1999 Several currently available nonsteroidal anti-inflammatory drugs (NSAIDs) have been evaluated for their relative selectivity in inhibiting the two cyclooxygenase (COX) isozymes, COX-1 and COX-2. Arguments have been made that more selective inhibitors of COX-2 will be safer than less selective ones. Rankings of the COX-2/COX-1 inhibition ratios of various NSAIDs as they relate to the agents' toxicities have been used as evidence that COX-2 selectivity is an important factor in the upper gastrointestinal (GI) safety of some NSAIDs. Unfortunately, none of these claims has been supported by endoscopy studies in treated patients. Since all NSAIDs inhibit COX-1, they all cause upper GI mucosal damage. What is needed are specific COX-2 inhibitors that do not inhibit COX-1. Such agents are currently under development. Ongoing clinical trials will determine the potential role for specific COX-2 inhibitors in the treatment of arthritis and pain. If specific COX-2 inhibitors are shown to be both safe and effective, the treatment of rheumatic diseases will be revolutionized.
10606373 Prevalence of rheumatoid arthritis and spondyloarthropathy in Brittany, France. Société 1999 Dec OBJECTIVE: To document the prevalence of rheumatoid arthritis (RA) and spondyloarthropathy (SpA) in Brittany, France. METHODS: (1) Members of rheumatism self-help groups screened cases using questionnaires. (2) Rheumatologists in our unit contacted persons who had possible inflammatory rheumatic diseases and persons who refused the first interview. (3) When diagnosis remained unknown or discordant with the questionnaire, the general practitioner or the rheumatologist of these patients was interviewed. (4) Patients without diagnosis and who had not had a rheumatological examination were examined without charge by a rheumatologist. RESULTS: An overall prevalence rate of 0.62% (0.33-0.91) and 0.47% (0.22-0.72) was found for RA and for SpA, respectively. The prevalence of RA and SpA was 0.86 (0.39-1.33) and 0.53 (0.16-0.9) in women and 0.32 (0.01-0.63) and 0.41 (0.05-0.77) in men. The minimum prevalence of RA and SpA calculated on the estimated initial group (3189 persons) was 0.53 (0.28-0.78) and 0.41 (0.18-0.63), respectively. CONCLUSION: Our telephone survey revealed that the prevalences of RA and SpA are nearly similar among our population and that SpA is as common in women as in men.
9433400 The prevalence and severity of rheumatoid arthritis in Oslo. Results from a county registe 1997 The objective was (1) to examine the prevalence of rheumatoid arthritis (RA) by a county patient register, (2) to cross-validate the register findings by a postal population survey, and (3) to estimate prevalences of disease subsets according to age, sex, and levels of physical disability. The study was performed within a county setting in the city of Oslo with 356,486 inhabitants between 20 and 79 years of age. Prevalence estimates were calculated from a county patient register comprising 1333 patients with RA and a population survey of 10,000 inhabitants. The overall prevalence of RA between 20 and 79 years was 0.437 (95% CI 0.413, 0.461) after adjusting for the incompleteness of the register by a factor of 1.17. Prevalences exceeding 1.0% was only found among females over 60 years. The prevalence of RA with MHAQ scores > or = 1.5 and > or = 2.0 (range 1-4) was 0.225 (95% CI 0.209, 0.243) and 0.099 (0.088, 0.111) respectively. We conclude that RA is less frequent in the city of Oslo than stated in most of the literature. The prevalence of RA with physical disability levels assumed to be associated with increased mortality is less than half of the overall prevalence of 0.4-0.5%.
11147850 Symptomatic C1-2 fusion failure due to a fracture of the lateral C-1 posterior arch in a p 2001 Jan The authors report a case in which the lateral C-1 arch fractured in a patient with rheumatoid arthritis and an intact fusion mass; this patient had previously undergone a C1-2 Brooks-type fusion. This unique complication occurred secondary to continued resorption of the C1-2 rheumatoid pannus. Two years after occipitocervical fusion the patient has made a complete neurological recovery.
9440148 Binucleated and multinucleated forms of plasma cells in synovia from patients with rheumat 1997 A morphological examination of synovial tissue from 25 patients with rheumatoid arthritis revealed that binucleated or multinucleated plasma cells were present in all samples and absent in synovia obtained from 16 control patients. Plasma cells containing two, three of four nuclei constitute a mean 3% of the total plasma cell population. They were always found amongst plasma cell infiltrates and in close association with small blood vessels. Ultrastructural analysis found no evidence of cellular membranes separating the individual nuclei in binucleated or multinucleated plasma cells, suggesting that the cells did not arise from fusion. Some of these plasma cells had a diameter approaching 100 microns, and many were in intimate contact with macrophages. The demonstration of a few cells with mitotic figures within the infiltrates suggests that the maintenance of plasma cell numbers in rheumatoid synovium may depend, in part, upon their local proliferation.
11678909 Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells. 2001 Oct Membrane-type 1 matrix metalloproteinase (MT1-MMP) is thought to be a putative regulator of pro-gelatinase A (MMP-2) in the rheumatoid synovium. In this study, we examined the effects of IL-1beta, one of the inflammatory cytokines, on the expression of MT1-MMP and the activation of pro-MMP-2 using rheumatoid synovial cells. We also studied the effects of KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), a new disease-modifying anti-rheumatic drug (DMARD), on MT1-MMP expression of rheumatoid synovial cells. Type B synovial cells (fibroblast-like synovial cells) were cultured with KE-298 (25-100 microg/ml) in the presence of IL-1beta for 48 h. Activation of pro-MMP-2 secreted from synovial cells was analysed by gelatin zymography. Reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect MT1-MMP mRNA. MT1-MMP protein expression on synovial cells was examined by anti-MT1-MMP immunoblot. An active form of MMP-2 was demonstrated in the culture media conditioned by IL-1beta-stimulated synovial cells. In addition, MT1-MMP mRNA and protein expression of rheumatoid synovial cells were increased by IL-1beta treatment. KE-298 blocked this IL-1beta-induced pro-MMP-2 activation and MT1-MMP expression, but did not affect IL-1beta-induced tissue inhibitor of metalloproteinase-2 (TIMP-2) secretion from rheumatoid synovial cells. These findings indicate that activation of rheumatoid synovial cells by IL-1beta results in the induction of MT1-MMP expression. Given that MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a novel mechanism whereby cytokine may contribute to articular destruction in rheumatoid arthritis (RA). KE-298 may prevent this process by down-regulating MT1-MMP expression.
10986304 Patient-initiated hospital follow-up for rheumatoid arthritis. 2000 Sep OBJECTIVES: To evaluate the clinical efficacy, cost and acceptability of a shared care system of patient- or general practitioner (GP)-initiated hospital review in rheumatoid arthritis (RA). METHODS: A 2-yr randomized controlled trial of routine rheumatologist-initiated review was compared with a shared care system. Shared care patients had no routine follow-up but patients or GPs initiated access to rapid review by the multidisciplinary team via a nurse-run helpline. Control patients had a rheumatologist-initiated medical review at intervals of 3-6 months. Clinical and psychological status, resource use, and patient and GP satisfaction and confidence were assessed. Three-monthly clinical data were assessed (blind) for safety monitoring, with failure set at a 20% increase in pain, disability or disease activity. RESULTS: Two hundred and nine established RA patients participated, of whom 182 were evaluable. Safety-net failures were not different between groups. Shared care patients had less pain (24 months, 3.9 cm on a 10-cm visual analogue scale vs 4.8 cm for controls; P: < 0.05), a smaller increase in pain over 2 yr (+ 0.4 cm vs +1.6 cm for controls; P: < 0.01), greater self-efficacy (6, 15, 18, 21 months, P: < 0.05), used 33.5% less resources (208 ponds sterling per patient per year vs 313 pound sterling for controls; P: < 0.001) and were more confident in the system (6, 9, 12, 18, 21, 24 months, P: < 0.01 to P: < 0.001). CONCLUSIONS: A patient-initiated system for hospital review over 2 yr offers some clinical benefit compared with the traditional system, using fewer resources and attracting greater patient confidence. Longer-term assessment of the system would be appropriate.
10989515 Therapeutic and physical fitness exercise prescription for older adults with joint disease 2000 Aug Aging with joint disease does necessarily result in chronic pain, adoption of a sedentary lifestyle, and functional dependency. Several randomized controlled trials clearly show that regular exercise does not exacerbate pain or accelerate disease progression. On the contrary, these studies suggest that exercise training may increase the physiologic reserve and reduce the risk for functional dependency in older adults with joint disease. The goals for an exercise program should be directed toward increasing flexibility, muscle strength, endurance, and cardiovascular fitness. An exercise training program that is tailored specifically to an older adult's physical limitations may achieve these goals, and by optimizing patient safety lead to improve long-term exercise compliance.
9313389 A comparison of patients with late-stage rheumatoid arthritis and osteoarthritis of the sh 1997 Feb OBJECTIVE: To compare the function and health status of individuals with advanced rheumatoid arthritis (RA) and osteoarthritis (OA) of the shoulder using standardized patient self-assessment tools. METHODS: A group of patients with late-stage arthritic involvement of the shoulder was evaluated at the time of initial presentation using 2 questionnaires, one focusing on shoulder function and other on overall health status. RESULTS: There was substantial variability in the shoulder function and health status within each diagnostic group; however, both groups demonstrated significant deficits in their Simple Shoulder Test responses and in many of their Health Status Questionnaire-Short Form 36 scores. While the patients with RA tended to have somewhat greater impairment of shoulder function, many of the differences were not statistically significant. By contrast, most health status parameters were significantly more impaired in the patients with RA. CONCLUSIONS: Among patients with late-stage shoulder arthritis, the overall health status of those with RA is significantly worse than those with OA. Differences in health status may be important in selecting the optimal management for individual patients with late-stage shoulder arthritis. Self-assessment questionnaires are effective in characterizing these differences.
10086214 Connective tissue disease and silicosis. 1999 Apr BACKGROUND: To determine the prevalence of connective tissue disease in a cohort of individuals with silicosis, we reviewed the medical records and questionnaires from individuals reported from 1987 to 1995 to a state surveillance system for silicosis. Reporting of individuals with silicosis is required by state law. Cases were reported by hospitals, physicians, the state workers' compensation bureau, or from death certificates. Only individuals who met the criteria for silicosis developed by the National Institute for Occupational Safety and Health (NIOSH) were included in the analysis. RESULTS: A questionnaire was completed for all 583 cases. Medical records were available for 463. There were 24 people with rheumatoid arthritis, one with scleroderma, and one with systemic lupus erythematosus. All were men. The prevalence of rheumatoid arthritis was 5.2% (relative risk (RR) 2.73, 95% confidence limit (CL) 1.75-4.06). The prevalence of scleroderma was 0.2% (RR 15.65, 95% CL 0.21-87.03) and the prevalence of systemic lupus erythematosus was 0.2% (RR 11.37, 95% CL 0.15-63.23). This is an approximately 2.5-15-fold increased risk for these connective tissue diseases compared to estimated prevalences in the general population. Individuals with silicosis and connective tissue disease did not differ from individuals with silicosis but without connective tissue disease by race, age, type of industry where exposed to silica, history of tuberculosis, whether or not they had applied for workers' compensation, and whether or not they had progressive massive fibrosis on chest x-ray. CONCLUSION: Although the association between scleroderma and silicosis has been more widely reported in the literature, the prevalence of rheumatoid arthritis was greater than the prevalence of scleroderma or systemic lupus erythematosus among a cohort of individuals with silicosis.
10986298 Infrequency of detection of particle-associated MSRV/HERV-W RNA in the synovial fluid of p 2000 Sep OBJECTIVES: To determine whether the recently identified multiple sclerosis-associated retrovirus, MSRV, is detectable in the serum and synovial fluid of patients with rheumatoid arthritis (RA). METHODS: A reverse transcription-polymerase chain reaction (RT-PCR) assay was used to seek evidence of particle-associated MSRV/HERV-W RNA in the plasma and synovial fluid of patients with RA and controls. Stringent precautions were taken to avoid detection of contaminating human genomic DNA and cellular RNA sequences. RESULTS: Thirty-seven plasma samples were tested (20 from RA patients and 17 from controls) but none had detectable MSRV/HERV-W RNA. Synovial fluid samples were available from nine patients with RA and 10 controls. Particle-associated MSRV/HERV-W RNA was reproducibly detected in two of nine synovial fluid samples from RA patients and in one control sample. The identity of RT-PCR products was confirmed by sequencing. CONCLUSION: MSRV/HERV-W RNA sequences are detectable in the synovial fluid of a small proportion of RA patients, but this phenomenon may not be specific to RA.
11771529 Eosinophilia as a side-effect of methotrexate in patients with chronic arthritis. 2001 This report describes isolated reversible eosinophilia without additional subjective symptoms or signs in three patients on methotrexate therapy, two of them with juvenile idiopathic arthritis and one with rheumatoid arthritis.
9502411 Focally regulated endothelial proliferation and cell death in human synovium. 1998 Mar Angiogenesis and vascular insufficiency each may support the chronic synovial inflammation of rheumatoid arthritis. We have shown by quantitative immunohistochemistry and terminal uridyl deoxynucleotide nick end labeling that endothelial proliferation and cell death indices were each increased in synovia from patients with rheumatoid arthritis compared with osteoarthritic and noninflamed controls, whereas endothelial fractional areas did not differ significantly among disease groups. Markers of proliferation were associated with foci immunoreactive for vascular endothelial growth factor and integrin alpha(v)beta3, whereas cell death was observed in foci in which immunoreactivities for these factors were weak or absent. No association was found with thrombospondin immunoreactivity. The balance between angiogenesis and vascular regression in rheumatoid synovitis may be determined by the focal expression of angiogenic and endothelial survival factors. Increased endothelial cell turnover may contribute to microvascular dysfunction and thereby facilitate persistent synovitis.
9428733 Highly increased levels of active stromelysin in rheumatoid synovial fluid determined by a 1997 Dec 1 Stromelysin-1 (MMP-3) is an important member of the matrix metalloproteinase family. In joint-degrading diseases like arthritis, elevated levels of MMP-3 protein are detected in synovial fluid using immunological methods. However, these methods do not discriminate between active and inactive enzyme. In the present study, a specific stromelysin activity assay was developed using the selective fluorogenic substrate TNO003 (Dabcyl-Gaba-Arg-Pro-Lys-Pro-Val-Glu / Nva-Trp-Arg-Glu-(EDANS)-Ala-Lys-NH2, / =cleavage site). For its use in biological media, cleavage of TNO003 by enzymes other than stromelysin was effectively blocked by a proteinase inhibitor cocktail. Spiking of MMP-3 to synovial fluid resulted in an MMP-3 concentration-dependent linear increase in activity. The measured MMP-3 activity was not affected by the addition of MMP-13, even in a 5-fold excess over MMP-3. Synovial fluid from rheumatoid arthritis patients demonstrated 100-fold higher levels of active stromelysin than control synovial fluids.