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

ID PMID Title PublicationDate abstract
8340199 Social process and the assessment of a new imaging technique. 1993 Summer Each group involved in the development of a new medical technology constantly assesses the value of the emergent technique in terms of the group's own specific goals and conventions. The history of infrared thermography demonstrates the social nature of this assessment process.
8536371 High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expressi 1995 Dec The CD30 is a surface molecule expressed by Th2-type lymphokine-producing T cells upon activation. CD30-expressing activated T cells release a soluble form of the molecule, which can be detectable both in vitro and in vivo. In the present study, high levels of soluble CD30 were found in peripheral blood and synovial fluid from patients with RA. However, CD30+ CD3+ cells, either CD4+ or CD8+, were significantly present in synovial fluid, but not in peripheral blood, of RA patients. Serum values of soluble CD30 were higher in active than inactive RA patients and directly correlated with rheumatoid factor serum titres. These data strongly support an involvement of CD30+ T cells in the immune processes of rheumatoid synovitis, and may suggest a relationship between Th2-type cytokine-secreting T cells and the pathological response in RA.
7674231 Cyclosporin A increases somatomedin C insulin-like growth factor I levels in chronic rheum 1995 Jun OBJECTIVE: To determine whether anabolic hormones that affect the musculoskeletal system and active on the immune cells changed during cyclosporin A (CysA) therapy. METHODS: We carried out a randomized study of patients with rheumatic disease attending the outpatient clinic for rheumatic diseases. Twenty-four patients with chronic arthritis [20 with rheumatoid arthritis (RA) and 4 with psoriatic arthritis (PsA)] were divided into 2 groups (10 RA, 2 PsA) and randomly given CysA 5 mg/kg daily or hydroxychloroquine (OH-Chlor) 6 mg/kg daily in divided doses. RESULTS: A significant increase of insulin-like growth factor I (IGF-I) (somatomedin C) levels and of bone Gla protein was shown after 2 months in the CysA treated group, but not in the OH-Chlor group. A statistically significant correlation was observed between changes of IGF-I levels and of dehydroepiandrosterone sulphate (DHEAS). This finding was confirmed in a further series of 39 patients. No changes were seen in 25 OH-D, 1-25(OH)2-D3 or parathyroid hormone after CysA. CONCLUSION: The effects of CysA on IGF-I may explain some of the clinical, immunologic, and metabolic results during CysA treatment of rheumatic diseases.
7738950 Fibromyalgia versus rheumatoid arthritis: a longitudinal comparison of the quality of life 1995 Feb OBJECTIVE: To evaluate and compare the quality of life of patients with fibromyalgia (FM) and rheumatoid arthritis (RA). METHODS: Forty-four women with FM and 41 with RA were studied. There were 3 evaluations, with a 3-month interval. Besides special and general clinical examinations, the following tests were applied: pain numerical scale (PNS), Health Assessment Questionnaire (HAQ), Fibromyalgia Impact Questionnaire (FIQ), Arthritis Helplessness Index (AHI), Modified Post-Sleep Inventory (PSI), and questions about sleep disorders and socioeconomic impact. RESULTS: Results include the following: tender points (TP): FM = 13.9, RA = 2.9; PNS: FM = 7.2, RA = 6.8; HAQ: FM = 0.90, RA = 1.22; FIQ: FM = 47.2, RA = 42.5; AHI: FM = 32.7, RA = 31.8; sleep quality--mean duration of daily sleep: FM = 6.7 h, RA = 6.1; PSI scores: FM = 64.6, RA = 57.2. On questioning regarding economic impact, there was a decrease in family income for 65% of patients with FM and 75.1% for those with RA. Fifty-five percent of patients with FM and 66.6% of those with RA received social security aid. At followup evaluation, there was a statistically significant improvement in the following items for the patients with FM: TP count, HAQ, and AHI. The patients with RA improved in number of TP and AHI. CONCLUSION: FM has a negative impact on quality of life, similar to RA. Clinical, functional, and economic problems related to the disease were observed. The alteration observed remained relatively stable during the study period, except for physical disability.
8348277 Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the i 1993 Aug In a randomized double-blinded placebo-controlled trial, 41 patients with RA starting on i.m. sodium aurothiomalate (SAT) therapy were randomized to receive three doses of either 500 mg methylprednisolone (MP) orally and a placebo injection or 120 mg of i.m. depot methylprednisolone acetate (MPA) and oral placebo tablets at 4-weekly intervals. Disease activity was assessed by visual analogue scale (VAS) of pain, grip strength (GS), tender joint count (JC), and Health Assessment Questionnaire (HAQ). Laboratory assessment was by haemoglobin concentration (Hb) and ESR. A composite index of Disease Activity score (IDA) was constructed using all six measurements. The group receiving i.m. MPA showed greater improvement when compared with the group receiving oral MPA. These changes were statistically significant (P < 0.05) for ESR (weeks 2, 6, 8, 10, 12), VAS (week 4, 6, 8), JC (weeks 2, 4, 6, 8, 10) and HAQ (weeks 2, 8, 10). Statistically significantly (P < 0.05) greater improvement in Hb was seen throughout all time points in favour of the group treated with i.m. MPA. Using the IDA score to summarize the results, patients treated with i.m. MPA had better disease remission from weeks 2-12. In all measures, except Hb, no statistically significant difference between the two groups was seen by 16 weeks. We conclude that 120 mg i.m. depot MPA is more effective at inducing improvement in disease activity than 500 mg of oral MPA in RA patients starting on SAT therapy.
7856731 Role of interleukin 1 in antigen-induced exacerbations of murine arthritis. 1995 Jan The mechanism underlying the chronic and intermittent course of rheumatoid arthritis is not elucidated. In the present study, the role of interleukin 1 (IL-1) was investigated in exacerbations of antigen-induced arthritis in mice. A flare-up of smoldering inflammation (weeks 3 to 4 of antigen-induced arthritis) was inducible by injection of a small amount of methylated bovine serum albumin into the hypersensitive knee joint. Immunohistochemistry showed IL-1 expression in the synovial lining layer and in focal areas of the inflamed synovium during the flare-up. IL-1 was also measured in 1-hour culture supernatant of synovial tissue taken during the flare-up by a bioassay. The expression of both immunoreactive and bioactive IL-1 in the hypersensitive joint peaked around 6 hours after antigen (2 micrograms of methylated bovine serum albumin) injection and declined thereafter. Antigen rechallenge induced an acute joint swelling of the arthritic joint but not in the naive joint of the sensitized mouse, yet synovia of both joints produced IL-1 after antigen injection. Remarkably, a single intravenous injection of rabbit anti-IL-1 alpha and -beta antibodies 1 hour before antigen rechallenge neutralized IL-1 in the joint. Anti-IL-1 treatment significantly reduced the antigen-induced joint swelling (30 to 40%) but did not affect the profound influx of polymorphonuclear cells in the onset of the exacerbation. However, a profound relief of the inflammation (synovitis) was obtained by IL-1 blockade on day 4 of the exacerbation. Chondrocyte proteoglycan synthesis was markedly suppressed in the antigen-challenged naive knee joints suggesting that this was a direct IL-1 effect as the inflammation was insignificant. Anti-IL-1 treatment was able to maintain chondrocyte proteoglycan synthesis in the antigen-rechallenged joint, which was highly suppressed in the control group. Furthermore, the enhanced proteoglycan breakdown in the antigen-rechallenged joints was significantly decreased in the anti-IL-1 group. We concluded that IL-1 is an important mediator in exacerbations of murine arthritis, and amelioration of cartilage pathology was obtained with anti-IL-1 antibody treatment.
1384516 Selection of T cell receptor V beta elements by HLA-DR determinants predisposing to rheuma 1992 Sep OBJECTIVE: Rheumatoid arthritis (RA) is genetically linked to a sequence motif encoding for the middle portion of the alpha-helical loop, which is adjacent to the antigen-binding groove of the HLA-DR molecule. The disease-associated element might be involved in binding the antigen or in interacting with the T cell receptor (TCR). To investigate the contribution of the disease-associated element in T cell recognition events, we studied structural requirements in the interaction of T cell clones with HLA-DR determinants. METHODS: T cell clones restricted to disease-associated HLA-DR determinants were established by allogeneic stimulation of HLA-DRB1*0401+ or *0401- responders with HLA-DRB1*0404/8+ stimulators. Allele specific primer sets were used to identify the V beta gene segment expressed by individual clones. Sequence analysis was applied to study the diversity of the TCR beta-chain junctional regions. RESULTS: The repertoire of TCR V beta elements was strongly biased toward the usage of V beta 6. HLA-DRB1*0401+ and *0401- donors preferentially recruited V beta 6+ T cells to recognize the disease-associated HLA-DR determinant. Sequence data revealed that the V beta 6.6/7 and V beta 6.8/9 subtypes of the V beta 6 multigene family were overrepresented. The TCR beta chains were characterized by a high degree of junctional diversity, supporting the view that a multitude of peptide-DR complexes were recognized and that the preferential use of V beta 6 was dictated by the TCR beta chain-DR beta 1 chain contact. CONCLUSION: T cells reactive with the disease-associated HLA-DR structure are nonrandomly selected. The HLA-DR component predisposing to RA might define molecular requirements that restrict the TCR-HLA interaction. Thus, the phenomenon of HLA association in RA might reflect a genetic control of T cell recognition, through the selection of the TCR repertoire.
7679058 Reduction of monocyte-macrophage activation markers upon anti-CD4 treatment. Decreased lev 1993 Feb Anti-CD4 MoAbs have been successfully used in initial treatment trials of rheumatoid arthritis. One remarkable feature of this therapy was the early reduction of synovitis along with a decrease of the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). Since not only T helper cells, but also monocytes-macrophages bear the CD4 antigen, the question was raised whether the immediate effects observed may have been in part due to an influence on the mononuclear phagocyte system. Immediately after MoAb infusions, a significant reduction of the absolute peripheral blood monocyte count down to 30% (P < 0.001) was noted within the first hour of injection. In contrast to strikingly elevated levels of soluble CD4 after treatment which was indicative of T cell lysis, soluble CD14 levels did not rise, but rather decreased from previously elevated levels. Before treatment, activation of the monocyte-macrophage system had been signified by elevated serum levels of IL-1, IL-6, CRP and neopterin as well as a marked in vitro production of IL-1, tumour necrosis factor-alpha (TNF-alpha) and IL-6. Subsequent anti-CD4 treatment resulted in a rapid and significant reduction of monocyte-derived circulating cytokines and mediators concordant with a reduced capacity to produce IL-1, TNF-alpha, and IL-6 in those patients who demonstrated clinical benefits. Therefore, studies of monocyte activation markers may be useful in identifying subsequent responders to anti-CD4 therapy.
7725071 The distribution and abnormal morphology of plasma cells in rheumatoid synovium. 1995 May This study assessed the distribution and structural features of plasma cells in rheumatoid synovial tissue. Plasma cells were found to be the predominant infiltrating mononuclear cells (mean 40%) in relation to lymphocytes and monocytes, and there was a direct relationship between their number in the infiltrates and the total number of mononuclear leucocytes (P = 0.007). Plasma cells were also seen in intimate contact with macrophages intermixed with synovial lining cells, and closely associated with small blood vessels. They often surrounded these blood vessels and sometimes were seen lying within the vessel walls themselves. Ultrastructural analysis revealed that many synovial plasma cells were considerably larger than plasma cells of a normal size and possessed a marked distension of the cisternae of rough endoplasmic reticulum. Furthermore, plasma cells in close proximity to blood vessels often appeared to be undergoing migration. These observations imply that in rheumatoid synovium, plasma cells are metabolically very active and occupy a pivotal position for the secretion of antibodies into both the vascular and the extravascular compartments.
7835008 Additive two DMARD therapy of the patients with rheumatoid arthritis. 1994 Sep From the beginning of 1987 to the end of 1989, 72 rheumatoid arthritis patients (RA) whose disease could not be controlled by a single disease modifying antirheumatic drug (DMARD) were selected for the trial treatment. They continued the DMARD treatment used initially at its regular dose, and then started another DMARD regimen at 1/3 to 1/2 of the regular dose as an additive DMARD treatment, which we have designated as Additive Two DMARD Therapy (ATDT). The patients were followed until the end of 1992. In the 3 months of ATDT, the effectiveness of ATDT was obtained in 42 (58.3%) patients who showed more than a 30% decrease in the initial Lansbury's activity index (AI). The rate of side effects at 3 months were 5.6%. Tiopronin, bucillamine or salazopirine added to gold sodium thiomalate or tiopronin were suggested as the recommended DMARD combinations for ATDT. The suppressive effects on AI, ESR, CRP and rheumatoid factor continued for as long as 18 to 24 months. The mean period of ATDT was 21.7 months and that at which ATDT proved useful was 31.9 months. A discontinuation of the first DMARD treatment without any following disease aggravation was obtained in 10 of 15 patients whose disease activity had been sufficiently suppressed for longer than a year. In conclusion, ATDT was suggested to be a useful way of treating RA patients whose disease activity could not be controlled by a single DMARD treatment, as well as a way of evaluating the next DMARD while the ongoing DMARD was observed to gradually lose its initial drug effect.
7688238 [Tenosynovectomy of the flexors in rheumatoid polyarthritis. Analytic study of short term 1993 Between 1970 and 1988, 115 patients with rheumatoid arthritis underwent flexor tenosynovectomy. Fifty patients were reviewed (64 hands). The diagnosis of flexor tenosynovitis remains a clinical diagnosis. Three main groups can be distinguished: isolated carpal tenosynovitis (20%), palmodigital tenosynovitis (50%), diffuse tenosynovitis (30%). Standard surgical techniques were used, particularly in terms of the incisions. All patients underwent rehabilitation in the same rehabilitation centre. The authors analyse their results by comparing overall preoperative and postoperative mobility of the fingers (TAM: Total Active Motion, TPM: Total Passive Motion) and the angular gain in each joint (MCP, PIP, DIP). They report the results obtained at 4 months to eliminate the bias related to progression of the disease. The long-term results (8 years of follow-up) are also analysed. Statistical analysis compares two groups depending on whether flexor tenosynovectomy was isolated (44%) or combined with a dorsal surgical procedure at the same operation (extensor synovectomy, articular synovectomy, stabilisation-realignment of the dorsal aspect of the wrist, resection of the ulnar head) (56%). Ninety percent of patients declared themselves to be subjectively improved. Objectively, mobility was always improved at 4 months then deteriorated to return to its preoperative level at 8 years. Only three patients were reoperated for recurrence. Flexor tenosynovectomy in rheumatoid arthritis is an excellent operation. Its analgesic effect is maintained in time and, when performed early, it appears to protect the patient from the risk of subsequent tendon rupture.
7837168 Rheumatoid nodulosis of the meninges. 1994 Oct Rheumatoid nodulosis of the brain and leptomeninges has been reported only rarely, usually in patients with severe rheumatoid arthritis (RA). We describe the occurrence of leptomeningeal rheumatoid nodulosis occurring in a patient with nondeforming RA occurring in the setting of methotrexate therapy.
8179229 Preliminary study of the tryptase levels in the synovial fluid of patients with inflammato 1994 May This study examined levels of tryptase, a specific mast cell product, in synovial fluid. Samples of synovial fluid from eight patients with rheumatoid arthritis and ten with other arthritides were measured in solid-phase immunoradiometric assays. Elevated concentrations of tryptase were present in samples from three patients with rheumatoid arthritis, one with psoriasis, and one with Reiter's syndrome. The data support the theory that mast cell activation is involved in the pathogenesis in some inflammatory joint diseases, but activation does not appear to be disease specific.
8827863 The radiology of early arthritis. 1996 Jul Accurate diagnosis of early arthritis is important because successful treatment with preservation of joint structure and function is most likely when specific therapeutic interventions are instituted early in the disease. Early arthritis may be difficult to accurately diagnose clinically, even for experience practitioners. High-yield radiologic studies are possible, but the radiologist must realize that for each patient and each disease, how and where to look, and what to look for, may differ. Conventional radiographs remain the most important screening studies for both the axial and appendicular skeleton. Other modalities, especially MRI, have limitations but can be powerful tools in problem cases. Each disease has target areas of early involvement that may differ from the classic distribution seen once the process is established. A careful examination of these areas for subtle but characteristic early findings will often be rewarding.
1306077 Small airway disease in rheumatoid arthritis. 1992 Jul Variety of pulmonary lesions are thought to be associated with rheumatoid arthritis (RA). These lesions traditionally have included pleurisy with or without effusion, Caplan's syndrome, pulmonary rheumatoid nodules, diffuse interstitial fibrosis, and pulmonary arteritis and hypertension. But little attention has been paid to the airways in RA. Recently, several reports have suggested an association between airflow limitation and RA, but its incidence is not known. Also whether there exists a parameter of disease activity of RA, suggesting the presence of small airway disease (SAD) is not clear. To answer these questions, the serologic parameters which reflect the disease activity of RA and pulmonary function tests which reflect small airway dysfunction were performed on 36 lifetime nonsmokers with RA who had normal chest x-ray findings. The prevalence of SAD and the relationships between the disease activity parameters of RA and pulmonary function were observed. The results were as follows. The percentages of patients with abnormal values for diffusing capacity, frequency dependence of compliance (C1.0/C0.0), forced expiratory flow 25-75%, Vmax50% and Vmax 75% were 45.5%, 62.5%, 40%, 22.8% and 11.4%, respectively. There was statistically significant negative correlation between C1.0/C0.0 and ESR. But consistent correlation between other pulmonary function tests and clinical and serologic parameters of RA, and differences in pulmonary function between patients who were serologically positive and negative for CRP and FANA, were not found. In conclusion, SAD, without the influence of smoking, is frequently associated with RA, but the presence of SAD cannot be predicted from any clinical and serologic parameters of RA currently in use.
8730124 Inorganic pyrophosphate generation from adenosine triphosphate by cell-free human synovial 1996 Apr OBJECTIVE: To quantify inorganic pyrophosphate (PPi) production from extracellular adenosine triphosphate (ATP) by human synovial fluids (SF). METHODS: Serial measurements of ATP hydrolysis rate (t1/2) were performed by the luciferase method from a starting concentration of 500 nM in 21 pathologic and one normal cell-free SF samples incubated under physiologic conditions. ATP was then pumped into a sample of each fluid, using the rate constant derived from the t1/2 of that fluid, to provide steady state levels simulating those reported in SF. Trace [32P] gamma ATP was added at the start of the infusion; conversion to [32P] Pi and to [32P] PPi was determined by precipitation of Pi as reduced phosphomolybdate before and after treatment with yeast inorganic pyrophosphatase. Finally, the pumping experiment was repeated and PPi production was calculated from direct measurement of PPi at time zero and at 60 min. PPi hydrolysis was measured in each fluid by [32P] Pi precipitation from [32P] PPi tracer added at time zero. RESULTS: ATP was hydrolyzed by all SF. The mean t1/2 (seconds) in 8 osteoarthritis (OA) samples was 72 s, in 5 calcium pyrophosphate dihydrate (CPPD) 30 s (p < 0.02), in 3 rheumatoid arthritis (RA) 1160 s, in normal 86 s, in 3 olecranon bursal (OB) 54 s, and in 2 total knee replacement fluid samples 17 and 121 s. The major product of ATP hydrolysis was PPi in all but 2 fluids (1 RA, 1 OB), even at lower than steady state levels. At simulated in vivo steady state ATP levels, mean conversion of APT to PPi was stoichiometric in OA and CPPD fluids. PPi hydrolysis was < 4% in all noninflammatory fluids. CONCLUSION: PPi is the major product of extracellular ATP catabolism in most SF. Hydrolysis rates were significantly faster in SF containing CPPD crystals. Mean PPi production by these fluids at simulated in vivo steady state levels was 6-fold that of OA SF (p < 0.01). Hydrolysis of extracellular ATP by ectonucleotide pyrophosphohydrolases can account for all PPi produced by joint issues previously estimated from [32P] PPi pool and turnover studies in human knee joints.
1476011 Association of rheumatoid arthritis with Kartagener's syndrome in a patient with HLA-DR1-D 1992 Sep A case of severe seropositive rheumatoid arthritis associated with Kartagener's syndrome in a patient positive for B27, DR4, and DR1 has been presented. A number of immunological disturbances were observed, especially defective granulocyte function and depressed delayed hypersensitivity.
8055200 The incidence of rheumatoid arthritis in the United Kingdom: results from the Norfolk Arth 1994 Aug This paper provides the first data on the incidence of RA based on a prospective population-based register. All new cases of inflammatory polyarthritis in the Norwich Health Authority are notified by general practitioners to the Norfolk Arthritis Register. The patients are then clinically evaluated by metrologists and blood taken for RF estimation. Cases of RA were defined as all those notified with an onset of symptoms in 1990; who presented by 31 December 1991; and who satisfied the 1987 ARA criteria for RA at the time of presentation. Two hundred and ten patients were notified in the defined time-frame, of whom 104 were classified as having RA. The annual incidence rate was 36/100,000 for women and 14/100,000 for men. RA was rare in men aged under 45 yr. The incidence in men rose steeply with age. The incidence in women rose up to age 45 yr, plateaued to age 75 yr, and fell in the very elderly.
8182623 Erosive rheumatoid factor negative and positive rheumatoid arthritis are immunogenetically 1994 Feb OBJECTIVE: The relationship between rheumatoid factor positive (RF+) and rheumatoid factor negative (RF-) rheumatoid arthritis (RA) is controversial. We sought to determine whether the HLA genes conferring susceptibility for erosive RF+RA are also prevalent in patients with erosive RF-RA. METHODS: DNA-based HLA typing for DRB1, DQB1, and DPB1 was performed on 16 consistently RF--patients with erosive RA. RESULTS: Thirteen of 16 (81%) RF-RA patients had the HLA susceptibility genes DRB1 *0401, *0404, or *0101, which are associated with RF+RA, as compared to 46% of normal controls (p = 0.017). By contrast, no associations with HLA-DQB1 and HLA-DPB1 alleles were apparent. CONCLUSION: Specific HLA susceptibility alleles are prevalent in patients with erosive RA, regardless of RF status, suggesting a similar immunogenetic basis for RA in these patients.
8838502 Antineutrophil cytoplasmic antibodies in synovial fluid and in serum of patients with rheu 1996 Jan OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are present in several vasculitides and in other immunomediated diseases. The reported prevalence of ANCA in rheumatoid arthritis (RA) is variable. In addition, the presence of such autoantibodies has been poorly investigated in synovial fluid (SF). The objectives of this study were (1) to investigate the presence of ANCA both in the serum and in SF from patients with RA and other forms of synovitis (OS); (2) to analyze the reactivity of ANCA against isolated antigens proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF); and (3) to evaluate the clinical relevance of these autoantibodies. METHODS: Twenty-eight patients with RA, 13 with OS, and 17 with osteoarthritis (OA) of the knee joint were studied. No patient had clinical manifestations of vasculitis. SF and serum samples were investigated for the presence of ANCA by indirect immunofluorescence (IIF); the reactivity against PR3, MPO and LF was assessed by ELISA. RESULTS: ANCA were detected by IIF in SF of 39.3% patients with RA, 38.5% with OS, and 5.9% with OA. With 2 exceptions, patients who had ANCA in SF showed positivity also in serum. The presence of both anti-MPO and anti-LF antibodies was found in 3 patients with RA and 1 with OA; a patient with RA showed antibodies only against LF and another one with RA only against MPO. No reactivity was found against PR3. In patients with RA ANCA were not associated with disease activity. CONCLUSION: We found an increased incidence of ANCA both in SF and serum from patients with RA and OS. The pathogenic role and the clinical relevance of such autoantibodies in these diseases remain to be established.