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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
9159532 Enhanced co-stimulatory ability of synovial fluid accessory cells in rheumatoid arthritis. 1997 Apr We have established in vitro assays that allow the examination of co-stimulatory function of rheumatoid arthritis (RA) antigen-presenting cells (APC). Synovial fluid (SF) and peripheral blood (PB) APC co-stimulatory ability was compared in the activation of peptide-specific human T-cell clones. T-cell receptor (TCR) stimulation by peptide or anti-CD3 antibody allowed the direct comparison of SF and PB APC co-stimulatory activity, separately from their ability to process antigen. SF APC from 15 RA patients consistently enhanced T-cell proliferation when compared to their PB counterparts. Moreover, increasing the numbers of PB APC present resulted in only a minor increase in T-cell proliferation, failing to achieve levels stimulated by SF APC. We propose that the enhanced co-stimulatory function of synovial APC may be a significant factor in the persistence of local immune responses in RA.
10217559 Primary juxtaarticular soft tissue lymphoma arising in the vicinity of inflamed joints in 1999 Mar AIMS: Primary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein. METHODS AND RESULTS: The clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein-Barr virus (EBV) encoded RNA (EBER). All three patients were females with a long-standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti-inflammatory drugs and one also received gold, penicillamine and intra-articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B-cell lymphomas. None were associated with EBV as determined by in situ hybridization. CONCLUSIONS: These cases document an association between rheumatoid arthritis and soft tissue lymphoma of B-cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV-positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy.
11845436 The influence of synovial fluid on lymphocyte functions in rheumatoid arthritis. 1998 Jul Rheumatoid arthritis (RA) is a chronic recurrent and systemic inflammatory disease affecting around 1% of the population, that primarily involves the joints. In this study, we determined the Th1/Th2 lymphocytes ratio at the site of rheumatoid inflammation and the influence of the synovial fluid (SF) on the secretory and proliferative function in synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC), obtained from patients with RA. Our results showed significant differences concerning the mononuclear cells and the CD4/CD8 ratio in synovial fluid and peripheral blood of patients. In SF prevailed Th1 cells, while in peripheral blood we found another cytokine profile of T lymphocytes. Also synovial fluid lymphocytes had a low PHA-stimulated blastogenic response. Patients plasma and synovial fluid showed an inhibitory effect on prolipheration indexes.
9858424 HLA associations of seropositive rheumatoid arthritis in a Cree and Ojibway population. 1998 Dec OBJECTIVE: To determine the HLA associations of seropositive rheumatoid arthritis (RA) in a Cree and Ojibway population; to determine whether specific alleles distinguish juvenile or adult onset. METHODS: HLA-A, B, C, and DRB1 alleles were analyzed in 23 Ojibway and Cree patients with RA seen in a single tertiary care center. Comparisons were made with published results of controls and with results of 18 patients with rheumatoid factor (RF) positive polyarticular juvenile rheumatoid arthritis (JRA) from the same population. RESULTS: Comparisons among patients with RA, patients with RF positive polyarticular JRA, and controls showed increased frequencies of the RA shared epitope in patients with RA and of DRB1*0901 in patients with seropositive polyarticular JRA, while the frequency of DRB1*08 alleles was decreased in patients with RF positive polyarticular JRA. CONCLUSION: In this population, DRB1*0901 may promote while DRB1*08 alleles may protect against a juvenile onset of RA specifically. In contrast, the RA shared epitope may have a greater effect on the risk of adult onset seropositive RA. Due to the small patient numbers, these results require confirmation.
11307073 In vivo characterization of glenoid with use of computed tomography. 2001 Mar Improvement in the treatment of the shoulder could be achieved by accurately describing the pathologic characteristics of the joint. The goal of this study was to characterize, in vivo, glenoids with 3 different diagnoses by using computed tomography (CT): rotator cuff pathology with a limited rupture and without bony changes (group A, n = 15), primary osteoarthritis (group B, n = 13), and rheumatoid arthritis (group C, n = 4). The bone density distribution was assessed by means of the CT value expressed in Hounsfield units. The version angle was also measured. The examination of the CT value showed different distributions according to the pathology. In group A, the cancellous bone presented a central area with a relatively homogeneous and low density. In group B, the reinforcement of the density along with the posterior region seemed to be correlated with the retroversion angle. In the rheumatoid arthritis group, the main characteristic was the loss of the subchondral bone margin. The cartography of the CT value was not reproducible among the 4 cases examined. These in vivo descriptions provide guidelines for the surgeon before total shoulder arthroplasty, helping preoperative planning as well as simulation of implantation.
9779304 Urine levels of type 1 collagen cross-linked N-telopeptides and deoxypyridinoline correlat 1998 Sep OBJECTIVES: The aim of this study was to find out whether spot urinary concentrations of type 1 collagen cross-linked N-telopeptides (NTx) and deoxypyridinoline (Pyrilinks-D) can differentiate between active and inactive disease in rheumatoid arthritis (RA) and to investigate the extent to which they correlate with indices of disease activity. METHODS: Using enzyme-linked immunosorbent assays, the concentrations of NTx and Pyrilinks-D were estimated in spot urine samples from 25 females with active disease, 25 females with inactive disease, and in 25 controls. RESULTS: In Patients with active disease, urinary concentrations of NTx and Pyrilinks-D were significantly higher (p < 0.01) than in those with inactive disease or in healthy controls. In active disease there were significant positive correlation between urinary NTx and ESR, the swollen joint count, the tender joint count, and the patient's global assessment.
10381063 Successful treatment of methotrexate induced nodulosis with D-penicillamine. 1999 Jun Accelerated nodulosis is a recognized complication of methotrexate (MTX) therapy in rheumatoid arthritis (RA). We describe 3 patients with accelerated nodulosis treated with D-penicillamine (D-Pen) while continuing MTX. The combination of D-Pen with MTX therapy resulted in regression of subcutaneous nodules in all patients, disappearance of pulmonary nodules in one patient, and resolution of vasculitic lesions in 2 patients. Clinical response was observed within the first few weeks of therapy and usually required moderate doses (500 mg/day). Our observations suggest that addition of D-Pen to MTX therapy can be an alternative therapeutic option for accelerated nodulosis in patients with RA.
9246112 [Diagnostic value of the HLA phenotype in inflammatory rheumatic diseases]. 1997 Jun 28 OBJECTIVES: HLA phenotyping is usually considered as costly and unnecessary for the diagnosis of inflammatory rheumatoid diseases. The aim of our work was to assess the diagnostic value of HLA phenotyping compared with the diagnostic value of sex and age at the onset of disease in cases where there is a doubt between rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement. METHODS: The relative prevalence of inflammatory rheumatoid diseases was calculated for 138 patients hospitalized for diagnosis of rheumatoid disease. We considered however that in these patients the etiology of the inflammatory rheumatoid disease with synovitis, after search for etiology, could be either spondyloarthropathy with peripheral involvement or early-stage rheumatoid polyarthritis. Positive and negative predictive values were calculated by comparison between these two diseases. The sensitivity of HLA B27 in spondyloarthropathy with peripheral involvement was determined in a population of 83 hospitalized patients with confirmed diagnosis. The prevalence of HLA DR4 in rheumatoid polyarthritis was determined in 375 hospitalized patients with confirmed diagnosis. Predictive values were calculated using Bayes formula. RESULTS: The analysis of the positive and negative predictive values for HLA B27 showed that the diagnostic value of this allele was much greater than age at disease onset and sex in spondyloarthropathy with peripheral involvement. For rheumatoid arthritis, comparison of the diagnostic value of HLA DR4 versus age at disease onset and sex showed the lower performance of HLA DR4. However, the positive predictive value of HLA DR4 in rheumatoid polyarthritis was similar to that for these factors and equivalent to that of HLA B27. The positive predictive value for the combinations HLA DR4+ HLA B27- and HLA B27+ HLA DR4- was 0.90 for rheumatoid polyarthritis and spondyloarthropathy with peripheral involvement respectively. CONCLUSION: The validity of these promising findings should be confirmed in prospective studies.
9389221 Reduced cortical responses to noxious heat in patients with rheumatoid arthritis. 1997 Oct OBJECTIVES: To test the hypothesis that patients with chronic inflammatory pain develop adaptive cortical responses to noxious stimulation characterised by reduced anterior cingulate responses. METHODS: Positron emission tomography was used to measure changes in regional cerebral blood flow (rCBF) in response to an acute experimental pain stimulus in six patients with rheumatoid arthritis (RA) in comparison to six age and sex matched controls. A standardised and reproducible non-painful and painful phasic heat stimulus was delivered by a thermal probe to the back of the right hand during six two minute periods during which time rCBF measurements were made. The effects of non-painful heat were subtracted from those of painful heat to weight the analysis towards the non-discriminatory or 'suffering' components of pain processing. Significance maps of pain processing were generated and compared in each group and contrasted with results obtained in a group of patients with atypical facial pain (AFP) that have been previously published. RESULTS: The RA patients showed remarkably damped cortical and subcortical responses to pain compared with the control group. Significant differences between the two groups were observed in the prefrontal (BA 10) and anterior cingulate (BA 24) and cingulofrontal transition cortical (BA 32) areas. The reduced anterior cingulate responses to standardised heat pain were compared with the increased cingulate responses seen in patients with psychogenically maintained pain (AFP) who had both lower pain tolerance and mood than the RA group. CONCLUSIONS: Major cortical adaptive responses to standardised noxious heat can be measured and contrasted in patients with different types of chronic pain. The different pattern of cingulate and frontal cortical responses in the patients with inflammatory and non-nociceptive pain suggest that different mechanisms are operating, possibly at a thalamocortical level. Implications for treatment strategies for chronic pain are discussed.
11177775 COX-2 inhibitors in rheumatoid arthritis. 2001 Feb The selective cyclooxygenase 2 (COX-2) inhibitors have emerged as an important option in the treatment of rheumatoid arthritis (RA). Rofecoxib and celecoxib, the selective COX-2 inhibitors currently available, have shown efficacy in reducing symptoms of RA comparable with that of traditional nonsteroidal antiinflammatory drugs (NSAIDs). The primary advantage of selective COX-2 inhibitors relates to reduced gastrointestinal (GI) toxicity. Gastroduodenal ulcers detected by endoscopy are markedly diminished in patients receiving selective COX-2 inhibitors versus those receiving NSAIDs. Moreover, unpublished data indicate that the risk of symptomatic and complicated ulcers is reduced by approximately half in patients prescribed rofecoxib or celecoxib. Despite these encouraging findings, selective COX-2 inhibitors have the potential for important adverse events such as impaired renal function, hypertension, and edema. Furthermore, clinicians must balance the competing demands of reducing GI risk while managing the increasing costs associated with selective COX-2 inhibitor use.
9734681 Sleep apnoea caused by rheumatoid arthritis. 1998 Aug Sleep apnoea syndrome (SAS) is a rarely documented, but possibly lethal, complication of the instability of the cervical spine in rheumatoid arthritis. Five patients with SAS of a central or peripheral origin are presented, and the problems of recognizing and diagnosing the syndrome are discussed. We hope that clinicians will become more aware of the existence and the different aetiologies of SAS, thus improving early recognition and appropriate treatment. Adequate treatment has proven to increase survival in peripheral SAS and seems to be successful in doing so in central SAS.
11561498 Technique for arthroscopic assisted revision hip arthroplasty. 2001 We describe a new technique in which the arthroscope is used to assist the preparation of the cement mantle for cemented revision hip arthroplasty. We present two case reports demonstrating the method and its rationale.
9380862 [Integrated role of computerized tomography and magnetic resonance imaging in identifying 1997 Jan Any cervical spine segment may be affected by rheumatoid arthritis, but destructive changes are most prominent at the craniocervical junction. Cervical involvement is a devastating complication of the disease, because of the risk of a range of neurological complications (paresthesia, cervical myelopathy, vertebro-basilar insufficiency), and even sudden death from medullary compression. However, the incidence of both cervical rheumatoid arthritis and its neurological complications are still debated, being respectively reported in 17-86% and 11-70% of the patients, according to the variability in neurological and radiologic classification systems adopted by the authors. To assess the incidence of cervical rheumatoid arthritis and the integrated role of different imaging techniques in its diagnosis, 38 consecutive patients (29 women and 9 men) with rheumatoid arthritis according to the American Rheumatism Association criteria were examined. The average age was 60 years (range: 27-70 years) with a mean disease duration of 6.6 years (range: 6 months-25 years). All the patients underwent conventional radiography of the cervical spine, unenhanced Computed Tomography (CT) of the craniocervical junction and unenhanced and Gadolinium-enhanced Magnetic Resonance Imaging (MRI) of the cervical spine. Cervical spine involvement was demonstrated in 25/38 (66%) patients 20 women and 5 men, with an average age of 57 years and a mean disease duration of 8.5 years. In 13 of them (mean disease duration: 12.7 years), the diagnosis was made with radiography which showed atlantoaxial and subaxial subluxations and/or erosions. Of the 12 patients with negative conventional radiography (mean disease duration: 2.5 years), 4 were identified with both CT and MRI (synovial pannus and erosions). 3 with MRI only (joint effusion/hypervascularized synovial pannus), and 5 exhibited questionable CT findings which were clarified only by MR demonstration of inflammatory tissue contiguous to suspicious irregularities of the cortical bone of the odontoid process. 52% (13/25) of cervical rheumatoid arthritis patients were identified with plain radiographs, 68% (17/25) with CT and 100% (25/25) with MRI. Our preliminary data show that a specific tool for the diagnosis is recommended even in the early disease phases since rheumatoid arthritis commonly affects the craniocervical junction. Studying the craniocervical region is clinically difficult, and diagnostic imaging assessment is essential. Conventional radiography allowed to detect more than half the patients with cervical rheumatoid arthritis, but only in advanced disease stages. On the contrary, MRI had the unique potential of direct and detailed synovial visualization, thus permitting the diagnosis of cervical involvement even in the early phases of the inflammatory process, when CT findings were still negative or questionable.
10685790 A single cell analysis of Fas ligand positive T cells in rheumatoid synovial fluid. 2000 Feb OBJECTIVE: To investigate the function of Fas ligand (Fas-L) positive T cells in rheumatoid synovium, we analyzed the T cell receptor (TCR) CDR3 region and examined the expression of cytokines in both Fas-L+ and Fas-L- single T cells. METHODS: Synovial fluid (SF) samples were collected from 2 patients with rheumatoid arthritis. TCR BV8+ T cells were sorted into a 96 well plate at a density of one cell per well. Expression of Fas-L, interferon-gamma, interleukin 2 (IL-2), IL-4, IL-6, and IL-10 was analyzed by reverse transcription-polymerase chain reaction and Southern blot and the TCR BV8 junctional region was sequenced. RESULTS: Twenty-two of 30 TCR BV8+ T cells from Patient 1 and 20 of 43 TCR BV8+ T cells from Patient 2 were Fas-L+ T cells, while the others were Fas-L-. Junctional sequence analysis showed the presence of some conserved amino acid motifs in the CDR3 region (SRQ, GFG, SSG, SGS, LGTSGTL, TLSS) in 13 clones of Fas-L+ T cells from Patient 1, whereas no conserved amino acid motif in Fas-L-T cells was found. In Patient 2, conserved amino acid motifs (PGQ, GQG, TTWGA) in the CDR3 region were found in 6 clones of Fas-L+ T cells, while only one was found in 2 clones of Fas-L-cells. In Fas-L+ T cells, 90-93% expressed both IL-2 and IL-10 mRNA. CONCLUSION: Fas-L+ TCR BV8+ T cells revealed the conserved amino acids motif in the CDR3 region, suggesting that Fas-L+ T cells might expand by antigen stimulation and play a crucial role as Th0-type T cells in triggering autoimmunity in rheumatoid synovium.
10743796 Phase I/II trial of recombinant methionyl human tumor necrosis factor binding protein PEGy 2000 Mar OBJECTIVE: To evaluate the safety, immunogenicity, pharmacokinetics, and efficacy of intravenous administration of tumor necrosis factor binding protein (TNFbp) dimer in patients with rheumatoid arthritis (RA). METHODS: This phase I/II study was a multicenter, randomized, double blind, placebo controlled, ascending dose study evaluating TNFbp dimer administered by i.v. infusion. Thirty-three patients with RA divided into 3 cohorts received TNFbp dimer (30, 100, 300 microg/kg) or placebo during a 5 min infusion at baseline and at 3 and 6 weeks; patients were followed at routine intervals after each infusion through 77 days postinfusion. Pharmacokinetics were analyzed using a log-linear regimen and comparisons were made between half-life after first, 2nd, and 3rd doses. Plasma TNFbp dimer concentrations and serum antibody levels were used in the measurement of pharmacokinetics. RESULTS: Administration of 30 microg/kg of TNFbp dimer was generally well tolerated; the maximum tolerated dose was 100 microg/kg. No serious adverse events were reported. A significant antibody response affected the half-life and clearance of TNFbp dimer at each dose group. Anti-TNFbp antibodies were noncytotoxic and nonagonistic. Clinical evaluations provided evidence of in vivo activity of TNFbp dimer in these patients. CONCLUSION: TNFbp dimer administered to patients with long standing RA resulted in significant antibody production to the study drug. This effect reduced the half-life and clearance of the TNFbp. This TNFbp will not be a viable option for treating patients with RA secondary to immunogenicity.
11323282 Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. 2001 May T-cell diversity is generated through the production of new thymic emigrants. Thymic function declines with age, and the T-cell pool is maintained through homeostatic proliferation of naive peripheral T cells. This article discusses the impact of thymic output and peripheral T-cell homeostasis on the development of rheumatoid arthritis (RA). It is proposed that thymic output is prematurely compromised in RA patients. A compensatory expansion of peripheral T cells results in a contracted and distorted repertoire, possibly favoring T cells with autoreactive potential. Increased risk of autoimmunity, as a consequence of abnormal T-cell population dynamics, could be a common mechanism in chronic inflammatory diseases.
9779839 Intention-to-treat analysis of 200 patients with rheumatoid arthritis 12 years after rando 1998 Oct OBJECTIVE: To assess existing disease modifying antirheumatic drugs (DMARD) using a strategy aiming for sustained suppression of inflammation. METHODS: We conducted intention-to-treat analysis of open randomized study [sulfasalazine (SASP) or penicillamine (PEN)], followup 12 years, conducted at specialist rheumatology clinics in Glasgow, Scotland. Subjects were 200 patients with rheumatoid arthritis (RA) with established disease. In this "true to life" approach, comorbidity was not an exclusion criterion unless it prejudiced assessment of drug toxicity. The main outcome measure was the Health Assessment Questionnaire (HAQ) functional score. RESULTS: Over 12 year followup 95 (47.5%) patients died; this was the commonest reason for study groups being unfulfilled. There was one drug related death (methotrexate). Patients who were socially disadvantaged were more likely to die prematurely. HAQ did not deteriorate significantly in those who continued taking their original DMARD, or in the SASP intention-to-treat group over 12 years. Sustained suppression of disease activity was possible in the entire group available for followup at 12 years. Most toxicity occurred early and no unexpected side effects were observed. CONCLUSION: High premature mortality in RA was confirmed and an association between mortality and deprivation was demonstrated. Sustained reduction in acute phase response was possible using sequential single DMARD. This study provides useful baseline and longterm information against which to evaluate combination therapy or new agents.
10640775 Evidence for common autoimmune disease genes controlling onset, severity, and chronicity b 2000 Feb 1 The pathogenicity of multiple sclerosis is still poorly understood, but identification of susceptibility genes using the animal model experimental allergic encephalomyelitis (EAE) could provide leads. Certain genes may be shared between different autoimmune diseases, and identification of such genes is of obvious importance. To locate gene regions involved in the control of EAE and to compare the findings with the susceptibility loci recently identified in a model for rheumatoid arthritis (pristane-induced arthritis), we made crosses between the encephalomyelitis- and arthritis-susceptible rat strain DA and the resistant E3 strain. Genetic analysis of animals produced in a F2 intercross identified 11 loci associated with specific EAE-associated traits. Interestingly, five of these loci were situated at the same position as major loci controlling pristane-induced arthritis and showed similarities in inheritance pattern and subphenotype associations. Our results show that different phases of EAE are controlled by different sets of genes and that common genes are likely to be involved in different autoimmune diseases.
10342628 MIA (melanoma inhibitory activity): a potential serum marker for rheumatoid arthritis. 1999 Feb OBJECTIVE: MIA (melanoma inhibitory activity) is correlated with metastasis in patients with malignant melanoma. As MIA is not only produced by melanoma cells, but also by differentiated chondrocytes, we examined whether serum levels of MIA are correlated with inflammation and/or joint destruction in rheumatic diseases. METHODS: MIA serum concentrations of patients with different rheumatic diseases were examined and compared with healthy individuals and malignant melanoma patients. In addition, MIA concentrations were correlated to inflammatory parameters and joint destruction. RESULTS: Increased MIA serum concentrations were found only in patients with rheumatic diseases associated with joint destruction, such as rheumatoid arthritis (RA), osteoarthritis, HLA B27-associated oligoarthritis, and psoriatic arthritis. Of these rheumatic diseases, a significant increase in MIA serum concentrations was seen only in patients with RA, associated with rheumatoid factor (RF) positivity and joint destruction. CONCLUSIONS: In addition to RF, MIA might therefore be useful in the differential diagnosis of RA vs non-destructive rheumatic diseases, and the presence of elevated levels of MIA in serum very likely reflects joint destruction in RA.
11302883 Isolated digital vasculitis in a patient with rheumatoid arthritis: good response to tumou 2001 May Tumour necrosis factor alpha (TNFalpha) blocking agents are among the most promising new treatments for rheumatoid arthritis (RA). However, no data exist about the effect of these agents on extra-articular manifestations of RA. A patient is described with small vessel vasculitis that repeatedly responded well to treatment with the soluble p55 TNFalpha receptor fusion protein Ro 45-2081 (lenercept).