Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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11869637 | Thermotherapy for treating rheumatoid arthritis. | 2002 | BACKGROUND: Thermotherapy is often used as adjunct in the treatment of rheumatoid arthritis (RA) by rehabilitation specialists. OBJECTIVES: To evaluate the effectiveness of different thermotherapy applications on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: We searched Medline, EMBASE, Pedro, Current Contents, Sports Discus and CINAHL up to and including September 2001. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Hand searching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials, controlled clinical trials, cohort studies or case/control studies, of thermotherapy compared to control or active interventions in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search (VR, LB). These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Seven studies (n=328 subjects) met the inclusion criteria. The results of this systematic review of thermotherapy for RA found that there was no significant effect of hot and ice packs applications (Ivey 1994), cryotherapy (Rembe 1970) and faradic baths (Hawkes 1986) on objective measures of disease activity including joint swelling, pain, medication intake, range of motion (ROM), grip strength, hand function compared to a control (no treatment) or active therapy. There is no significant difference between wax and therapeutic ultrasound as well as between wax and faradic bath combined to ultrasound for all the outcomes measured after 1, 2 or 3 week(s) of treatment (Hawkes 1986). There was no difference in patient preference for all types of thermotherapy. No harmful effects of thermotherapy were reported. REVIEWER'S CONCLUSIONS: Superficial moist heat and cryotherapy can be used as a palliative therapy. Paraffin wax baths combined with exercises can be recommended for beneficial short term effects for arthritic hands. These conclusions are limited by methodological considerations such as the poor quality of trials. | |
12236619 | Examining the efficacy of biologic therapy: are there real differences? | 2002 Sep | Biologic therapy with anakinra, etanercept, and infliximab effectively reduced the signs and symptoms of active rheumatoid arthritis (RA) in randomized controlled trials. Clinical efficacy was determined by American College of Rheumatology (ACR) response criteria. In patients failing previous disease modifying antirheumatic drug (DMARD) therapy, both anakinra and etanercept were significantly more effective than placebo. In patients with inadequate responses to methotrexate (MTX), addition of anakinra, etanercept, or infliximab to stable MTX therapy was significantly more effective than MTX alone. Etanercept has also shown efficacy in early stage, methotrexate-naive patients. Comparisons of the efficacy of these biologics across clinical studies are problematic due to differences in study design, study conduct, and patient populations. Moreover, ACR response rates do not allow comparisons of agents that each achieve these responses relative to placebo. Until comparative clinical studies are conducted, in which 2 biologics are evaluated using the same protocol and patient population, the only conclusion that can be reached from published studies is whether an individual biologic agent is safe and effective. All 3 biologics - anakinra, etanercept, and inflixmab - are effective. | |
15040811 | Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis | 2004 Feb 17 | BACKGROUND: Extracts of Tripterygium wilfordii Hook F (TWHF), a traditional Chinese herb, have been reported to show efficacy in patients with rheumatoid arthritis (RA). Since RA is not only characterized by inflammation but also by synovial proliferation in the joints, we examined whether triptolide (a constituent of TWHF) could influence the proliferation of rheumatoid synovial fibroblasts (RSF) by induction of apoptosis. RESULTS: RSF were obtained from RA patients during surgery and were treated with triptolide under various conditions. The viability and proliferation of RSF were measured by the 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay and by 5-bromo-2'-deoxyuridine incorporation, respectively. Apoptosis was identified by detection of DNA fragmentation using an enzyme-linked immunosorbent assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). The role of caspases in apoptosis of RSF was analyzed by measuring caspase-3 activity. Activation of the peroxisome proliferator-activated receptor (PPAR) gamma was assessed by a luciferase reporter gene assay using RSF transfected with a plasmid containing the peroxisome proliferator response element. Triptolide decreased viability, inhibited proliferation, and induced apoptosis of RSF in a concentration-dependent manner at very low (nM) concentrations. Caspase-3 activity was increased by treatment with triptolide and was suppressed by caspase inhibitors. Although PPARgamma activation was induced by 15-deoxy-Delta12,14-prostaglandin J2, triptolide did not induce it under the same experimental conditions. An extract of TWHF also induced DNA fragmentation in RSF. CONCLUSION: The mechanism of action remains to be studied; however, triptolide may possibly have a disease-modifying effect in patients with RA. | |
12910563 | Assessment of depression in rheumatoid arthritis: a modified version of the center for epi | 2003 Aug 15 | OBJECTIVE: The Center for Epidemiologic Studies Depression Scale (CES-D) is an instrument commonly used to assess depressive symptoms. Although the psychometric properties of the instrument are well established, the instrument's ability to identify confirmed cases of major depression has been unclear. The purpose of this study was to evaluate the ability of cutoff scores from both a full scale and a modified CES-D to detect major depression in people with rheumatoid arthritis (RA). METHOD: Data were analyzed from 457 persons with RA, including 91 who met criteria for major depression. RESULTS: Results indicated that, in general, a full scale cutoff score of 19 was the most efficient in identifying cases of major depression; the cutoff score of 19 outperformed a variety of other cutoff scores from the modified scale. Even the most efficient cutoff scores, however, demonstrated problems in accurately identifying people with depression. CONCLUSION: The CES-D, while potentially useful as a screening tool, should not be used to identify cases of major depression. | |
12209504 | Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence f | 2002 Aug | OBJECTIVE: The pathogenetic role of B cells in rheumatoid arthritis (RA) is under debate, but it is currently believed to be marginal. The availability of selective anti-B cell treatment provides a unique opportunity to clarify this issue. This study was undertaken to investigate the effects of B cell blockade in the treatment of refractory RA, and to evaluate the implications with regard to the role of B cells in the disease. METHODS: Five female patients with active, evolving erosive RA were treated with rituximab, an anti-CD20 chimeric monoclonal antibody. All 5 patients had been nonresponders to combination therapy with methotrexate plus cyclosporin A. Two of the 5 had also failed to respond to anti-tumor necrosis factor alpha therapy. All of these treatments were discontinued 1 month before institution of anti-CD20 therapy. RESULTS: Marked clinical improvement was observed in 2 patients (American College of Rheumatology 70% response [ACR70] and ACR50, respectively), starting at the end of the second month after institution of anti-CD20 therapy (month 2) and lasting until month 10 in 1 patient (articular relapse) and month 12 in the other (last followup). ACR20 response was observed in 2 additional patients, lasting until month 5 and month 7, respectively (articular relapse in both). Decrease or normalization of serum C-reactive protein and rheumatoid factor levels were observed in these patients. In contrast, patient 3 had no response to the treatment. RA synovitis and evolving erosive damage were decreased in patients exhibiting a major response, as demonstrated by imaging studies. CONCLUSION: Our finding of the clinical efficacy of selective B cell blockade indicates that B cells play a critical role in rheumatoid synovitis, at least in a subset of patients. Qualitative or quantitative differences in B cell commitment in RA pathobiology might have a function in the different responses observed. | |
14517699 | Ultrasound detection of bone erosions in rheumatoid arthritis: a comparison to routine rad | 2004 Feb | PURPOSE: To determine if ultrasound (US) of selected joints in the hands and feet can detect more erosions than radiography and establish the presence of erosive disease in patients with rheumatoid arthritis (RA). METHODS: Eighty joints in ten patients with RA and 40 joints in five healthy control subjects, who were age, gender and ethnicity-matched to the patients with arthritis, were prospectively studied with radiographs and sonography. Conventional radiographs of the hands and feet were obtained. US examinations of the 2nd and 5th metacarpal-phalangeal (MCP) joints of the hands, and the 1st and 5th metatarsal-phalangeal (MTP) joints of the feet were performed. Radiographs and US exams were independently graded for the presence of erosions. RESULTS: None of the control subjects had erosions. US detected erosions in 17/80, and radiographs detected erosions in 6/80 joints assessed with both modalities. US detected all erosions seen by radiographs in these selected joints. Erosive disease was present in the radiographs of seven of ten RA patients. US established erosive disease in eight of ten RA patients. US determined erosive disease in two of the three patients without radiographic erosions. CONCLUSIONS: US of the MTP and MCP joints in RA can detect erosions not seen with radiography and may be complementary to radiography in establishing the presence of erosive disease in early RA. | |
15280421 | Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TN | 2004 Aug 2 | Regulatory T cells have been clearly implicated in the control of disease in murine models of autoimmunity. The paucity of data regarding the role of these lymphocytes in human autoimmune disease has prompted us to examine their function in patients with rheumatoid arthritis (RA). Regulatory (CD4(+)CD25(+)) T cells isolated from patients with active RA displayed an anergic phenotype upon stimulation with anti-CD3 and anti-CD28 antibodies, and suppressed the proliferation of effector T cells in vitro. However, they were unable to suppress proinflammatory cytokine secretion from activated T cells and monocytes, or to convey a suppressive phenotype to effector CD4(+)CD25(-) T cells. Treatment with antitumor necrosis factor alpha (TNFalpha; Infliximab) restored the capacity of regulatory T cells to inhibit cytokine production and to convey a suppressive phenotype to "conventional" T cells. Furthermore, anti-TNFalpha treatment led to a significant rise in the number of peripheral blood regulatory T cells in RA patients responding to this treatment, which correlated with a reduction in C reactive protein. These data are the first to demonstrate that regulatory T cells are functionally compromised in RA, and indicate that modulation of regulatory T cells by anti-TNFalpha therapy may be a further mechanism by which this disease is ameliorated. | |
12966595 | The effect of ingestion of ferrous sulfate on the absorption of oral methotrexate in patie | 2003 Sep | OBJECTIVE: To investigate if ingestion of ferrous sulfate, 300 mg twice daily, will reduce the urinary excretion of unmetabolized methotrexate (MTX) in patients with rheumatoid arthritis (RA) who ingest 2 drugs concurrently, and determine if ferrous sulfate interferes with the absorption of oral MTX. METHODS: In this randomized double-blind placebo controlled crossover study, we compared the urinary excretion of unmetabolized MTX in 10 patients with RA who ingested 7.5 mg MTX as their weekly dose and took either ferrous sulfate 300 mg twice daily or placebo. RESULTS: Ten patients with RA taking 7.5 mg MTX orally once weekly had an average 24 h urine excretion of MTX (while taking 300 mg ferrous sulfate twice daily for one week) of 8.44 micromoles compared to 7.65 micromoles for patients taking placebo. The difference was not statistically significant (p = 0.50). CONCLUSION: Our results showed no less absorption of MTX for the placebo group compared to the group that took ferrous sulfate. These results do not support the hypothesis that ferrous sulfate interferes with the absorption of oral MTX. | |
12455815 | No association of polymorphisms of the CTLA-4 exon 1(+49) and promoter(-318) genes with rh | 2002 | The aim of this study is to investigate the significance of the polymorphisms of the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) exon 1(+49) and promoter(-318) genes in rheumatoid arthritis (RA). Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the CTLA-4 exon 1(+49) and promoter(-318) in 86 RA patients and 86 healthy control subjects. There was no significant difference in genotype, allele and phenotype frequencies of the CTLA-4 exon 1(+49) and promoter(-318) genes between RA patients and control subjects. There was no significant difference in age at onset, severity, functional class (> or = 3), physician global assessment, ESR, CRP or RF titer in patients with RA according to the CTLA-4 polymorphisms. Our data show that the polymorphisms within the CTLA-4 exon 1(+49) and promoter(-318) genes are not associated with susceptibility to RA and its clinical/serological manifestations in the Korean population. | |
12037598 | Possible association of non-binding of HSP70 to HLA-DRB1 peptide sequences and protection | 2002 May | The beta-chains of HLA-DR molecules associated with susceptibility to rheumatoid arthritis (RA) share a common amino acid sequence in their third hypervariable region at position 70-74. This shared epitope could either contribute to preferential binding of a given disease-associated peptide, be involved in disease-induction by molecular mimicry or, by binding to heat shock proteins, influence antigen presentation. It is known that the Escherichia coli M(r)70,000 heat shock protein DnaK can bind peptides from the shared epitope. Using a highly sensitive method, we show that peptides covering the third hypervariable region of associated, but also most of the non-associated HLA-DR alleles, bind to DnaK. Similar binding specificities could be found for the constitutively expressed mammalian M(r)70,000 heat shock protein Hsc73 and the inducible mammalian Hsp72. However, peptides containing the amino acid sequence DERAA, found in HLA-DR alleles and strongly associated with protection from RA, did not bind any HSP70. Thus, our results suggest a possible association of non-binding of HSP70 to HLA-DR molecules or its 70-74 fragments and protection from RA. | |
11959763 | Pregnancy and oral contraceptive use do not significantly influence outcome in long term r | 2002 May | BACKGROUND: Oral contraceptives (OC) and pregnancy are known to have an influence on the risk of onset of rheumatoid arthritis (RA). Pregnancy itself has beneficial effects on the activity of the disease, with relapses post partum. It is not known, however, whether OC and pregnancies influence the ultimate outcome of RA. OBJECTIVES: To explore whether OC use and pregnancies influence the 12 year outcome in RA as measured by radiological damage and disability. METHODS: In a prospective inception cohort of 132 female patients with recent RA according to the 1987 American College of Rheumatology criteria-a cohort initially gathered to study the association between hormonal factors and the onset of RA-outcome was assessed in a follow up after 12 years. The outcome was evaluated in 112 (85%) women by the radiological damage of hands and feet as measured with the Sharp score modification van der Heijde (SHS), the damage of the large joints measured with the Larsen score (LS) of large joints (0-60), and the disability measured with the Health Assessment Questionnaire (HAQ). The median values of each outcome variable were calculated for several subgroups of patients stratified for OC use and pregnancies before and after onset of the disease and the tertiles of the total number of months of OC use and of pregnancies. The association of OC use and pregnancies before and after onset of the disease with the outcome variables was calculated using Spearman's rank correlation (r(s)). The combined influence of OC use and pregnancies on the SHS, LS, and HAQ at 12 years was estimated using ordinal polytomous logistic regression. RESULTS: The median values of the SHS, LS, and HAQ showed a trend towards less radiological joint damage and less disability in women with long term OC use and multiple pregnancies. This difference, however, was not significant, except for the HAQ score in women with three or more pregnancies in life. There was no association between pregnancies, however defined, and any parameter of RA outcome after 12 years (maximum r(s)=-0.10). The only significant correlation was found between OC use before symptom onset and the LS (r(s)=-0.22, p<0.05). The combination of hormonal variables explained no more than a maximum of 3% of the variance of the 12 year outcome as measured by the SHS. CONCLUSION: OC use and pregnancy do not significantly influence outcome in long term RA. There is, however, a trend for patients with multiple pregnancies and long term OC use to have less radiographic joint damage and a better functional level. | |
15576259 | Illness-specific and general perceptions of social relationships in adjustment to rheumato | 2004 Dec | BACKGROUND: Adjustment to rheumatoid arthritis (RA) may be made more difficult when patients are unable to meet the expectations of family and friends about how well they are coping. PURPOSE: This study investigated the influence of illness-specific interpersonal expectations and general indices of social interactions on depressive symptoms among 39 women with RA (M age = 46.9 years; M disease duration = 11.2 years). METHODS: Female patients with RA and their spouses were recruited from an outpatient rheumatology clinic at an urban university hospital. Participants completed questionnaires at home and returned them to the research staff in prepaid, stamped envelopes. RESULTS: Results showed a significant correlation between spousal expectations and patients' perceived inability to meet them. Further, hierarchical regression analyses indicated that even when controlling for disease severity and traditional measures of social interactions (e.g., social support, perceived criticism, and general quality of the dyadic relationship), patient's perceived inability to meet spousal expectations contributed unique variance in depressive symptoms. CONCLUSIONS: These results suggest that adjustment to RA is not due entirely to the general features of social relationships, but additionally reflect specific aspects of the chronic illness milieu where spousal expectations and the patient's perceived inability to meet them are also related to adjustment. | |
15643571 | Quantification of bone lesions in rheumatoid arthritis by MRI multispectral tissue class t | 2004 Dec | Recent advances in the development of disease-modifying antirheumatic drugs (DMARDs) bring hope for a treatment that will provide inhibition of the structural damage associated with the disease. DMARD development presents great challenges for the validation of structural surrogate markers to evaluate the performance of these new therapies in clinical trials, where they will likely be compared with active controls. These challenges are being addressed in part by the medical imaging community by developing quantitative measures of RA disease progression for evaluation of new treatments during clinical trials. Recently, a novel multispectral (MS) MRI analysis method was presented to quantify temporal changes in bone lesions observed in the hands of RA patients. This technique employs image registration and MS analysis to identify MS tissue class transitions between serial MRI exams. This review will examine the use of MS class transition analysis as a means to quantify changes in bone lesions in the hands and wrists of patients with RA. | |
12422553 | [Identification, during development, of a methodology targeted at determining the position | 2002 Jul | The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned. | |
15188355 | Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovi | 2004 Jun | OBJECTIVE: To evaluate the regulation of acute-phase serum amyloid A (A-SAA) production in inflamed synovial tissue, and to elucidate a possible pathophysiologic role in the induction of matrix metalloproteinase (MMP) release by fibroblast-like synoviocytes (FLS). METHODS: Synovial tissue samples were obtained by arthroscopic biopsy from the knee joints of patients with inflammatory arthritis. Primary cultures of FLS from patients with rheumatoid arthritis (RA), psoriatic arthritis, sarcoid arthritis, and undifferentiated arthritis were established. Total RNA was extracted from FLS and analyzed by reverse transcription-polymerase chain reaction (PCR) using specific primers for A-SAA and formyl peptide receptor-like 1 (FPRL1), an A-SAA receptor. Southern blot analysis confirmed the PCR products generated. Immunohistochemical analysis demonstrated the expression of A-SAA protein production by several synovial cell populations, and immunofluorescence analysis confirmed A-SAA colocalization with the macrophage marker CD68. Primary FLS cultures stimulated with recombinant human A-SAA resulted in dose-dependent MMP-1 and MMP-3 production, as measured by an enzyme-linked immunosorbent assay. RESULTS: A-SAA messenger RNA (mRNA) and FPRL1 mRNA were present in FLS, macrophages, and endothelial cells isolated from the synovial tissue of patients with RA and other categories of inflammatory arthritis. A-SAA expression was regulated by proinflammatory cytokines and occurred in association with FPRL1 expression in FLS and endothelial cells, which is consistent with a biologic role at the sites of inflammation. Recombinant human A-SAA induced both MMP-1 and MMP-3 secretion by FLS. The mean fold increases in A-SAA-induced MMP-1 and MMP-3 production were 2.6 and 10.6, respectively, compared with 7.6-fold and 41.9-fold increases in interleukin-1 beta-induced MMP-1 and MMP-3 production. CONCLUSION: The up-regulation of the A-SAA and FPRL1 genes in inflamed synovial tissue suggests an important role in the pathophysiology of inflammatory arthritis. A-SAA induces the production of MMPs. Therapeutic targeting of A-SAA, or FPRL1, may modulate pathophysiologic pathways that are associated with matrix degradation in patients with RA and other forms of progressive inflammatory arthritis. | |
12193494 | Cricoarytenoid arthritis: a cause of acute upper airway obstruction in rheumatoid arthriti | 2002 Aug | PURPOSE: To report acute upper airway obstruction due to cricoarytenoid arthritis, a well known but uncommon complication of rheumatoid arthritis. CLINICAL FEATURES: We report the case of a 70-yr-old female scheduled for a colostomy who had been suffering from rheumatoid arthritis for 17 years. Preoperative history and physical examination revealed no cardiopulmonary compromise. Anesthesia was induced while an assistant immobilized the cervical spine and an atraumatic intubation was performed. Surgery was uneventful. Muscle paralysis was reversed, demonstrated by normalization of the train-of-four response, and the patient was extubated awake. Shortly postextubation, the patient developed inspiratory stridor, which disappeared after a second dose of neostigmine. The patient was transported to the postanesthesia care unit. Just prior to arrival the patient once again developed inspiratory stridor, became distressed, and oxygen saturation decreased. Direct laryngoscopy followed by a nasal fibreoptic examination of the larynx was performed. Cricoarytenoid arthritis secondary to rheumatoid arthritis with airway compromise was diagnosed. An uneventful awake tracheostomy was performed. The patient was discharged on day ten with a colostomy and a tracheostomy in place. One month postdischarge the patient's trachea was decannulated. On follow-up, a normal voice and mobile cords were observed. CONCLUSION: Cricoarytenoid arthritis is an infrequent complication of rheumatoid arthritis. A thorough history and physical examination are necessary to recognize signs and symptoms of cricoarytenoid arthritis. Prompt recognition of airway obstruction due to cricoarytenoid arthritis is essential for appropriate management. | |
15338491 | Risk factors for methotrexate-induced abnormal laboratory monitoring results in patients w | 2004 Sep | OBJECTIVE: To determine risk factors for methotrexate (MTX)-induced hepatic and hematologic laboratory abnormalities in patients with rheumatoid arthritis (RA). METHODS: Measurements of aspartate aminotransferase (AST), white blood cell counts, and platelet counts were collected in a database of patients with RA receiving MTX from 1991 through 2002. Potential risk factors for toxicity were recorded on each patient. RESULTS: Four hundred and eighty-one patients were followed for 2,323 person-years of MTX exposure. MTX was discontinued permanently because of abnormal laboratory test results in 22 patients (4.6%), the majority of whom (17/22, 77%) had elevated AST values. The body mass index (BMI) was significantly higher in those patients where MTX was permanently discontinued than in those in whom it was not (p < 0.03). Independent predictors of a significantly higher percentage of abnormal AST values were lack of folate supplementation (p < 0.001) and untreated hyperlipidemia (p < 0.02). Of the 17 patients in whom MTX was discontinued permanently because of an elevated AST value, 11/17 (65%) had either lack of folate supplementation or untreated hyperlipidemia. Hypoalbuminemia correlated independently with an increased percentage of abnormal platelet counts (p < 0.03). CONCLUSION: Lack of folate supplementation, untreated hyperlipidemia, and elevated BMI identified patients receiving MTX at risk for transaminase elevation, and low serum albumin was a risk factor for thrombocytopenia. Nonalcoholic fatty liver disease could be the underlying risk factor for transaminase elevation in patients with hyperlipidemia and obesity. | |
14505211 | A comparison of bone loss in early and late rheumatoid arthritis using quantitative phalan | 2003 Sep | This study compares amplitude-dependent speed of sound (AD-SoS) measured by phalangeal ultrasonography in a group of 60 patients with early rheumatoid arthritis (RA) with those who had had the disease for more than 4 years. The mean duration of the early disease group was 1.4 years, and the mean of the established RA group was 14.6 years. Plasma viscosity (PV), C-reactive protein (CRP) and HAQ scores were obtained. Forty-nine patients with early RA had hand radiographs assessed by the Larsen score method. The DBM Sonic system was assessed on normal volunteers and a coefficient of variation of 0.88% obtained. A significant correlation was found between the left and right hands of the patients groups studied ( r=0.84). The mean Z score of both hands was therefore used in comparing the two clinical groups. Results showed no correlation between CRP, PV and Z scores of AD-SoS. The HAQ scores showed a weak negative correlation, and there was no correlation between the Larsen score and Z score, or the number of swollen joints and Z score. However, the early and established groups with RA were significantly different (#E5/E5#=0.004). Within the early RA group the Z score for AD-SoS was lower in those with disease duration of less than 2 years (-1.71) than in those with disease duration of 2-4 years (-1.01). This suggests that bone loss in the fingers is greater in the first 2 years of disease than in the following 2 years, which might reflect an effect of treatment. | |
12209031 | Increased levels of autoantibodies against copper-oxidized low density lipoprotein, malond | 2002 Sep | OBJECTIVES: To analyse the association of autoantibodies against cardiolipin (CL) and oxidized low density lipoproteins [copper-oxidized low density lipoprotein (oxLDL), malondialdehyde-modified LDL (MDA-LDL)] with rheumatoid arthritis (RA) and cardiovascular complications. METHODS: One hundred and twenty-one patients with RA were consecutively included. Autoantibodies were determined by ELISA. Healthy individuals from the same region were used as controls. RESULTS: Levels of IgG, IgM and IgA antibodies against MDA-LDL and CL, as well as IgG and IgA antibodies against oxLDL were increased in the patients (P<0.01). The prevalence of IgG, IgM and IgA antibodies against CL was higher than in the normal population (74, 82 and 14%, respectively). The prevalence of IgG and IgA antibodies against oxLDL was also significantly increased (35 and 25%, respectively) and so was the prevalence of IgG and IgM antibodies against MDA-LDL (17 and 26%, respectively) compared with controls. The levels of IgM and IgA antibodies against aCL and IgM against MDA-LDL were increased in patients with extra-articular manifestations. Patients who developed myocardial infarction had a higher prevalence of IgG antibodies against MDA-LDL (P=0.04). There were substantial correlations between the levels of antibodies against oxLDL, MDA-LDL and CL. CONCLUSIONS: RA patients had increased levels and prevalence of autoantibodies against CL, oxLDL and MDA-LDL, with associations to severity of disease and cardiovascular complications. | |
12124859 | A subset of natural killer cells is greatly expanded within inflamed joints. | 2002 Jul | OBJECTIVE: To determine whether natural killer (NK) cells are present within inflamed joints and whether they might play a role in amplifying the inflammatory process. METHODS: Paired samples of peripheral blood and synovial fluid were obtained from 22 patients with inflammatory arthritis. The frequency and phenotype of the peripheral and synovial NK cells were analyzed using a panel of monoclonal antibodies. Further experiments were performed to investigate the functional capacity of the synovial NK cells. RESULTS: The study showed that the CD3-, CD56(bright) subset of NK cells was greatly expanded within inflamed joints. Our experiments suggested that this subset of cells was preferentially recruited from the periphery and that NK cells may be further activated by cytokines present within the joint. Furthermore, synovial NK cells responded to a combination of interleukin-12 (IL-12) and IL-15, cytokines that are secreted by cells of the monocyte/macrophage lineage, by rapidly secreting interferon-gamma, a cytokine that can, in turn, activate macrophages. CONCLUSION: A subset of NK cells was expanded within inflamed joints. The functional properties of these NK cells rendered them good candidates for a role in interacting with the macrophage/monocyte population within the joint, thus amplifying the production of proinflammatory cytokines. |