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ID PMID Title PublicationDate abstract
16541097 Negative association between the chemokine receptor CCR5-Delta32 polymorphism and rheumato 2006 Apr Rheumatoid arthritis (RA) is characterized by synovial inflammation mediated by T-cells, monocytes and macrophages. The homing of these cells to the inflamed synovium is regulated by chemokine-receptors and their ligands. A 32-basepair deletion (Delta32) in the gene encoding CCR5, a chemokine-receptor, results in a non-functional receptor. A negative association between CCR5-Delta32 and RA has been described, although other studies found no associations. Furthermore, the observation that individuals homozygous for CCR5-Delta32 develop RA has raised questions about the role of CCR5-Delta32. This meta-analysis of all published case-control association studies confirms the negative association between CCR5-Delta32 and RA (Odds Ratio=0.65; 95% confidence intervals=0.55-0.77; P<0.0001), suggesting that CCR5-Delta32 is protective against the development of RA. CCR5 blockade in animal models of RA results in amelioration of arthritis, suggesting that CCR5 blockade could also modify disease in patients with RA.
17394217 Work disability among two cohorts of women with recent-onset rheumatoid arthritis: a survi 2007 Apr 15 OBJECTIVE: To analyze factors associated with leaving employment among women with newly diagnosed rheumatoid arthritis (RA). METHODS: Women with RA were recruited from a national sample of rheumatologists in 1987 and 1998. Inclusion criteria were RA diagnosis <18 months earlier, age >or=18 years, and no other disabling health condition. The 1987 and 1998 cohorts comprised 48 and 91 women, respectively. Data were collected by telephone for 4 years. Survival analysis was conducted using Kaplan-Meier curves and a proportional hazards generalized linear model to assess whether the time to stopping work differed between the cohorts and to identify baseline predictors and time-varying covariates of leaving work. RESULTS: Most patients were age <50 years, married, had >12 years of education, and were white. Fifteen patients (31%) in the 1987 cohort and 24 patients (26%) in the 1998 cohort stopped working in the observation periods. Kaplan-Meier survival curves for each cohort were not significantly different. Multivariate analyses demonstrated that married women (P = 0.03) and those with joint deformities (P = 0.00) were more likely to stop working. A significant flares by cohort interaction (P = 0.01) indicated that, in comparison with patients in the 1998 cohort, those in the 1987 cohort with <2 disease flares had the lowest risk of stopping work and those with >or=2 flares had the greatest risk. CONCLUSION: Unexpectedly, the cumulative rate of stopping work among women in the 1998 study did not differ from that among women diagnosed >16 years earlier. However, disease flares greatly affected employment in the 1987 but not the 1998 cohort, possibly indicating that newer medications were effective in maintaining functional status among those with more severe disease activity, measured by number of flares, in the 1998 group.
17080534 The effectiveness of RA wrist fusion using Beta-TCP without autogenous iliac bone grafting 2006 Wrist arthrodesis is indicated for the rheumatoid hand especially in cases with severe destruction of the carpal bones. In the arthrodesis procedure for the rheumatoid wrist, autogenous iliac bone grafting is required in most cases. However, autogenous iliac bone graft necessitates the additional surgical intervention, and can be associated with the problem of inadequate bony quality or quantity. It is thought that use of the artificial bone substitute in the procedure can lessen the surgical morbidity while supplying the consistent material without shortage of graft quantity. We have performed arthrodesis of the rheumatoid wrist using beta-TCP for four patients. Clinical results of these patients were satisfactory both in pain relief and functional improvement with complete bony healing. Therefore, this procedure seems to be an effective option for the rheumatoid wrist with severe destructive changes.
18021334 Population pharmacokinetic investigation of low-dose methotrexate in rheumatoid arthritics 2007 Dec OBJECTIVE: To estimate the population pharmacokinetics of low-dose methotrexate (MTX) in Japanese patients using nonmem, a computer program designed for analysing drug pharmacokinetics in study populations through pooling of data. METHOD: A total of 153 serum concentration measurements obtained from the 17 healthy volunteers and 17 patients with rheumatoid arthritis were collected. Analysis of the pharmacokinetics of MTX was accomplished using a two-compartment pharmacokinetic model with first-order absorption. The effect of a variety of developmental and demographic factors on MTX disposition was investigated. RESULTS: The final pharmacokinetic parameters were CL/F (L/kg/h) = 0.177 x 0.394MULT, V1/F (L/kg) = 0.0501, Q/F (L/kg/h) = 0.056, V2/F (L/kg) = 0.368, ka (h-1) = 0.503, where CL is total body clearance, V1 and V2 is apparent volume of distribution in the central and peripheral compartments, k(a) is absorption rate constant, Q is intercompartmental clearance and MULT = 1 for patients received multiple dosing and zero otherwise. The interindividual variabilities in CL, Q and V1 were 25.7%, 22.3% and 217.9%, respectively, and the residual variability was 17.8% as a coefficient of variation. Because of the lake of information on data set we were unable to characterize the interindividual variability for V2 and ka. CONCLUSION: Clinical application of the model to patient care may permit selection of an appropriate dosage to achieve target MTX concentrations, thus enabling the clinician to achieve the desired therapeutic effect in Japanese patients. However, the MTX dosage regimen for the individual patient should be based on a careful appraisal of their clinical need for the drug.
16482644 Prevalence and associated factors for falls in women with established inflammatory polyart 2006 Apr OBJECTIVE: To determine the one-year period prevalence and factors associated with falls in a community based cohort of women with established inflammatory polyarthritis (IP). METHODS: The Norfolk Arthritis Register is a primary-care based inception cohort of subjects with IP aged 16 years and over. At the 10-year visit, subjects completed the Health Assessment Questionnaire (HAQ) and were examined for both active and inactive joint involvement. A subset of subjects was invited to complete a questionnaire about falls in the previous 12 months and questions about putative risk factors for falls. Logistic regression was used to determine whether there was any association between falls in the previous year and both putative disease and non-disease related risk factors. RESULTS: Of the 316 women (mean age 59 yrs) who completed the falls questionnaire, 34% reported a fall in the previous year. Falls were more frequent in those over age 75 years, although there was no significant linear increase in risk with age. Swollen joint count [per 10 joints, odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8] and increasing visual analog scale pain score (per 10 mm, OR 1.1; 95% CI 1.0, 1.2) were associated with an increased risk of falls. Those who fell had higher overall HAQ scores (OR 1.7; 95% CI 1.3, 2.3) as well as higher scores for all of the individual domains of the HAQ (OR 1.7 to 2.2). Similarly, low levels of outdoor physical activity (OR 3.3; 95% CI 1.7, 6.5), impaired vision (OR 2.7; 95% CI 1.2, 6.3), and impaired general health (OR 2.9; 95% CI 1.7, 4.8) were associated with an increased risk of falls. In a multivariate model, HAQ score, low levels of physical activity, impaired vision, and impaired general health were independently linked with falls. Sixty-one percent of subjects with 3 of these risk factors had reported a fall in the previous year. CONCLUSION: In this inception cohort of women with longstanding IP, one in 3 reported falling in the previous year. Using a simple measure, a group that had particularly high risk can be identified.
17530704 Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in e 2007 Jun OBJECTIVE: To assess the association between the initiation of anti-tumor necrosis factor alpha (anti-TNFalpha) therapy and the risk of serious bacterial infections in routine care. METHODS: This was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease-modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti-TNFalpha therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization. RESULTS: The incidence of serious bacterial infections was, on average, 2.2 per 100 patient-years in this population (95% confidence interval [95% CI] 2.0-2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5-3.1]), with a clear dose-response relationship for dosages >5 mg/day (for < or = 5 mg/day, RR 1.34; for 6-9 mg/day, RR 1.53; for 10-19 mg/day, RR 2.97; and for > or = 20 mg/day, RR 5.48 [P for trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti-TNFalpha therapy (RR 1.0 [95% CI 0.6-1.7]) or other DMARDs as compared with initiators of MTX. CONCLUSION: In a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti-TNFalpha therapy compared with users of MTX. Glucocorticoid use was associated with a dose-dependent increase in such infections.
17196579 Increased DNA damage and oxidative stress in patients with rheumatoid arthritis. 2007 Feb OBJECTIVES: Oxidative stress has been described as an important mechanism that underlies chronic inflammation in rheumatoid arthritis (RA). The aim of the study was to investigate the peripheral DNA damage, total antioxidant status (TAS), and total oxidative status (TOS) in patients with RA. DESIGN AND METHODS: The study population contained 25 patients with RA and 26 healthy controls. DNA damage was assessed by alkaline comet assay in peripheral lymphocyte, plasma levels of total antioxidant status (TAS) and total oxidative status (TOS) were determined, and OSI was calculated using a novel automated measurement method. Disease activity was evaluated by DAS-28 score. RESULTS: In RA patients, DNA damage was significantly higher than in controls (20.0+/-9.6 AU, 7.6+/-4.3 AU; p<0.001). Plasma TOS and OSI were higher in patients than in healthy controls (9.9+/-2.6 vs. 7.3+/-1.1, p<0.001; 1.04+/-0.4 vs. 0.7+/-0.1, p<0.001, respectively). Plasma TAS level in patients was lower than in healthy controls (0.9+/-0.7 vs. 1.01+/-0.7, p<0.001). DNA damage was correlated with TOS, OSI, and DAS-28 scores (r=0.682, p<0.001; r=0.753, p<0.001; r=0.519, p=0.008, respectively). CONCLUSIONS: The findings indicated that lymphocyte DNA damage level increases in patients with RA. Elevated DNA damage may be related with increased oxidative stress and decreased antioxidant capacity. However, the mechanism of this association, and whether it is direct or indirect, remains to be explored.
16735488 Evidence for the role of small ubiquitin-like modifier 4 as a general autoimmunity locus i 2006 Aug CONTEXT: Recently, an association of a single nucleotide polymorphism, 163A>G encoding M55V, in the gene SUMO4, which has been shown to be a negative feedback regulator for nuclear factor kappaB, has been reported in type 1 diabetes. OBJECTIVE: To establish whether SUMO4 locus contributes to the genetic susceptibility to other autoimmune disorders, a case-control analysis was carried out using genomic DNA from type 1 diabetes, autoimmune thyroid disease (AITD), rheumatoid arthritis (RA), and primary Sjögren's syndrome. SUBJECTS: A total of 1480 samples, including 929 cases (411 patients with type 1 diabetes, 292 AITD, 172 RA, and 54 primary Sjögren's syndrome) and 551 healthy control subjects of Japanese origin participated in the study. METHODS: The 163A>G (rs237025, M55V) polymorphism of SUMO4 was genotyped. RESULTS: SUMO4 M55V variant was associated not only with type 1 diabetes [odds ratio (OR), 1.42; 95% confidence interval (CI), 1.09-1.84; P = 0.0072], but also with increased risk of other autoimmune diseases, AITD (OR, 1.52; 95% CI, 1.14-2.03; P = 0.0041) and RA without amyloidosis (OR, 1.53; 95% CI, 1.65-2.24; P = 0.027), but not primary Sjögren's syndrome. Furthermore, the association of SUMO4 M55V variant was stronger in type 1 diabetic patients complicated with AITD (OR, 1.62; 95% CI, 1.06-2.47; P = 0.023) and in patients who have neither type 1 diabetes-susceptible class II HLA, DRB1*0405 nor DRB1*0901 (OR, 2.28; 95% CI, 1.34-3.87; P = 0.0018). CONCLUSIONS: These results indicate that the SUMO4 is a more common autoimmune disease gene and a supplementary risk factor to type 1 diabetes in conjunction with class II HLA.
18311768 Five-year followup of a cognitive-behavioral intervention for patients with recently-diagn 2008 Mar 15 OBJECTIVE: To investigate whether cognitive-behavioral therapy (CBT) administered early in the course of rheumatoid arthritis (RA) has long-term effects on health care use. METHODS: We reviewed the files of 47 of the original 53 patients with early RA who volunteered for a randomized controlled trial comparing CBT with no psychological intervention. Occasions of service provision associated with RA were documented and health care use was compared between groups. RESULTS: The CBT group used fewer health care resources than the control group in the 5 years following intervention. Significant differences were observed for the number of inpatient nights, physiotherapy referrals, injections, and for total health care use. There was a trend that closely approached significance toward fewer episodes of surgery and orthopedic referrals in the CBT group. CONCLUSION: These results suggest that CBT administered early in the course of RA can reduce health care use for the first 5 years after treatment. This is a stringent test of the efficacy of a brief psychological intervention, and supports the fact that brief psychological treatments can have long-term effects.
18163406 Missing data in randomized controlled trials of rheumatoid arthritis with radiographic out 2008 Jan 15 OBJECTIVE: To assess the impact, in terms of statistical power and bias of treatment effect, of approaches to dealing with missing data in randomized controlled trials of rheumatoid arthritis with radiographic outcomes. METHODS: We performed a simulation study. The missingness mechanisms we investigated copied the process of withdrawal from trials due to lack of efficacy. We compared 3 methods of managing missing data: all available data (case-complete), last observation carried forward (LOCF), and multiple imputation. Data were then analyzed by classic t-test (comparing the mean absolute change between baseline and final visit) or F test (estimation of treatment effect with repeated measurements by a linear mixed-effects model). RESULTS: With a missing data rate close to 15%, the treatment effect was underestimated by 18% as estimated by a linear mixed-effects model with a multiple imputation approach to missing data. This bias was lower than that obtained with the case-complete approach (-25%) or LOCF approach (-35%). This statistical approach (combination of multiple imputation and mixed-effects analysis) was moreover associated with a power of 70% (for a 90% nominal level), whereas LOCF was associated with a power of 55% and a case-complete power of 58%. Analysis with the t-test gave qualitatively equivalent but poorer quality results, except when multiple imputation was applied. CONCLUSION: Our simulation study demonstrated multiple imputation, offering the smallest bias in treatment effect and the highest power. These results can help in planning trials, especially in choosing methods of imputation and data analysis.
18575424 Neurological disorders with demyelinating brain white matter lesions in a patient with rhe 2008 Apr We present the case of a 37-year-old woman with severe, drug-resistant rheumatoid arthritis. The patient has been previously treated with several disease-modifying anti-rheumatic drugs as well as infliximab alone and in combination therapy. Despite the treatment, a high disease activity persisted. For this reason, the patient was qualified to etanercept therapy. During the therapy, a gradual joint condition improvement was demonstrated, including arthritis remission. From the fourth month of etanercept administration, neurological disorders such as sight and speech disorders, amentia and muscle weakening were reported. The symptoms aggrevated with therapy continuation. The patient reported her complaints to her leading rheumatologist after 8 months of their duration. Optic fundus and visual area examination, as well as in the neurological examination no significant abnormalities were found. Magnetic resonance imaging of the head demonstrated single, small hyperintensive lesions in the T2w images located in the white matter of the frontal and parietal lobes of the left cerebral hemisphere, which could be identical with demyelization. Based on the clinical and laboratory findings, drug-induced neurological disorders associated with etanercept administration were suspected. After discontinuation of etanercept therapy, the complaints gradually subsided. The amentia episodes, concentration disorders and speech disorders were less frequent. There was no relapse of muscle weakening. Within 6 months of the drug discontinuation, neurological symptoms resolved completely.
17661050 Etanercept reduces the oxidative stress marker levels in patients with rheumatoid arthriti 2008 Jan This study was performed to evaluate the effects of the TNF-alpha inhibitor etanercept on oxidation stress markers representing DNA damage, lipid peroxidation, and protein glycosylation. Twenty-two rheumatoid arthritis (RA) patients underwent etanercept treatment. The levels of serum total, urinary total, and urinary free pentosidine, which is an advanced glycation end-product (AGE), of urinary N(epsilon)-hexanoyl lysine (N(epsilon)-HEL), and of 8-hydroxy-deoxy guanosine (8-OHdG) were measured at baseline and at 3 and 6 months after the initial treatment with etanercept. Serum total and urinary total pentosidine levels were reduced at 6 months after the initial treatment with etanercept, and urinary free pentosidine levels were reduced at 3 and 6 months. Urinary N(epsilon)-HEL levels were also reduced at 3 and 6 months, and urinary 8-OHdG levels were reduced at 6 months. Serum total and urinary total pentosidine levels in RA patients correlated with the number of swelling joints and tender joints, and urinary total pentosidine levels correlated with the Disease Activity Score using 28 joints (DAS28). This study demonstrated that etanercept acts as a regulator against pentosidine formation, oxidative DNA damage, and lipid peroxidation in RA patients.
18209094 Successful treatment of animal models of rheumatoid arthritis with small-molecule cyclin-d 2008 Feb 1 Intraarticular gene transfer of cyclin-dependent kinase (CDK) inhibitors to suppress synovial cell cycling has shown efficacy in treating animal models of rheumatoid arthritis. Endogenous CDK inhibitors also modulate immune function via a CDK-independent pathway. Accordingly, systemic administration of small molecules that inhibit CDK may or may not ameliorate arthritis. To address this issue, alvocidib (flavopiridol), known to be tolerated clinically for treating cancers, and a newly synthesized CDK4/6-selective inhibitor were tested for antiarthritic effects. In vitro, they inhibited proliferation of human and mouse synovial fibroblasts without inducing apoptosis. In vivo, treatment of collagen-induced arthritis mice with alvocidib suppressed synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII were maintained. Treatment was effective even when therapeutically administered. Treated mice developed arthritis after termination of treatment. Thus, immune responses to CII were unimpaired. The same treatment ameliorated arthritis induced by K/BxN serum transfer to lymphocyte-deficient mice. Similarly, the CDK4/6-selective inhibitor suppressed collagen-induced arthritis. Both small-molecule CDK inhibitors were effective in treating animal models of rheumatoid arthritis not by suppressing lymphocyte function. Thus, the two small-molecule CDK inhibitors ameliorated arthritis models in a distinctive way, compared with other immunosuppressive drugs.
18174217 Tumour necrosis factor blockade increases lymphangiogenesis in murine and human arthritic 2008 Nov OBJECTIVE: To investigate the presence and regulation of lymphatic vessels in inflamed joints of mice with experimental arthritis as well as patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Lymphatic vessels and blood vessels were assessed in synovial tissue of human tumour necrosis factor transgenic (TNFtg) mice and synovial biopsies from patients with RA and SpA by immunohistochemistry for podoplanin and CD31, respectively. Assessments were performed before and after TNF blockade in all biopsies. RESULTS: Lymphatic vessels were abundantly present in the synovial tissue of hTNFtg mice as well as patients with RA and SpA. The number of lymphatic vessels was positively related to the severity of synovial inflammation. Treatment with infliximab led to an increase in the formation of lymphatic vessels in murine and human inflammatory tissue. CONCLUSIONS: This study shows that TNF blockade promotes the proliferation of lymphatic vessels in the inflamed synovium of RA and SpA. This finding leads to the assumption that promotion of lymphangiogenesis may play an important part in efflux of cells and fluid out of the inflamed tissue.
16475897 Diagnosis and prognosis of early rheumatoid arthritis, with special emphasis on laboratory 2006 Diagnosis of rheumatoid arthritis (RA) is mainly based on clinical criteria of symmetric polyarthritis of the hands and feet, with morning stiffness lasting usually more than 1 h. Autoantibodies typical for RA, i.e., rheumatoid factors and anti-cyclic citrullinated peptide, and measurements of inflammation add more specific information, especially for early diagnosis, where clinical presentation may be oligosymptomatic involving only a few joints. These laboratory parameters are also relevant for prognosis of disease persistence, functional impairment and radiological progression.
17233401 [A case of HLA-B54 positive silicosis with rheumatoid arthritis and lung cancer]. 2006 Dec In the same environment or workplace, some people contract pneumoconiosis, including silicosis, and some do not. This suggests the important role of constitutional predisposition. In Japanese cases with silicosis, the frequency of HLA-B54 was increased and disease susceptibility gene (s) may exist near the HLA-B locus. It is well known that silicosis is frequently accompanied with rheumatoid arthritis, probably due to the effects of silica on the immunological system. We encountered a case of silicosis with rheumatoid arthritis and lung cancer, who was found to have HLA-B54.
16519794 Enhanced expression of mRNA for nuclear factor kappaB1 (p50) in CD34+ cells of the bone ma 2006 Bone marrow CD34+ cells from rheumatoid arthritis (RA) patients have abnormal capacities to respond to tumor necrosis factor (TNF)-alpha and to differentiate into fibroblast-like cells producing matrix metalloproteinase (MMP)-1. We explored the expression of mRNA for nuclear factor (NF)kappaB in RA bone marrow CD34+ cells to delineate the mechanism for their abnormal responses to TNF-alpha. CD34+ cells were purified from bone marrow samples obtained from 49 RA patients and 31 osteoarthritis (OA) patients during joint operations via aspiration from the iliac crest. The mRNAs for NFkappaB1 (p50), NFkappaB2 (p52) and RelA (p65) were examined by quantitative RT-PCR. The expression of NFkappaB1 mRNA in bone marrow CD34+ cells was significantly higher in RA than in OA, whereas there was no significant difference in the expression of mRNA for NFkappaB2 and RelA. The expression of NFkappaB1 mRNA was not correlated with serum C-reactive protein or with the treatment with methotrexate or oral steroid. Silencing of NFkappaB1 by small interfering RNA abrogated the capacity of RA bone marrow CD34+ cells to differentiate into fibroblast-like cells and to produce MMP-1 and vascular endothelial growth factor upon stimulation with stem cell factor, granulocyte-macrophage colony stimulating factor and TNF-alpha without influencing their viability and capacity to produce beta2-microglobulin. These results indicate that the enhanced expression of NFkappaB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-alpha and, thus, in the pathogenesis of RA.
18240230 Stress activation of cellular markers of inflammation in rheumatoid arthritis: protective 2008 Feb OBJECTIVE: Psychological stress is thought to aggravate disease activity in rheumatoid arthritis (RA), although the physiologic mechanisms are unclear. Tumor necrosis factor alpha (TNFalpha) is an inflammatory cytokine involved in the exacerbation of RA, and TNFalpha antagonists have emerged as efficacious treatments. The purpose of this study was to determine whether RA patients show increased monocyte production of TNFalpha following acute psychological stress and whether such responses are abrogated in RA patients taking TNFalpha antagonists. METHODS: A standardized stress task was administered to 3 groups of subjects: RA patients taking TNFalpha antagonists, RA patients not taking such medications, and healthy controls. Lipopolysaccharide-stimulated monocyte production of inflammatory cytokines was repeatedly measured using intracellular staining and flow cytometry. Subjective stress, cardiovascular responses, adrenocorticotropic hormone (ACTH) levels, and cortisol levels were also measured. RESULTS: The stress task induced increases in subjective stress, cardiovascular activity, and levels of ACTH and cortisol, with similar responses in the 3 groups. In addition, the stress task induced a significant increase (P < 0.001) in monocyte production of TNFalpha among RA patients who were not taking TNFalpha antagonists. However, monocyte production of TNFalpha did not change following psychological stress in RA patients taking TNFalpha antagonists or in healthy controls. CONCLUSION: Brief psychological stress can trigger increased stimulated monocyte production of TNFalpha in RA patients. The use of TNFalpha antagonists protects against stress activation of cellular markers of inflammation in RA patients.
18991285 Arthritogenic dsRNA is present in synovial fluid from rheumatoid arthritis patients with a 2008 Nov Viruses may be part of the pathogenesis of rheumatoid arthritis (RA). Double stranded RNA (dsRNA) is a prototypic viral conformation of nucleic acid that is highly arthritogenic in mice. Therefore, we developed an ELISA to detect dsRNA in sera and synovial fluids (SF) in RA patients and in osteoarthritic controls. The developed ELISA recognizes picogram levels of viral or synthetic dsRNA but shows no reactivity against DNA, synthetic ssRNA, or total RNA prepared from mammalian cells. Before analysis by ELISA, each sample was subjected to RNA precipitation. The RA patients had significantly higher levels of dsRNA than the osteoarthritis patients in SF and in sera. In 7 of 17 RA patients, EBV was present in SF and in all but one of these this was accompanied by the presence of dsRNA. No parvovirus, cytomegalovirus, or polyomavirus was detected. The anti-viral cytokine IFN-alpha was detected in SF in 10 of 21 RA patients, but in none of the osteoarthritis patients. Notably, RA patients with erosive disease course had significantly higher levels of dsRNA in SF than non-erosive patients, but no correlation between dsRNA levels and the presence of RF or levels of C-reactive protein, IL-6, or IFN-alpha was observed.
17127417 The role of B cells in animal models of rheumatoid arthritis. 2007 Jan 1 Rheumatoid arthritis is a chronic systemic inflammatory autoimmune disease that affects approximately 1% of the population. Recent studies demonstrate a significant improvement in clinical symptoms in patients treated with Rituximab, an anti-CD20 monoclonal antibody that depletes pro-B cells and mature B cells but not plasma cells. These findings indicate that B cells are an important contributor to the pathogenesis of RA. In this review we will examine the role of B cells in several different murine models of RA. There are a number of antibody-dependent mechanisms by which B cells support inflammatory processes in the joint. However, there are also antibody-independent mechanisms that involve B cell/T cell collaboration where B cells may modulate autoreactive T cell responses. In addition, B cells may be an important source of cytokines that either stimulate or inhibit autoimmune responses. Understanding the role of B cells in RA will provide new and directed therapeutic approaches to the treatment of disease.