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ID PMID Title PublicationDate abstract
19723897 What factors influence the health status of patients with rheumatoid arthritis measured by 2009 Oct OBJECTIVE: The Health Assessment Questionnaire Disability Index (HAQ) is a widely used outcome measure in rheumatoid arthritis (RA), whereas the SF-12v2 Health Survey (SF-12) was introduced recently. We investigated how the HAQ and SF-12 were associated with socio-demographic, lifestyle, and disease- and treatment-related factors in patients with RA. METHODS: In RA patients from 11 Danish centers, clinical and patient-reported data, including the HAQ and SF-12, were collected. Three multiple linear regression models were estimated, with the HAQ, SF-12 physical component score (PCS), and SF-12 mental component score (MCS) as outcome and sociodemographic, lifestyle, and RA-related treatment and comorbidity characteristics as explanatory variables. RESULTS: In total, 3156 (85%) of 3704 invited patients participated--75% women, 76% rheumatoid factor-positive, median age 61 years (range 15-93 yrs), disease duration 7 years (range 0-68 yrs), Disease Activity Score on 28 joints (DAS28) 2.97 (range 0.96-8.61), HAQ score 0.63 (range 0-3), SF-12 PCS 56 (range 6-99), and SF-12 MCS 57 (range 16-99). Variation in HAQ was associated with 12 of 15 possible variables (R(2) 0.41), in PCS and MCS with 6 of 15 variables (R(2) 0.02 and 0.05). Patients with moderate to high DAS28 and > or = 3 comorbid conditions had consistently worse HAQ and SF-12 scores compared to the reference groups, while weekly exercise was associated with better scores compared to no exercise. CONCLUSION: The HAQ was more sensitive to differences in demographic, lifestyle, and disease- and treatment-related factors than the SF-12. The established clinical value and feasibility of the HAQ highlights its advantages over the SF-12 in describing health status in RA.
19740903 Hormonal replacement therapy may reduce the risk for RA in women with early arthritis who 2010 Sep OBJECTIVE: To assess the effect of reproductive factors, especially hormone replacement therapy (HRT) and its interaction with HLA-DRB1 *01 and/or *04 alleles on the diagnosis of rheumatoid arthritis (RA) and the presence of anti-cyclic citrullinated peptide (CCP) antibodies in women included in the ESPOIR cohort (early arthritis cohort). METHODS: 568 patients were included in the analyses, which were performed using logistic regression. RESULTS: HRT reduced the risk of RA due to the HLA-DRB1 *01 and/or *04 alleles from OR 1.88 (95% CI 1.32 to 2.68, p<0.000) for HLA-DRB1 *01 and/or *04 alleles alone to OR 1.07 (95% CI 0.51 to 2.26, p=0.85) in women with HLA-DRB1 *01 and/or *04 alleles who received HRT. One explanation might be the protective effect of HRT on the presence of anti-CCP antibodies (OR 0.43, 95% CI 0.24 to 0.77, p<0.006). Other reproductive factors such as the number of pregnancies, menopause and age at menopause, age at menarche and a history of pregnancy with poor outcome were not associated with the diagnosis of RA and the presence of anti-CCP antibodies. CONCLUSION: HRT may reduce the risk of RA due to HLA-DRB1 *01 and/or *04 alleles by protecting against the production of anti-CCP antibodies.
20231210 Health literacy predicts the discrepancy between patient and provider global assessments o 2010 May OBJECTIVE: Numerous studies report that significant discordance exists between patient and provider [physician] measures of rheumatoid arthritis (RA). We examined whether health literacy explains this discordance. METHODS: We recruited English-speaking adult patients with RA for this cross-sectional study. Subjects completed 2 versions of patient global assessments of disease activity (PTGA), using standard terminology from the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) and the 28-joint count Disease Activity Score 28 (DAS28). The provider global assessment (MDGA) was also obtained. The discrepancy between PTGA and MDGA was calculated as the absolute difference between these assessments. We used validated instruments [Short Test of Functional Health Literacy in Adults (S-TOFHLA) and Rapid Estimate of Adult Literacy in Medicine (REALM)] and linear regression to determine whether health literacy predicts disease measure discrepancy. RESULTS: The study included 110 subjects. Limited health literacy was a common finding by both the REALM and S-TOFHLA. PTGA and MDGA showed fair to good correlation (r = 0.66-0.68), although both versions of the PTGA were significantly higher than MDGA by the t-test (p < 0.001). The S-TOFHLA and REALM both were associated with the absolute difference between the MDGA and PTGA by linear regression, and results remained statistically significant in multivariate analysis. CONCLUSION: Health literacy was independently associated with the extent of discrepancy between PTGA and MDGA in English-speaking patients with RA at an urban clinic. This finding should influence our interpretation of disease measures.
19485909 Potential effect of anti-tumour necrosis factor-alpha treatment on reducing the cardiovasc 2010 Mar Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects about 1% of the adult population. RA sufferers not only have a high chronic disease burden, but may also experience increased cardiovascular disease (CVD) and mortality as the prevalence of myocardial infarction (MI) is 4 times higher in RA patients than in general population, and there is ample evidence showing that coagulation processes are active in RA. Fibrin accumulation in the synovium is one of the most striking pathological features of rheumatoid synovitis and characteristic RA antibodies such as anti-citrullinated protein antibodies (ACPA) can cross-react with epitopes exposed on fibrin and fibrinogen molecules, and thus impair fibrinolysis. The inflammation, coagulation and fibrinolytic systems are modulated by a common mechanism that includes the involvement of proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). It has long been recognised that extensive cross-talk takes place between the coagulation pathway and the inflammatory process at various levels, and there is growing evidence that this interaction may be relevant to arthritis. Large-scale, long-term studies have shown that anti-TNF-alpha treatment improves the clinical and laboratory measures of disease activity, and reduces local and systemic inflammation. TNF-alpha blockade may therefore also reduce the impaired coagulation and cardiovascular risk associated with RA. This review provides an overview of the pathophysiological role of TNF-alpha in thrombotic mechanisms and the evidence so far available indicating that anti-TNF-alpha treatment can modify cardiovascular risk in RA.
20727199 Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity 2010 INTRODUCTION: The glucocorticoid receptor (GR) plays an important regulatory role in the immune system. Four polymorphisms in the GR gene are associated with differences in glucocorticoid (GC) sensitivity; the minor alleles of the polymorphisms N363 S and BclI are associated with relative hypersensitivity to GCs, while those of the polymorphisms ER22/23EK and 9β are associated with relative GC resistance. Because differences in GC sensitivity may influence immune effector functions, we examined whether these polymorphisms are associated with the susceptibility to develop Rheumatoid Arthritis (RA) and RA disease severity. METHODS: The presence of GR polymorphisms was assessed in healthy controls (n = 5033), and in RA patients (n = 368). A second control group (n = 532) was used for confirmation of results. In RA patients, the relationship between GR polymorphisms and disease severity was examined. RESULTS: Carriers of the N363 S and BclI minor alleles had a lower risk of developing RA: odds ratio (OR) = 0.55 (95% confidence interval (CI) 0.32-0.96, P = 0.032) and OR = 0.73 (95% CI 0.58-0.91, P = 0.006), respectively. In contrast, 9β minor allele carriers had a higher risk of developing RA: OR = 1.26 (95% CI 1.00-1.60, P = 0.050). For ER22/23EK minor allele carriers a trend to an increased risk OR = 1.42 (95% CI 0.95-2.13, P = 0.086) was found. All ER22/23EK carriers (32/32) had erosive disease, while only 77% (259/336) of the non-carriers did (P = 0.008). In addition, ER22/23EK carriers were treated more frequently with anti-tumor necrosis factor-alpha (TNFα) therapy (P < 0.05). CONCLUSIONS: The minor alleles of the 9β and ER22/23EK polymorphisms seem to be associated with increased predisposition to develop RA. Conversely, the minor alleles of the N363 S and BclI polymorphisms are associated with reduced susceptibility to develop RA. These opposite associations suggest that constitutionally determined GC resistance may predispose to development of auto-immunity, at least in RA, and vice versa.
20143001 [Cardiac involvement in rheumatoid arthritis]. 2009 Oct Rheumatoid arthritis (RA) is a systemic disease of unknown etiology characterized by a chronic inflammatory process mainly leading to destruction of synovial membrane of small and major diarthrodial joints. The prevalence of RA within the general adult population is about 1% and female subjects in fertile age result mostly involved. It's an invalidating disease, associated with changes in life quality and a reduced life expectancy. Moreover, we can observe an increased mortality rate in this population early after the onset of the disease. The mortality excess can be partially due to infective, gastrointestinal, renal or pulmonary complications and malignancy (mainly lung cancer and non-Hodgkin lymphoma). Among extra-articular complications, cardiovascular (CV) involvement represents one of the leading causes of morbidity and mortality. Every cardiac structure can be affected by different pathogenic pathways: heart valves, conduction system, myocardium, endocardium, pericardium and coronary arteries. Consequently, different clinical manifestations can be detected, including: pericarditis, myocarditis, myocardial fibrosis, arrhythmias, alterations of conduction system, coronaropathies and ischemic cardiopathy, valvular disease, pulmonary hypertension and heart failure. Considering that early cardiac involvement negatively affects the prognosis, it is mandatory to identify high CV risk RA patients to better define long-term management of this population.
19228663 Hypoxia-induced abrogation of contact-dependent inhibition of rheumatoid arthritis synovia 2009 Apr OBJECTIVE: Uncontrolled proliferation of synovial fibroblasts is characteristic of the pathology of rheumatoid arthritis (RA). Since synovial tissues in the rheumatoid joints are hypoxic, we investigated how hypoxia affects RA synovial fibroblast (RASF) proliferation. METHODS: RASF were cultured at 2000 cells (low density culture) or at 5000 cells (high density, growth-inhibitory confluent culture) per microtiter well under hypoxic (10%, 3%, or 1% O2) or normoxic (21% O2) conditions. Some RASF were treated with recombinant human interleukin 1 receptor antagonist (IL-1ra), anti-tumor necrosis factor-alpha (TNF-alpha)-neutralizing antibodies, anti-N-cadherin-blocking antibodies, or MG132. 3H-labeled thymidine incorporation was quantified to assess their proliferation. Total RNA and cell lysates were prepared for real-time polymerase chain reaction and Western blot analyses. RESULTS: Hypoxia exerted no effect on proliferation of RASF cultured at low density. At high density, it abrogated contact-dependent growth inhibition of RASF, but not of human dermal fibroblasts. Addition of anti-TNF-alpha antibodies or IL-1ra did not affect the results. Upregulated expression of cyclin-dependent kinase inhibitor p27Kip1 was observed in the cells cultured at high density under normoxic conditions, but not under hypoxic conditions. Hypoxia decreased N-cadherin expression on RASF. Addition of anti-N-cadherin-blocking antibodies mimicked the effects of hypoxic culture; it promoted proliferation of RASF cultured at high density under normoxic conditions. This antibody treatment also downmodulated p27Kip1 expression. CONCLUSION: Hypoxia downregulates N-cadherin expression on RASF, and thus prevents p27Kip1 upregulation for their contact inhibition. It is likely that hypoxia in rheumatoid synovial tissues contributes to rheumatoid pathology by augmenting proliferation of synovial fibroblasts.
20096109 Regulation of IFN response gene activity during infliximab treatment in rheumatoid arthrit 2010 INTRODUCTION: Cross-regulation between TNF and type I IFN has been postulated to play an important role in autoimmune diseases. Therefore, we determined the effect of TNF blockade in rheumatoid arthritis (RA) on the type I IFN response gene activity in relation to clinical response. METHODS: Peripheral blood from 33 RA patients was collected in PAXgene tubes before and after the start of infliximab treatment. In a first group of 15 patients the baseline expression of type I IFN-regulated genes was determined using cDNA microarrays and compared to levels one month after treatment. The remaining 18 patients were studied as an independent group for validation using quantitative polymerase chain reaction (qPCR). RESULTS: Gene expression analysis revealed that anti-TNF antibody treatment induced a significant increase in type I IFN response gene activity in a subset of RA patients, whereas expression levels remained similar or were slightly decreased in others. The findings appear clinically relevant since patients with an increased IFN response gene activity after anti-TNF therapy had a poor clinical outcome. This association was confirmed and extended for an IFN response gene set consisting of OAS1, LGALS3BP, Mx2, OAS2 and SERPING1 in five EULAR good and five EULAR poor responders, by qPCR. CONCLUSIONS: Regulation of IFN response gene activity upon TNF blockade in RA is not as consistent as previously described, but varies between patients. The differential changes in IFN response gene activity appear relevant to the clinical outcome of TNF blockade in RA.
19208451 Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrul 2009 May BACKGROUND: Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFalpha antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy. METHODS: Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined. RESULTS: At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p<0.001), whereas anti-CCP showed little change (p=0.053). ANA titres increased significantly (p<0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16-3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16-4.13]). CONCLUSIONS: During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.
20732651 Prospects for gene therapy in inflammatory arthritis. 2010 Aug Gene therapy holds great promise for the treatment of rheumatoid arthritis (RA). In this article, we focus on innovation in vector, promoter or target genes. Gene therapy is defined as an introduction of nucleic acids into a host cell for therapeutic purposes; the option may be the overexpression of therapeutic gene or an underexpression of a target gene highly expressed in disease (small interfering RNA (siRNA)). The proof of principle in animal models of arthritis has shown convincingly that gene therapy can be an advantageous strategy in the treatment of RA. A gene therapy approach is advantageous over biologics for joint-specific targeting and long-term expression of an anti-arthritic molecule, replacing the frequent administration of recombinant proteins. We also discuss the currently used gene therapy clinical trials and define optimal strategies for success.
21196098 The lung in rheumatoid arthritis. 2011 Jan Rheumatoid arthritis (RA) is a common inflammatory disease, affecting about 1% of the population. Although a major portion of the disease burden including excess mortality is due to its extra-articular manifestations, the prevalence of RA-associated lung disease is increasing. RA can affect the lung parenchyma, airways, and the pleura; and pulmonary complications are directly responsible for 10 to 20% of all mortality. Even though pulmonary infection and drug toxicity are frequent complications of RA, lung disease directly associated with the underlying RA is more common. The prevalence of a particular complication varies based on the characteristics of the population studied, the definition of lung disease used, and the sensitivity of the clinical investigations employed. An overview of lung disease associated with RA is presented here with an emphasis on parenchymal lung disease, pleural effusion, and airway involvement.
19509326 Relative efficacies: antimalarials to abatacept - the choice is ours. 2009 Jun Early diagnosis and treatment of rheumatoid arthritis (RA) are important in order to halt disease progression and joint destruction, and minimize loss of function. Individually, the disease modifying antirheumatic drugs have demonstrated similar efficacies in radiological and clinical outcomes. However, various combination therapies have been shown to improve therapeutic outcomes for patients who fail to respond adequately to monotherapy. With the introduction of the cytokine inhibitors and the development of newer biologic therapies, a number of treatment options are available for patients with RA. The efficacies of the various treatment strategies are reviewed.
20868572 Anti-cyclic citrullinated peptides positivity rate in patients with familial Mediterranean 2010 Jul OBJECTIVES: To investigate the prevalence and levels of anti-cyclic citrullinated peptide antibodies (anti-CCP) in patients with familial Mediterranean fever (FMF) with and without arthritis. METHODS: Eighty-three patients with FMF and 43 healthy controls were included in the study. Thirty seven FMF patients had a history of arthritis, and 46 patients did not. Serum antibodies directed to the anti-CCP were assessed with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Values <20U were considered negative, between 20 and 39U low, 40-99U moderate, and >100U high positive. RESULTS: Positivity rate of anti-CCP in the whole FMF group (14.5%) was three-fold higher than the control group (4.7%). However, the difference failed to achieve a statistically significant level (p=0.09). Anti-CCP levels were 21±30.1 in patients with arthritis and 13.1±10.3 in the non arthritic group (p<0.05). Anti-CCP positivity rates were 10/37 (27%) in patients with arthritis and 2/46 (4.3%) in patients without arthritis (p<0.005). Five FMF patients with arthritis (13.5%) had moderate-high anti-CCP levels (>40U/ml). Anti-CCP levels were between 20-39U/ ml in 2FMF patients without arthritis and in 2 healthy controls. Anti-CCP positivity rate is higher in FMF patients with arthritis (27%) than healthy controls (4.7%) (p<0.005). CONCLUSIONS: Anti-CCP prevalence is higher in FMF patients with arthritis than without arthritis, and that a significant proportion of FMF patients with arthritis (13.5%) had moderate-high titers of anti-CCP. Therefore, anti-CCP antibodies may not be a reliable indicator to differentiate between FMF arthritis and rheumatoid arthritis.
21078723 Cardiovascular disease is related to hypertension in patients with rheumatoid arthritis: a 2011 Feb OBJECTIVE: To evaluate the incidence of cardiovascular disease (CVD) among Greek patients with rheumatoid arthritis (RA) under medical followup, and to assess the contribution of traditional CVD and RA-specific factors associated with CVD development. METHODS: This is a historic cohort study; information was collected from medical records of patients who had > 2 years' followup. Sociodemographic, clinical, laboratory, and therapeutic variables were evaluated for association with development of CVD. RESULTS: A total of 325 RA patients were studied: 250 women, mean age at RA onset 44 ± 15 years, and 75 men, mean age at RA onset 51 ± 15 years; median followup was 10 years. Fourteen women (5.6%) and 12 men (16%) developed CVD (p = 0.004). Multi-adjusted analysis revealed that hypertension (hazard ratio 3.76, 95% CI 0.99-15.06) was associated with incidence of CVD; late age at disease onset (HR 1.07, 95% CI 1.04-1.11), elevated C-reactive protein (CRP) level 1 year after start of followup (HR 1.03, 95% CI 1.00-1.05), and leflunomide treatment (HR per 1 year of treatment = 1.02, 95% CI 1.00-1.05) were also positively associated with CVD development. CONCLUSION: Hypertension was an important risk factor for CVD development in patients with RA. Late RA onset and inadequate early control of disease activity (as attested by CRP) remain additional risk factors. Leflunomide treatment may have a contributing effect. Early and effective treatment of RA and strict control of hypertension may modify the burden of CVD in RA patients.
20538233 Increased expression of suppressor of cytokine signaling 1 mRNA in patients with rheumatoi 2010 Jun The objective of this study was to investigate the associations between suppressor of cytokine signaling 1 (SOCS1) mRNA expression and SOCS1 polymorphisms with the development of rheumatoid arthritis (RA). One hundred and eighty-one patients with RA and 96 healthy controls were enrolled in this study. The SOCS1 mRNA level in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction. SOCS1 polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. We found that the expression of SOCS1 mRNA in PBMCs was significantly greater in patients with RA than in healthy controls. There were no significant differences in the expression of SOCS1 mRNA among patients with different disease activities. The increment in SOCS1 mRNA after stimulation with various cytokines was slightly lower in the patients with RA than in the healthy controls. This study also demonstrated that the SOCS1 polymorphisms were not associated with susceptibility to RA. In conclusion, the expression of SOCS1 mRNA in PBMCs is higher in patients with RA than in healthy controls. The increment in SOCS1 mRNA expression in PBMCs after stimulation with different cytokines seems to be lower in patients with RA than in healthy controls.
20436910 Paradoxical association of C-reactive protein with endothelial function in rheumatoid arth 2010 Apr 27 BACKGROUND: Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA). METHODOLOGY/PRINCIPAL FINDINGS: Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01). CONCLUSIONS/SIGNIFICANCE: These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability.
20047521 LTB4 can stimulate human osteoclast differentiation dependent of RANKL. 2010 Our previous study showed that Leukotriene B4 can directly stimulate osteoclast differentiation independent of RANKL. In order to determine whether Leukotriene B4 could indirectly stimulate human osteoclast differentiation through increasing RANKL expression of rheumatoid arthritis fibroblast-like synoviocytes, we utilize the coculture model of rheumatoid arthritis fibroblast-like synoviocytes and monocyte, which were stimulated in the presence of 2.5 ng/ml M-CSF in the control group, 2.5 ng/ml M-CSF+10(-8)M LTB4 in the experimental group a, and 2.5 ng/ml M-CSF+10(-8)M LTB4+100 ng/ml OPG in the experimental group b. After culture for 3 weeks, the number of multinucleated TRAP staining positive osteoclast-like cells stained with TRAP was counted to evaluate the differentiation effect in each group. There was almost no osteoclast-like cell in the control group and the experimental group b. There were many osteoclast-like cells in the experimental group a. These results indicated that Leukotriene B4 is capable of inducing osteoclast differentiation by a RANKL-dependent mechanism.
20822710 Functional evaluation of TNFAIP3 (A20) in rheumatoid arthritis. 2010 Sep OBJECTIVES: To determine the protein expression of TNFAIP3 in synovium and to show the capability of 6q23 intergenic SNPs, associated with rheumatoid arthritis (RA) susceptibility, to influence TNFAIP3 gene transcription. METHODS: Immunohistochemistry for TNFAIP3, NF-kB p65 and phosphorylated NF-kB p65 protein expression was performed in 6 RA knee joint synovium samples compared to 9 osteoarthritis (OA) samples. Luciferase reporter gene assays were used to examine the regulatory ability of RA associated SNP variants on TNFAIP3 promoter activity. Sense and antisense constructs were prepared for rs6920220 alleles, together with each of the 4 SNPs in r2=1 with it (rs6933404, rs2327832, rs6927172 and rs17264332), coupled to the TNFAIP3 promoter. Transient transfections were performed in a human T lymphoblastoid (CEMC7A) cell line. Bioinformatic software was utilised to prioritise SNPs for further investigation. Electrophoretic mobility shift assays (EMSA), using CEMC7A nuclear extracts, were conducted for the rs6927172 SNP alleles. RESULTS: TNFAIP3 protein expression was seen in the synovium samples and differential TNFAIP3 protein expression between RA vs. OA synoviocytes observed. Within RA synoviocytes TNFAIP3 expression is predominately cytoplasmic, whereas in OA its expression is strongly nuclear and cytoplasmic. For 3 of the 5 SNPs investigated (rs6920220, rs6933404, rs6927172) evidence of repressor activity of TNFAIP3 transcription was seen and EMSA data showed evidence of differential transcription factor binding to rs6927172 alleles. CONCLUSIONS: This is the first observation of TNFAIP3 protein expression in RA and OA synovium. In vitro analysis of 6q23 intergenic SNPs supports the possibility of the functional regulation of TNFAIP3.
19522451 [Spinal cord compression due to benign osteoporotic vertebral fracture]. 2009 Feb BACKGROUND: A neurologic compromise associated with vertebral fractures is generally due to a malignancy causes. Therefore, an osteoporotic vertebral fracture can sometimes cause neurologic complications. AIM: Report a case of neurologic compromise associated with osteoporotic vertebral fractures. OBSERVATION: A-62-year-old man suffered from rheumatoid arthritis since 1985, presented a cervical pain associated with quadriparesia secondary to a C5 osteoporotic vertebral fractures. CONCLUSION: Osteonecrosis may be the cause of neurologic compromise associated with osteoporotic vertebral fractures.
19833759 Reevaluation of the role of duration of morning stiffness in the assessment of rheumatoid 2009 Nov OBJECTIVE: To evaluate the utility of the duration of morning stiffness (MS), as a patient-reported outcome (PRO), in assessing rheumatoid arthritis (RA) disease activity. METHODS: We acquired information on 5439 patients in QUEST-RA, an international database of patients with RA evaluated by a standard protocol. MS duration was assessed from time of waking to time of maximal improvement. Ability of MS duration to differentiate RA activity states, based on Disease Activity Score (DAS)28, was assessed by analysis of variance; and a receiver-operating characteristic (ROC) curve was plotted for discriminating clinically active (DAS28 > 3.2) from less active (DAS28 3.2). CONCLUSION: MS duration has a moderate correlation with RA disease activity. Assessment of MS duration may be clinically helpful in patients with low RAPID3 scores.