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ID PMID Title PublicationDate abstract
22841864 Inflammatory arthritis as a novel risk factor for cardiovascular disease. 2012 Oct Cardiovascular disease (CVD) comorbidity is a significant issue for the inflammatory arthritides (IA). There is a wealth of mortality studies showing increased cardiovascular mortality in rheumatoid arthritis (RA) and the evidence suggests that the same is likely to be true of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). CVD co-morbidity is due to ischaemic pathologies driven by accelerated atherosclerosis and relates to the increased prevalence and clustering of classical risk factors, which may also be affected by treatments for IA, and their interplay with novel risk factors, namely systemic inflammation. Currently we are unable to quantify the contribution that classical and novel risk factors make to an individuals' CVD risk and specific algorithms need to be developed and validated in RA, PsA and AS to facilitate clinical management. Furthermore, large clinical trials are required to assess the effect of lifestyle modifications, primary prevention strategies and effective immunosuppression on hard CVD endpoints. However, in the meantime, a pragmatic approach should be adopted towards CVD risk management. Consensus opinion has generated guidelines for the management of CVD risk in IA and we discuss the importance of assessing each individual for CVD risk and establishing a system for routine risk factor identification alongside a commitment to treat identified risk factors to specific targets.
22541529 Management of the rigid arthritic flatfoot in the adults: alternatives to triple arthrodes 2012 Jun Every alternative to triple arthrodesis in the rigid acquired flatfoot deformity is predicated on limiting the patient exposure to the complication associated with triple arthrodesis. When possible, avoiding arthrodesis of either the talonavicular and calcaneocuboid joints, with their higher nonunion rates, seems a cogent option. Successful treatment is dependent on thoughtful patient evaluation and examination, meticulous joint preparation, careful positioning with rigid fixation, and judicious use of adjunctive procedures to achieve the goal of a plantigrade foot that functions well and is minimally painful.
22187357 Disparity in disaster preparedness among rheumatoid arthritis patients with various genera 2012 Jul OBJECTIVES: To describe disaster preparedness among chronically ill patients and to examine how differences in health, functional, and disability conditions are associated with disaster preparedness, focusing on rheumatoid arthritis (RA) patients with various functional and disability levels. METHODS: In 2007, 1,477 members of a nationwide RA patient group in Japan who lived in municipalities affected by natural disasters between 2004 and 2006 were asked to participate in a questionnaire survey. Three medical preparedness indicators, namely, medication stockpiles, the carrying of medications, and the carrying of prescription/treatment records, and three general preparedness indicators, namely, having emergency packs, emergency communication plans, and emergency evacuation plans, were used as dependent variables. Multivariable logistic models were applied to examine the associations of health-related vulnerability variables with the preparedness variables. RESULTS: Of the 553 subjects included into the analysis, only one-half had taken medical preparedness measures and only one-quarter had taken general preparedness measures. Although physical disability and poorer functional level were associated positively with the medical preparedness, those with poorer perceived health were less likely to carry medications and prescription/treatment records, and those receiving the highest long-term care levels were less likely to carry medications than their healthier counterparts. CONCLUSIONS: Among the population of chronically ill RA patients surveyed, disaster preparedness was insufficient, and their preparedness status varied with health, functional, and disability conditions. We suggest that policy-makers should give careful thought to the targets they set for disaster preparedness.
22828532 Comparative study on methotrexate and hydroxychloroquine in the treatment of rheumatoid ar 2012 Jul This study was done to see the efficacy and tolerability of methotrexate and hydroxychloroquine in the Treatment of Rheumatoid Arthritis. It was an open label controlled clinical trial, done in Mymensingh Medical college hospital. Fifty six patients were selected by random sampling method, 28 were included in methotrexate group and another 28 for hydroxychloroquine group using inclusion & exclusion criteria. Primary efficacy variables (DAS28, daily naproxen), secondary efficacy variables, and safety measurement variables studied both clinically & laboratory investigations. The data were analyzed by computer with the help of SPSS. The student's t test was used as test of significant. The mean age of the patients at diagnosis was almost identically distributed between methotrexate and hydroxychloroquine group (41.7±12.2 vs. 42.9±9.2 years, p=0.659). Disease activity at baseline was found to be almost homogeneous to each group except CRP which was observed to be significantly higher in methotrexate group than hydroxychloroquine group (p<0.001). Disease activity at 1 month of treatment reduced in the methotrexate group than those in hydroxychloroquine group (p<0.05 in each case). After 3 and 6 months of treatment, disease activity decreased significantly in both groups (p<0.001 and p<0.05 respectively). The average daily dose of NSAID (Naproxen) decreased significantly (p<0.001). Safety variables at 6 month were within normal physiological ranges and did not differ in groups (p>0.05) indicating that both methotrexate and hydroxychloroquine were effective and safe to use in rheumatoid arthritis. The difference in the incidence of adverse effects, total or individual, was almost nil.
21062340 Mechanism of alveolar bone loss in a collagen-induced arthritis model in mice. 2011 Feb OBJECTIVE: the aim of this study was to understand the cellular/molecular mechanisms of periodontal breakdown in a collagen-induced arthritis (CIA) model in mice to enhance the understanding of rheumatoid arthritis (RA)-associated alveolar bone loss in humans. MATERIALS AND METHODS: all analyses were performed on paired samples from CIA and control group mice. Mandibles were retrieved for micro-computed tomography (micro-CT), histomorphometric analysis, and isolation of alveolar bone cells (ABCs). In vitro osteoclastogenic/osteogenic/adipogenic potentials of ABCs were evaluated and the mRNA expression of downstream effector genes was assessed. Bone formation of ABCs was assessed using an ectopic transplantation model. RESULTS: histomorphometric and micro-CT data showed that alveolar bone loss was significantly increased in the CIA group (p<0.05). Osteoclastogenesis was significantly increased in the CIA group in vivo (p<0.05), with upregulated mRNA expressions of osteoclastogenesis-associated genes. Osteoblasts appeared to undergo increased apoptosis, and the bone-forming activity of ABCs concomitantly decreased with in vitro osteogenic differentiation and in vivo ectopic transplantation (p<0.05). Also, adipogenesis-associated mRNA expression was highly expressed in the CIA group, resulting in significantly enhanced adipocyte differentiation in vitro (p<0.05). CONCLUSIONS: these data demonstrate that increased osteoclastic activity, decreased bone-forming activity and enhanced adipogenesis promote alveolar bone loss in a CIA model in mice, and they suggest that these mechanisms could account for the same outcome in human RA.
22157597 Effectiveness of sulfasalazine and methotrexate in 1102 DMARD-naive patients with early RA 2012 Apr OBJECTIVE: To compare baseline characteristics, responses and drug survival in patients with early RA starting SSZ or MTX in a real-life setting. METHODS: The analyses included DMARD-naïve patients with RA (disease duration ≤ 1 year) starting SSZ or MTX. Three- and 6-month effectiveness was compared by unadjusted analysis and with adjustment for propensity score quintile. In addition, effectiveness in SSZ- and MTX-treated patients matched for RF status and baseline DAS-28 was compared. RESULTS: SSZ-treated patients (n = 175) had lower baseline disease activity than patients treated with MTX (n = 927) [mean 28-joint DAS (DAS-28) 4.4 vs 5.0, P < 0.001], and were less often RF positive (50 vs 61%, P = 0.006). Six-month mean ΔDAS-28 was smaller with SSZ than MTX (-1.0 vs -1.5, P = 0.003); the difference was not significant after adjustment for propensity score quintile (P = 0.36). For SSZ/MTX, 3-month ACR50 and European League Against Rheumatism (EULAR) good responses were 9/23% (P < 0.001) and 24/31% (P = 0.14), respectively. Three-year drug survival was superior for MTX (P < 0.001) and estimated 1-year survival rates were 42/75% for SSZ/MTX. In patients matched for baseline DAS-28 and RF, mean ΔDAS-28 (MTX -1.2, P = 0.55 vs SSZ) and EULAR good responses (39 vs 37%, P = 0.74) were similar at 6 months; drug survival was superior for MTX (P < 0.001). CONCLUSION: Patients treated with SSZ as first DMARD were more often RF negative and had lower baseline disease activity. Drug survival was superior for MTX, and effectiveness was greater with MTX than with SSZ although the difference was reduced when adjusting for differences in baseline characteristics.
21936794 Measurement and meaning of markers of reactive species of oxygen, nitrogen and sulfur in h 2011 Oct Reactive species of oxygen, nitrogen and sulfur play cell signalling roles in human health, e.g. recent studies have shown that increased dietary nitrate, which is a source of RNS (reactive nitrogen species), lowers resting blood pressure and the oxygen cost of exercise. In such studies, plasma nitrite and nitrate are readily determined by chemiluminescence. At sites of inflammation, such as the joints of RA (rheumatoid arthritis) patients, the generation of ROS (reactive oxygen species) and RNS overwhelms antioxidant defences and one consequence is oxidative/nitrative damage to proteins. For example, in the inflamed joint, increased RNS-mediated protein damage has been detected in the form of a biomarker, 3-nitrotyrosine, by immunohistochemistry, Western blotting, ELISAs and MS. In addition to NO•, another cell-signalling gas produced in the inflamed joint is H2S (hydrogen sulfide), an RSS (reactive sulfur species). This gas is generated by inflammatory induction of H2S-synthesizing enzymes. Using zinc-trap spectrophotometry, we detected high (micromolar) concentrations of H2S in RA synovial fluid and levels correlated with clinical scores of inflammation and disease activity. What might be the consequences of the inflammatory generation of reactive species? Effects on inflammatory cell-signalling pathways certainly appear to be crucial, but in the current review we highlight the concept that ROS/RNS-mediated protein damage creates neoepitopes, resulting in autoantibody formation against proteins, e.g. type-II collagen and the complement component, C1q. These autoantibodies have been detected in inflammatory autoimmune diseases.
23217265 Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for dis 2012 Dec 7 INTRODUCTION: The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA). METHODS: A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR. RESULTS: Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals. CONCLUSIONS: Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.
21833517 Lack of association between IL-6 gene polymorphisms and rheumatoid arthritis in Turkish po 2012 Jul Inflammatory cytokines play an important role in the pathogenesis of rheumatoid arthritis (RA). One of candidate genes is interleukin-6 (IL-6), and single-nucleotide polymorphisms in the promoter region of IL-6 were found to be associated with RA. The aim of this study was to determine the association between IL-6 promoter polymorphisms (-174, -572, -597) and RA in Turkish population. A total of 425 subjects were recruited into the study (247 healthy controls and 178 RA). The promoter region of IL-6 gene was amplified by PCR using DNAs from patients and the controls, and their PCR products were digested by suitable enzymes. No significant association was found between RA and -174 genotype distribution (P = 0.535) and allele frequency (P = 0.230). There was also no relationship between -572 (P = 0.150) and -597 (P = 0.912) gene polymorphism and RA. Our results suggested that IL-6 gene promoter polymorphisms have no association with RA in Turkish population.
21751228 Modeling subject-specific phase-dependent effects and variations in longitudinal responses 2011 Aug 30 We address statistical issues regarding modeling a collection of longitudinal response trajectories characterized by the presence of subject-specific phase-dependent effects and variation. To accommodate these two time-varying individual characteristics, we employ a geometric stochastic differential equation for modeling based on a Brownian motion process and develop a two-step paradigm for statistical analysis. This paradigm reverses the order of statistical inference in random effects model. We first extract individual information about phase-dependent treatment effects and volatility parameters for all subjects. Then, we derive the association relationship between the parameters characterizing the individual longitudinal trajectories and the corresponding covariates by means of multiple regression analysis. The stochastic differential equation model and the two-step paradigm together provide significant advantages both in modeling flexibility and in computational efficiency. The modeling flexibility is due to the easy adaptation of temporal change points for subject-specific phase transition in treatment effects, whereas the computational efficiency benefits in part from the independent increment property of Brownian motion that avoids high-dimensional integration. We demonstrate our modeling approach and statistical analysis on a real data set of longitudinal measurements of disease activity scores from a rheumatoid arthritis study.
21801346 Investigating a pathogenic role for TXNDC5 in rheumatoid arthritis. 2011 Jul 29 INTRODUCTION: Expression of TXNDC5, which is induced by hypoxia, stimulates cell proliferation and angiogenesis. Our previous study detected increased TXNDC5 expression in the synovial tissues of rheumatoid arthritis (RA) patients using proteomic methods. The current study investigated a pathogenic role for TXNDC5 in RA. METHOD: Expression of TXNDC5 in synovial membranes was quantitatively analyzed by immunohistochemistry, Western blotting and real-time polymerase chain reaction (PCR). Serum TXNDC5 levels and serum anti-TXNDC5 antibody levels were determined using sandwich enzyme-linked immunosorbent assay (ELISA). A total of 96 single nucleotide polymorphisms (SNPs) in or near the TXNDC5 gene were genotyped using custom-designed Illumina 96-SNP VeraCode microassay. Allele frequencies and genotype frequencies of SNPs were assessed using a case-control design in a cohort of 267 Chinese patients with RA, 51 patients with ankylosing spondylitis (AS) and 160 healthy controls. Additional genotyping of 951 patients with RA and 898 healthy controls was performed for four SNPs (rs2277105, rs369086, rs443861 and rs11962800) using the TaqMan method. RESULTS: Real-time PCR, Western blotting and immunohistochemistry detected significantly higher TXNDC5 expression in the synovial tissues of RA patients compared to samples from patients with osteoarthritis (OA) or AS. ELISA detected significantly higher levels of TXNDC5 in the blood of RA patients compared to OA, AS and systemic lupus erythematosus patients, and healthy controls. ELISA did not detect significantly different levels of anti-TXNDC5 antibody in the blood of RA, OA and AS patients and healthy controls. A total of 9 SNPs (rs9505298, rs41302895, rs1225936, rs1225938, rs372578, rs443861, rs408014, rs9392189 and rs2743992) showed significant association with RA, while 16 SNPs (rs1044104, rs1225937, rs1225938, rs372578, rs89715, rs378963, rs1225944, rs1225947, rs1238994, rs369086, rs408014, rs368074, rs1225954, rs1225955, rs13209404 and rs3812162) showed significant association with AS. Taqman SNP assay demonstrated that rs443861 has an association with RA, which correlates with the microassay results. CONCLUSIONS: TXNDC5 is up-regulated in synovial tissues of RA patients. TXNDC5 has a genetic effect on the risk of RA and AS.
22301823 Characteristics of late onset neutropenia in rheumatologic patients treated with rituximab 2012 Jun BACKGROUND: Late onset neutropenia (LON) secondary to rituximab has been reported as an adverse event in the treatment of hematological malignancies but reports on autoimmune diseases are scarce. AIM: To review the characteristics of LON in rheumatologic patients from a single center. DESIGN: Retrospective case record study. METHODS: Clinical and laboratory data since the introduction of rituximab in our clinic in 2006 were collected and analyzed retrospectively. LON was defined as an absolute neutrophil count <1.0 × 10(9)/l occurring 4 weeks after the last rituximab infusion. RESULTS: LON was identified in eight patients (6% of all patients receiving rituximab). All patients had complicated and refractory disease and had been treated with a median of 4.5 different immunosuppressive drugs prior to rituximab. LON appeared after a median interval of 23 weeks with recovery of LON after a median of 6.5 days. Four patients had concomitant infection at the onset of neutropenia, when six patients had both low immunoglobulin M and immunoglobulin G. Six patients were rechallenged with rituximab without recurrence of LON. CONCLUSION: The characteristics of LON after rituximab treatment in patients with autoimmune disease are comparable with experiences from hematological malignancies. LON seems to precede B-cell recovery implying a perturbation of the granulocyte homeostasis. LON with its rapid recovery does not seem to increase the risk for serious infection in contrast to the sustained hypogammaglobulinemia that may follow rituximab. The risk of LON recurrence after rechallenge is low.
22967804 Combined therapeutic application of mTOR inhibitor and vitamin D(3) for inflammatory bone 2012 Dec Inflammatory bone destruction is a prominent feature and a cause of substantial morbidity in several inflammatory diseases, including rheumatoid arthritis (RA), periodontitis, and peri-prosthetic loosening. Osteoclasts are unique, multinucleated giant cells that effectively resorb bone and thus are directly responsible for bone destruction in several inflammatory diseases. PI3K/Akt/mTOR pathway has been well known to play important roles in regulating adaptive and innate immune cell function. In addition to play roles in immune responses, several lines of evidence demonstrate that PI3K/Akt/mTOR pathway is critical for osteoclast differentiation and survival. These results suggest that inhibition of PI3K/Akt/mTOR pathway could protect against bone destruction in inflammatory diseases, including RA. However, the clinical use of mTOR inhibitors may be hampered due to limited clinical efficacy and frequent toxic side effects. In the treatment of RA, combination therapy with various disease-modifying antirheumatic drugs (DMARDs) has been suggested to improve the therapeutic efficacy and limit the side effects. In this report, we show several experimental evidences that vitamin D(3) modulates mTOR pathway, and present a hypothesis that the combination of mTOR inhibitor and vitamin D(3) can effectively inhibit osteoclast differentiation and function in chronic inflammatory condition such as RA, therefore this combination will be a powerful therapeutic regimen in preventing the inflammation-induced bone destruction in RA.
20634036 No clear advantage to use of wound drains after unilateral total knee arthroplasty: a pros 2011 Jun We conducted a prospective randomized, controlled trial in 100 patients to compare the postoperative use of wound drains with the use of no drains in patients who underwent unilateral primary total knee arthroplasty to determine differences in blood loss, range of motion, wound healing, complications (deep vein thrombosis, wound infection), and need for blood transfusions. The patients, who underwent surgery between February 2006 and February 2007, were randomly divided into 2 groups of 50 each: group A, treated without a drain, and group B, treated with a drain. The between-group difference in total blood loss was significant: 535 ± 295 mL in group A and 853 ± 331 mL in group B. Group A needed comparatively less blood transfused than group B did. Differences in wound infection, incidence of deep vein thrombosis, and range of motion were not statistically significant between groups. We found no clear advantage to the use of wound drains in unilateral total knee arthroplasty.
22623332 α-Enolase expressed on the surfaces of monocytes and macrophages induces robust synovial 2012 Jul 1 α-Enolase (ENO1) is a multifunctional glycolytic enzyme expressed abundantly in the cytosol. It has been implicated in autoimmune and inflammatory diseases. Serum Abs against ENO1 were reported in rheumatoid arthritis (RA). Cell-surface expression of ENO1 has been found to be increased rapidly in response to inflammatory stimuli, but its expression and function has not been reported in RA. In this study, we show that cell-surface expression of ENO1 is increased on monocytes and macrophages isolated from RA patients but not on those from osteoarthritis patients, and Ab against ENO1 can stimulate these cells to produce higher amounts of proinflammatory mediators, such as TNF-α, IL-1 α/β, IFN-γ, and PGE(2) via p38 MAPK and NF-κB pathway. The frequency of ENO1-positive cells in synovial fluid mononuclear cells was higher than PBMCs. ENO1-positive cells were also found in the inflamed synovium from RA patients and arthritic ankle tissues of mice with collagen-induced arthritis. Taken together, these findings suggest that Abs against ENO1 present in RA sera may stimulate monocytes and macrophages expressing cell-surface ENO1 and contribute to production of proinflammatory mediators during the effector phase of synovial inflammation.
21914399 [Significance of anti-cyclic citrullinated peptide antibody and magnetic resonance imaging 2011 Jun 21 OBJECTIVE: To study the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) and magnetic resonance imaging (MRI) of metacarpophalangeal joints (MCP) and wrist in early rheumatoid arthritis (RA). METHODS: MRI of MCP and wrist joint, laboratory indices of anti-CCP and rheumatic factor (RF) were performed and recorded in the 94 early-stage RA patients, 24 non-typical monoarthritis and 35 other arthritis. The MRI findings and OMERACT (outcome measures in rheumatoid arthritis clinical trials) score were analyzed in comparison with their clinical and laboratory indices. RESULTS: The sensitivity of anti-CCP, synovitis, bone erosion and bone erosion was 55.3%, 100%, 25.5% and 88.3% respectively in early-stage RA patients. The specificity was 88.6%, 71.4%, 94.3% and 65.7% respectively. There was significant difference between early-stage RA group and other arthritis group (P < 0.05). Bone erosion was found to be the most specific among MRI findings. And bone erosion of wrist joint had a positive correlation with anti-CCP. MRI was a more efficient supplemental modality in diagnosing early-stage RA as compared with conventional radiological films. Among 94 early-stage RA, their MRI findings and OMERACT scores of wrist joint appeared more obvious. CONCLUSION: Anti-CCP has a better specificity for early-stage RA than RF. But MRI may visualize the disorder of RA earlier while it is often missed by radiological films. Both have prominent diagnostic values in early RA patients. Bone erosion of wrist joint has a positive correlation with anti-CCP. MRI may help to differentiate those RA patients with negative anti-CCP.
22931896 Voice symptoms in patients with autoimmune disease: a cross-sectional epidemiological stud 2012 Dec OBJECTIVE: To assess the prevalence and severity of voice symptoms in individuals with a diagnosis of autoimmune disease. STUDY DESIGN: Cross-sectional survey. SETTING: Study participants were recruited from a rheumatology tertiary referral clinic at Norfolk and Norwich University Hospital. SUBJECTS AND METHODS: A cross-sectional questionnaire analyzing 109 patients with autoimmune disease (rheumatoid arthritis, seronegative spondyloarthritis, connective tissue disease) and a control group of 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis). Main outcome measures were the Voice Handicap Index-10 (VHI-10), xerostomia scale, acid reflux inquiry, and anxiety/depression scale. RESULTS: Patients with autoimmune disease were more likely to experience voice symptoms as assessed by the VHI-10 questionnaire (P = .0035). Subgroup analysis showed autoimmune patients were more likely to report voice symptoms regardless of whether they were on a disease-modifying antirheumatic drug (DMARD; P = .0010) or non-DMARD (P = .017), suggesting autoimmune disease may be an independent risk factor from pharmacotherapy. Xerostomia was more common in an autoimmune population compared with the control group (P = .02). A positive correlation between xerostomia and VHI-10 scores was found for the DMARD group (Spearman rank coefficient = 0.49, P < .001). No significant difference in acid reflux inquiry (P = .44) or the anxiety/depression scale (P = .36) was found when comparing the autoimmune and control groups. CONCLUSION: Patients with autoimmune disease have increased likelihood of voice symptoms when compared with a control population with non-autoimmune disease. Further prospective studies to elucidate the cause of voice disorder would be valuable.
21906736 Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus er 2011 Dec OBJECTIVES: Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA. METHODS: Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses. RESULTS: WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44-271.77), obesity (OR 4.09, 95%CI 1.00-16.68) and WBV (OR 3.98; 95%CI 1.23-12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78-0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05-0.52) are negatively associated with cIMT. CONCLUSION: Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.
21467606 Association of PTPN22 1858T/T genotype with type 1 diabetes, Graves' disease but not with 2011 Apr The protein tyrosine phosphatase nonreceptor 22 gene (PTPN22) is an important negative regulator of signal transduction through the T-cell receptors (TCR). Recently a single-nucleotide polymorphism (SNP) 1858 C/T within this gene was shown to be a risk factor for several autoimmune diseases, such as rheumatoid arthritis (RA), Graves' Disease (GD), systemic lupus erythematosus (SLE), Wegener's granulomatosis (WG) and type 1 diabetes mellitus (T1D). The aim of this study was to analyze a possible association between 1858 C/T SNP and a number of autoimmune diseases, including RA, GD and T1D in Russian population. Patients with T1D, GD, RA and healthy controls were genotyped for the 1858 C/T SNP in PTPN22 gene. We found a significant association between PTPN22 1858 C/T SNP and T1D and GD. 1858T/T genotype was observed more frequently in T1D and GD patients compared to control subjects. No such association was observed for RA. In concordance with a previous data establishing PTPN22 1858 C/T SNP association with several autoimmune diseases, our findings provide further evidence that the PTPN22 gene may play an important role in the susceptibility to some autoimmune diseases.
20665032 Nicotine inhibits tumor necrosis factor-α induced IL-6 and IL-8 secretion in fibroblast-l 2012 Jan It was recently demonstrated that the cholinergic anti-inflammatory pathway can modulate host inflammatory responses via cholinergic mediators or via electrical stimulation of the vagus nerve. Here, we investigated whether nicotine, a selective cholinergic agonist, plays any anti-inflammatory role in rheumatoid arthritis fibroblast-like synoviocytes (FLS). We observed that low concentrations (0.1-100 μM) of nicotine did not affect FLS viability in lactate dehydrogenase release test or the MTT assay. Nicotine at concentrations of 0.1-10 μM dose reduced the protein and mRNA expression of IL-6 and IL-8 induced by tumor necrosis factor-α (TNFα). Nicotine also inhibited nuclear factor (NF)-κB (p65) translocation from the cytoplasm to the nucleus, based on Western blotting and immunocytochemical analysis. In conclusion, nicotine can inhibit the TNFα dependant inflammatory pathway in synoviocytes by suppressing the activation of the NF-κB pathway.