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ID PMID Title PublicationDate abstract
27026689 Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER stu 2016 Jun OBJECTIVE: To investigate whether an intensive early rheumatoid arthritis (RA) treat-to-target (T2T) strategy could be improved through the use of musculoskeletal ultrasound (MSUS) assessment of disease activity. METHODS: 111 newly diagnosed patients with RA or undifferentiated arthritis (symptom duration <1 year) were randomised to strategies that aimed to attain either DAS28-erythrocyte sedimentation rate (ESR)<3.2 (control) or a total power Doppler joint count≤1 during a combined DAS28-ESR/MSUS assessment (intervention). MSUS examination was indicated if: DAS28-ESR<3.2 or DAS28-ESR≥3.2 with two swollen joints. Step-up disease-modifying antirheumatic drug (DMARD) escalation was standardised: methotrexate monotherapy, triple therapy and then etanercept/triple therapy. American College of Rheumatology (ACR) core-set variables were assessed 3 monthly by a metrologist blinded to group allocation. MRI of dominant hand and wrist, and plain radiographs of hands and feet were undertaken at baseline and 18 months for grading by two readers using the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis MRI Scoring System (RAMRIS) and van der Heijde/Sharp Score, respectively. The coprimary outcomes were mean change from baseline of DAS44 and RAMRIS erosion score. RESULTS: Groups were matched for baseline clinical, demographic and radiographic features. The intervention group received more intensive DMARD therapy. Both groups demonstrated significant improvements in DAS44 (mean change: control -2.58, intervention -2.69; 95% CI difference between groups -0.70 to 0.48; p=0.72). There were no significant between-group differences for any ACR core-set variables, except DAS44 remission after 18 months (control 43%, intervention 66%; p=0.03). There was minimal progression of MRI and radiographic erosions and no difference in imaging outcomes or serious adverse event rates. CONCLUSIONS: In early RA, a MSUS-driven T2T strategy led to more intensive treatment, but was not associated with significantly better clinical or imaging outcomes than a DAS28-driven strategy. TRIAL REGISTRATION NUMBER: NCT00920478.
26048170 Predictive risk factors of serious infections in patients with rheumatoid arthritis treate 2016 Jun OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.
27019199 Neo-Epitopes--Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid 2016 OBJECTIVE: Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. METHODS: Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. RESULTS: C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. CONCLUSION: This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients.
26466448 [THE IDENTIFICATION OF SUB-POPULATIONS OF B-LYMPHOCYTES OF PERIPHERAL BLOOD USING TECHNIQU 2015 Jun The study was carried out to apply technique of flow cytofluorometry for immunofenotyping of sub-populations of B-cells of peripheral blood in healthy persons and patients with rheumatoid diseases. The samples included 27 healthy donors, 16 patients with rheumatoid arthritis and 9 patients with systemic lupus erythematosus. The peripheral blood of all participants was analyzed for relative number of CD19+B-cells, total population of memory B-cells (CD19+CD27+); unswitched (CD19+IgD+CD27+) and switched (CD19+IgD- CD27+) memory B-cells, naive (CD19+IgD+CD27-) and transitory (CD19+IgD+CD10+CD38++CD27-) B-cells, plasmablasts (CD19+CD38+++IgD-CD27+CD20+) and long-lived plasmatic cells (CD19+CD138+). The sub-populations of B-cells were identified by technique of multicolor flow cytofluorometry using panel of monoclonal antibodies to surface membrane markers of B-lymphocytes. In normal state, relative number (median-Me; interquartile range 25-75 percentiles) of CD19+B-lymphocytes amounted to 9.1 (6.6-11.6)%; CD19+CD27+memory B-cells - 2.2 (1.6-3.3)%; unswitched and switched memory B-cells - 10 (6.4-12.7)% and 17.7 (14.9-27.0)%; naive B-cells - 65.8 (55.1-73.4)%; transitory B-cells - 0.1 (0.1-0.3)%; plasmablasts - 7.0 (5.0-9.4)%. The long-lived plasmatic cells in peripheral blood were absent. In patients with rheumatoid arthritis percentage of content of total population of memory B-cells were lower than in donors (1.6; 1.00-2.3%; p = 0.038). Under systemic lupus erythematosus was detected decreasing of number of naive B-cells (40.2; 19.7-58.2) and increasing of level of switched memory B-cells (34.2; 21.0-52.7) as compared with donors (p = 0.003 in both cases). The study established no reliable differences between healthy donors and patients with rheumatoid arthritis and systemic lupus erythematosus in the rest of sub-populations of B-lymphocytes. The developed technique of multi-parametric flow cytofluorometry can be recommended for studying homeostasis of B-cells of peripheral blood in healthy persons and patients with auto-immune rheumatoid diseases and also for evaluating and forecasting effectiveness of anti-B-cells therapy.
25179377 Association between butyrylcholinesterase activity and phenotypes, paraoxonase192 rs662 ge 2015 Jan OBJECTIVES: Evidences indicate that oxidative stress and inflammation are important processes in the development of destructive synovial tissue in rheumatoid arthritis (RA). The two major bioscavenger enzymes that are associated with inflammation and oxidative stress are human-butyrylcholinesterase (BuChE) and paraoxonase-1 (PON-1). Thus, the objective of this study was to determine the relation of BuChE phenotypes and PON-1 Q192R polymorphism with inflammatory markers such as anti-cytroline circulated peptide (CCP)-antibodies, CRP, neopterin, DAS28-CRP in RA patients. DESIGN AND METHODS: In this study, we examined association of BuChE-phenotypes and activity, PON192rs662 (Q192R) polymorphism and its arylesterase activity (ARE) with systemic-inflammatory-markers and oxidative stress. The present case-control study consisted of 419-RA patients and 398 gender-age-matched unrelated healthy controls from west population of Iran. PON192rs662 polymorphism was detected by real-time-PCR. BuChE phenotype, TAC level, serum BuChE and ARE activities were determined spectrophotometrically. Anti-CCP-antibody and CRP were measured by ELISA and neopterin level was detected by HPLC. We used the EULAR activity criteria to measure DAS28-CRP. RESULTS: We found that PON-1-Q192R was associated with severity of RA [remission-to-low and moderate-to-high in dominant Q/Q+Q/R vs. R/R: OR=2.27, p<0.001; codominant Q/Q vs. R/R: OR=1.65, p<0.001 and Q/R vs. R/R: OR=2.12, p=0.003; recessive Q/Q vs. R/R+Q/R: OR=1.79, p=0.032; and allele Q vs. R: OR=1.68, p<0.001] and presence of anti-CCP-antibody (codominant model Q/Q vs. R/R: OR=1.28, p=0.042). The carriers of Q/Q genotype PON-1-Q192R and BuChE non-UU-phenotype had higher ARE activity, serum levels of neopterin, anti-CCP antibody titer and number of tender-joint and lower activity of BuChE and serum level of TAC than that of R/R genotype and BuChE-UU-phenotype. CONCLUSIONS: The current findings demonstrate for the first time that there is a link between systemic inflammatory markers, oxidative stress, the PON192rs662-Q allele and BuChE-non-UU-phenotype and their corresponding enzymatic activity which may be considered as a risk factor for the severity of RA for a population in Iran.
26605992 Examining Changes in Central and Peripheral Pain as Mediates of Fatigue Improvement: Resul 2016 Jul OBJECTIVE: Following anti-tumor necrosis factor (anti-TNF) therapy, improvements in rheumatoid arthritis (RA) fatigue are driven by reductions in pain. However, therapies may modify both central and peripheral pain. This study sought to examine the hypothesis that reductions in fatigue after anti-TNF therapy reflect changes in central, not peripheral, pain mechanisms. METHODS: Data came from patients with severe baseline fatigue (Short Form 36 health survey [SF-36] vitality scale ≤12.5; n = 2,652), recruited to the British Society for Rheumatology Biologics Register for RA for commencing anti-TNF therapies between October 2000 and November 2008. Data of interest comprised change over 6 months in fatigue, pain (SF-36 bodily pain scale), and disease activity constituents (Disease Activity Score in 28 joints, erythrocyte sedimentation rate [ESR], global health, swollen joints, and tender joints). Principal components factor analysis with varimax rotation determined latent variables of symptom change; variables were accepted provided they had eigenvalues ≥1. RESULTS: Six factors were identified, of which 2 met acceptance criteria (eigenvalues of 2.39 and 1.14, respectively). Following rotation, loadings indicated that factor 1 comprised markers of peripheral inflammation: change in ESR, swollen joints, tender joints, and global health. This distinct loading led to factor 1 being labeled peripheral inflammation. Conversely, factor 2 comprised change in pain, fatigue, and global health and an absence of peripheral inflammation markers and was therefore labeled central inflammation. CONCLUSION: Following anti-TNF therapies, reductions in fatigue and pain appear to reflect improvements in central, rather than peripheral, inflammation. Therefore, for those seeking to treat fatigue via pain mechanisms, improvements may be maximized by the application of treatment modalities that effectively target central mechanisms.
25633325 Skewing dendritic cell differentiation towards a tolerogenic state for recovery of toleran 2015 Jun To date, the available options to treat autoimmune diseases such as rheumatoid arthritis (RA) include traditional corticoids and biological drugs, which are not exempt of adverse effects. The development of cellular therapies based on dendritic cells with tolerogenic functions (TolDCs) has opened a new possibility to efficiently eradicate symptoms and control the immune response in the field of autoimmunity. TolDCs are an attractive tool for antigen-specific immunotherapy to restore self-tolerance in RA and other autoimmune disorders. A promising strategy is to inject autologous self-antigen-loaded TolDCs, which are able to delete or reprogram autoreactive T cells. Different protocols for the generation of stable human TolDCs have been established and the therapeutic effect of TolDCs has been investigated in multiple rodent models of arthritis. Pilot studies in humans confirmed that TolDC application is safe, encouraging clinical trials using self-antigen-loaded TolDCs in RA patients. Although an abundance of molecular regulators of DC functions has been discovered in the last decade, no master regulator of tolerogenicity has been identified yet. Further research is required to define biomarkers or key regulators of tolerogenicity that might facilitate the induction and monitoring of TolDCs.
26339140 Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis. 2015 OBJECTIVE: Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. METHODS: PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied. RESULTS: Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. CONCLUSIONS: This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.
29231407 [Long-snake moxibustion for rheumatoid arthritis:a randomized controlled trial]. 2016 Jul 12 OBJECTIVE: To observe the clinical efficacy differences among long-snake moxibustion, warm needling and western medication on rheumatoid arthritis and explore its effect mechanism. METHODS: One hundred and twenty patients were randomized into a long-snake moxibustion group, a warm needling group and a western medication group, 40 cases in each one. In the long-snake moxibustion group, the long-snake moxibustion was used. The ginger-isolated moxibustion was applied along the governor vessel, from Dazhui (GV 14) to Yaoshu (GV 2), once a month, for 2 months. In the warm needling group, the main points included Dazhui (GV 14), Ganshu (BL 18), Pishu (BL 20), Shenshu (BL 23), Zhiyang (GV 9), Mingmen (GV 4) and Yaoyangguan (GV 3). The warm needling technique was used at 4 to 5 points each time, and 3 moxa cones were required at each points. The treatment was given once every two days, for 2 months. In the western medication group, methotrexate was prescribed for oral administration, 10 mg each time, once a week. If the joint pain score or joint swelling score was up to 6, diclofenac sodium was combined, 25 mg each time, 3 times a day, for 2 months. The symptom score, physical sign score, the visual analogue scale (VAS) score, levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), immunoglobulin M (IgM) and immunoglobulin G (IgG) were observed before and after treatment in the patients of the three groups. RESULTS: The treatments relieved the symptoms and physical signs of rheumatoid arthritis and improved VAS score and the levels of serum RF, ESR, CRP, IgM and IgG in all of the three groups (all P<0.01). The efficacy in the long-snake moxibustion group was significantly better than that in the warm needling group and the western medication group (P<0.05, P<0.01). CONCLUSIONS: The long-snake moxibustion achieves the significant clinical efficacy on rheumatoid arthritis, better than warm needling therapy and methotrexate. This therapy much better reduces immune response and alleviates the sickness.
27795502 [Monocyte/Macrophage and TNFα-induced adipose related protein (TIARP) in rheumatoid arthr 2016 In the pathogenesis of rheumatoid arthritis (RA), TNFα and IL-6 are proved to be crucial cytokines. Monocyte and macrophage are thought to produce these cytokines, as well as the source of cells becoming osteoclast in RA. In this review, I will discuss the role of monocyte/macrophage and the recent topic of negative regulator of arthritis such as TNFα-induced adipose related protein in RA.
26352213 Study of novel molecular probe 99mTc-3PRGD2 in the diagnosis of rheumatoid arthritis. 2015 Dec INTRODUCTION: Angiogenesis in the synovial membrane plays an important role in the pathogenesis of rheumatoid arthritis (RA). Radiolabeled RGD (Arg-Gly-Asp) peptides can be used as a molecular probe in radionuclide imaging to assess angiogenesis noninvasively in vitro and investigate the process of RA to achieve the goal of early diagnosis and monitoring. The main objective of this study is to evaluate the value of RGD peptides conjugate with Tc-radiolabeled, Tc(HYNIC-3PRGD2)(tricine) (TPPTS) (Tc-3PRGD2 in short) in the diagnosis of RA. MATERIALS AND METHODS: Tc-3PRGD2 was synthesized using an HYNIC-3PRGD2 lyophilized kit with TcO4 labeling. Biodistribution and planar imaging studies were carried out in an RA rat model. The ankles were marked by arthritis index (AI) scores (from 0-3 score) according to the degree of ankle swelling and the ankle uptake of Tc-3PRGD2 was compared. Immunohistochemical staining was used to test the expression of integrin αvβ3 in the ankle tissue, analyzing the correlation between uptake of Tc-3PRGD2 and receptor expression. RESULTS: Planar imaging of arthritic ankles became visible at 30 min postinjection of Tc-3PRGD2 and was still clear at 6 h postinjection. The AI score increased, along with the uptake of Tc-3PRGD2. A biodistribution study showed that Tc-3PRGD2 was excreted by the urinary system. The uptake by ankles with different AI scores was 0.64±0.07%ID/g (0 score), 1.10±0.07%ID/g (1 score), 1.30±0.04%ID/g (2 score), and 1.73±0.05%ID/g (3 score), respectively, at 1 h postinjection, suggesting that the ankle uptake increased with an increase in the AI score. There was a linear positive correlation relationship (r=0.852, P<0.05) between the ankle uptake of Tc-3PRGD2 and the integrin αvβ3 expression levels in immunohistochemical study. CONCLUSION: Tc-3PRGD2 is a promising radiotracer for the diagnosis of RA.
25048740 Are men at greater risk of lean mass deficits in rheumatoid arthritis? 2015 Jan OBJECTIVE: We aimed to determine if there were sex differences in lean body mass (LBM) in patients with rheumatoid arthritis (RA) when compared with sex- and race-specific National Health and Nutrition Examination Survey (NHANES) reference data, and to investigate the impact of sex differences in risk factors for LBM deficits. METHODS: Dual x-ray absorptiometry measures of whole body LBM and appendicular LBM (arms and legs, appendicular lean mass [ALM]) were obtained on a total of 190 subjects from 2 independent cohorts (141 from San Francisco [SF], 49 from Philadelphia [PA]), expressed as indices adjusted for height (LBM index and ALM index, kg/m(2) ), and converted to sex- and race-specific Z scores relative to age and based on NHANES data. Sarcopenia was defined using 4 different sex-specific definitions. Multivariable linear and logistic regression analyses adjusted for disease activity, disease duration, physical activity, anti-cyclic citrullinated peptide seropositivity, fat mass index, and glucocorticoid use. RESULTS: While there were significant differences between the 2 cohorts, ALM index Z scores were significantly lower in men compared to women in both (SF: -1.43 versus -0.43, P < 0.0001; PA: -0.83 versus -0.06, P = 0.03). Observed sex differences were significant after adjustment in multivariable analyses within both cohorts. Odds of sarcopenia were 3 to 8 times greater in men in the SF cohort. Men in the PA cohort also had a higher, but nonsignificant, risk of sarcopenia. CONCLUSION: RA is associated with significant LBM deficits, with greater deficits observed in men. Future study may help elucidate the mechanisms driving greater deficits among men.
27247434 The short-term effects of two high-dose, step-down prednisolone regimens on body compositi 2016 Sep OBJECTIVE: To investigate the effect of two different high-dose, step-down prednisolone regimens on body composition in early RA patients after 26 weeks of treatment. METHODS: Prednisolone-naive patients with recent-onset RA (n = 108) were randomized to either COBRA (prednisolone 60 mg/day, tapered to 7.5 mg/day in 6 weeks; MTX and SSZ) or COBRA-light therapy (prednisolone 30 mg/day, tapered to 7.5 mg/day in 8 weeks and MTX). Body composition was assessed at baseline (before or soon after start of treatment) and after 26 weeks with DXA, and recorded as total body mass (TBM), total fat mass (FM), total lean mass (LM) and trunk/peripheral fat ratio. Log-ratio analyses assessed the proportional distribution of TBM (between LM, FM and bone mass) and FM (between trunk, extremities and head). The subgroup of patients with a DXA before start of treatment (n = 38) was analysed separately. RESULTS: In the subgroup of patients with a DXA before start of treatment, TBM increased by 1.6 kg (P < 0.001) and total FM by 1.3 kg (P < 0.001). The trunk/peripheral fat ratio and the proportional distribution of TBM and FM remained stable over time. There were no differences between the treatment groups. Similar results were obtained in the study population as a whole. CONCLUSION: Both high-dose, step-down prednisolone regimens caused increases in TBM, mainly caused by an increase in FM, but we found no fat redistribution from peripheral to central tissues. This absence in fat redistribution contradicts the widely held assumption of rapid adverse effects of prednisolone on body composition in RA. TRIAL REGISTRATION: ISRCTNregistry, http://www.isrctn.com, ISRCTN55552928.
25922848 Low baseline interleukin-17A levels are associated with better treatment response at 12 we 2015 T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA) pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin- (IL-) 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28) remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P = 0.032). DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P = 0.045) and 24 weeks (P = 0.046) after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.
25634192 Recognizing rheumatoid arthritis: oncoprotein survivin opens new possibilities: a populati 2015 Jan Survivin is a biomarker of cancer known for its anti-apoptotic and cell-cycle regulating properties. In the context of non-cancer pathology, high levels of survivin may be measured in blood and synovial fluid of patients with rheumatoid arthritis (RA) and associate with early joint damage and poor therapy response. The aim of the study was to investigate the value of survivin measurements in blood for diagnosis of RA in the frame of the Malaysian epidemiological investigation of rheumatoid arthritis (MyEIRA) study. The study enrolled RA patients from eight rheumatology centres in Peninsular Malaysia. The healthy controls matched by age, gender and ethnicity were recruited on the community basis from the residential area of the patients. Levels of survivin were measured in blood of RA patients (n = 1233) and controls (n = 1566) by an enzyme-linked immuno-sorbent assay (ELISA). The risk for RA was calculated as odds ratio (OR) and 95% confidence intervals in the individuals with high levels of survivin. The risk was calculated in relation to antibodies against cyclic citrullinated peptides (ACPA), detected by ELISA and HLA-DRB1 shared epitope (SE) alleles, identified by the polymerase chain reaction using sequence specific oligonucleotide method. High levels of survivin were detected in 625 of 1233 (50.7%) RA cases and in 85 of 1566 (5.4%) controls, indicating its high specificity for RA. Survivin was association with an increase in RA risk in the patients having neither SE-alleles nor ACPA (OR = 5.40, 95% CI 3.81-7.66). For the patients combining survivin, SE, and ACPA, the estimated risk for RA was 16-folds higher compared to the survivin negative patients with SE and ACPA(OR = 16.21, 95% CI 5.70-46.18). To conclude, detection of survivin in blood provides a simple test to improve diagnostic and to increase predictability for RA.
25608674 [Effector T cells]. 2015 Feb BACKGROUND: Although the present understanding of the immunopathogenesis of rheumatoid inflammation is still incomplete, there is substantial evidence that effector CD4+ T helper (Th) cells play a central role. RESULTS: In recent years, in addition to the established Th cell subsets Th1 and Th2 cells, other subsets, such as Th9, Th17, Th22 and T follicular helper (Tfh) cells have been described. Defining the contribution of T cells in the initiation and maintenance of inflammation has been augmented by the identification of functionally distinct subsets of effector Th cells that can be classified based on their cytokine and transcription factor profiles. CONCLUSION: Increasing knowledge of the role of these various T cell populations in chronic inflammation provides a better understanding and insights into the pathogenic mechanisms and chronification of rheumatic diseases.
27698401 Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF 2018 Jan Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).
27695991 The functional variants of endothelial nitric oxide synthase gene associated with rheumato 2017 Mar This study aimed to investigate whether functional variants of endothelial nitric oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA) ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants are responsible for alteration of the NO level in plasma, by reducing/increasing the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell of RA patients. For the control, blood samples obtained from 70 healthy persons were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or PCR technique. The data obtained was compared in itself and response to therapy. We found that "TT genotypic frequency" for the G894T variant was significantly associated with RA with an overall risk of 8.3-fold (p 0.029). No association was identified between intron 4 VNTR A/B variant and RA. At the 6 months, the mean visual analog scale (VAS), health assessment questionnaire (HAQ), and disease activity score for 28 joints (DAS 28) improvement was not significant among groups. Improvement in DAS was significantly better in anti-TNF treatment than disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We report for the first time that variants in the eNOS "TT" genotype might be contributed to the increased risk of RA in the Turkish population. These results imply that functional variants of eNOS gene might have an effect on RA patients and response to anti-TNF treatment. In addition, the results suggest that eNOS variants might be associated and affect host susceptibility and/or response to treatment in Turkish RA patients.
26316061 Agreement in assessment of infliximab and adalimumab levels in rheumatoid arthritis: inter 2015 Sep OBJECTIVES: Infliximab (IFX) and adalimumab (ADL) drug levels and anti-drug antibodies (ADA) are assessed using a variety of techniques, therefore, results cannot accurately be compared for clinical purposes. The aim of this study was to test two infliximab (IFX) and adalimumab (ADL) ELISA versions, for drug levels and ADA, to see whether they yield similar results. METHODS: ELISA versions [Promonitor® IFX R1 and R2 (V.1), Promonitor® IFX and Anti-IFX (V.2); Promonitor® ADL R1 and R2 (V.1), Promonitor® ADL and Anti-ADL (V.2) kits (Progenika Biopharma, Spain)] were used to measure drug levels and ADA in IFX (n=24) and ADL (n=24) rheumatoid arthritis-treated patients in three independent laboratories. Quantitative and qualitative agreements were evaluated using intraclass correlation coefficients (ICC), and Cohen's Kappa (κ) respectively. The Bland-Altman plots assessed differences between V.1 and V.2. RESULTS: Interlaboratory agreement (ICC/κ) with V.1 was poor for IFX (0.66/0.62) and ADL (0.69/0.52) drug levels; meanwhile, high agreement was found with V.2 for IFX (0.98/0.95) and ADL (0.094/1.00). Comparison between V.1 and V.2 in each laboratory resulted in systematically higher values in V.2 than in V.1 and poor agreement (ICC/κ ranges) for IFX (0.12-0.7/ 0.19-0.42) and ADL (0.69-0.89 /0.50-0.73). CONCLUSIONS: Qualitative measurements result in better agreement, as evidenced in our study. Greater agreement in V.2 compared with V.1 for IFX and ADL levels could be due to a better tune up. Further studies are required to standardise methods to establish therapeutic reference ranges.
27927025 "Whenever I can I push myself to go to work": a qualitative study of experiences of sickne 2018 Feb PURPOSE: UK government policy emphasizes the importance of continuing to work for recovery from poor health, yet sickness presenteeism (going to work whilst ill) is commonly regarded as having negative consequences for organizations and individuals. Our study explores experiences of working after onset of rheumatoid arthritis (RA), a chronic musculoskeletal disorder characterized by high rates of work disability. MATERIALS AND METHODS: An exploratory qualitative study consisting of in-depth interviews and six-month follow-up with 11 men and women with RA employed at disease onset. RESULTS: We expand upon previous models of sickness presenteeism by distinguishing between presenteeism that occurs voluntarily (wanting to work despite illness) and involuntarily (feeling pressured to work when ill). RA onset affected participants' ability to work, yet motivation to remain working remained high. The implementation of workplace adjustments enabled participants to stay working and restore their work capacity. Conversely, managers' misinterpretation of organizational sickness absence policies could lead to involuntary presenteeism or delayed return to work, conflicting with the notion of work as an aid to recovery. CONCLUSION: Workplace adjustments can facilitate voluntary sickness presenteeism. To reduce work disability and sickness absence, organizational policies should be sufficiently flexible to accommodate the needs of workers with fluctuating conditions. Implications for rehabilitation Individuals with rheumatoid arthritis (RA) are at high risk of work disability. Individuals' motivation to remain in work following onset of RA remains high, yet sickness presenteeism (working while ill) has received largely negative attention. It is important to distinguish between voluntary and involuntary forms of sickness presenteeism. Workplace adjustments facilitate voluntary sickness presenteeism (wanting to work despite illness) and improve job retention and productivity among workers with RA. Involuntary presenteeism (feeling pressured to work while ill) may occur if organizational policies are not sufficiently flexible to accommodate the needs of workers with RA.