Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
21710357 Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab ver 2012 Feb A retrospective study of 39 rheumatoid arthritis (RA) patients with an inadequate response to infliximab was conducted. The responses of subjects switching from infliximab to tocilizumab (n = 23) were compared to those of subjects switching to etanercept (n = 16). Disease activity was assessed by the Disease Activity Score 28-CRP ([C-reactive protein] DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Twenty-two patients completed 48 weeks of tocilizumab treatment, and 15 patients completed 48 weeks of etanercept treatment. In both treatment groups, 1 patient each discontinued treatment because of lack of efficacy. No serious adverse events occurred during the study, and no patients in either group withdrew due to adverse events. At week 48, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values after switching to either tocilizumab or etanercept, and there was no significant difference in efficacy, as measured by the DAS28-CRP, SDAI, and CDAI, between the two treatment groups (p = 0.12, 0.76, and 0.86, respectively). These results suggest that safety and tolerability were similar for both treatments. A switch from infliximab to either tocilizumab or etanercept in patients with RA who have not responded to infliximab is a feasible, well-tolerated treatment option.
21140264 Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and ero 2012 Mar Reports suggest leptin, which was initially described as a hormone that regulates food intake and energy balance, has an intimate relationship, and interacts with the immune system. Leptin consumption in the synovial cavity in patients with rheumatoid arthritis (RA) reported to have protective effect against erosion. To determine the difference in serum leptin and synovial/serum leptin ratio between RA and control and to assess whether these parameters correlate with systemic inflammation in RA. Also, the hypothesis that synovial/serum leptin ratio could be linked to joint erosion in RA was evaluated. The study subjects consisted of 40 consecutive patients with RA, 30 patients of them had knee effusion, and 30 controls. Ten of these controls had acute knee injury and their synovial fluid was obtained for comparison of synovial/serum leptin ratio with patients with RA. The mean serum leptin in patients with RA was significantly higher than controls. Also, the synovial leptin and synovial/serum leptin ratio in the RA patients with effusion was significantly higher than in the 10 control subjects with traumatic effusion. Serum leptin in the 30 RA patients with effusion was higher than the matched synovial leptin. In RA patients with effusion, synovial/serum leptin ratio was also significantly higher in RA patients with erosion than RA patients without erosion. Serum leptin level and synovial/serum leptin ratio are significantly correlated with the RA duration, DAS28, ESR, CRP, TNF-α, and IL-6. Finally, in regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. In RA, there is a significant increase in circulating leptin levels and synovial/serum leptin ratio compared to non-RA controls. Serum leptin and synovial/serum leptin ratio are significantly in erosive RA than non-erosive RA. Both parameters are correlated with disease duration and parameters of RA activity. In regression analysis, only the synovial/serum leptin ratio was positively associated with erosion in patients with RA. These results indicate that local consumption of leptin in the joint cavity has a protective role against the destructive course of RA.
21473861 Increased serum levels of β₂-GPI-Lp(a) complexes and their association with premature a 2011 Jul 15 BACKGROUND: Our recent study found the existence of complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a)[Lp(a)] in circulation and the complex concentrations were increased in sera of systemic lupus erythematosus patients. The concentration of β₂-GPI-Lp(a) and its relationship with premature atherosclerosis were evaluated in rheumatoid arthritis (RA) patients. METHODS: Serum concentrations of β₂-GPI-Lp(a) were measured in 53 active RA patients and 40 healthy controls by a "sandwich" ELISA. β₂-GPI-ox-LDL, ox-Lp(a), ox-LDL and anti-β₂-GPI were also measured by ELISAs. In addition, inflammatory markers were examined. RESULTS: Serum β₂-GPI-Lp(a) (1.12±0.25 U/ml vs. 0.87±0.19 U/ml, P<0.0001) and β₂-GPI-ox-LDL (1.01±0.20 U/ml vs. 0.80±0.08 U/ml, P<0.0001) concentrations in RA were both significantly higher than those of controls. Ox-Lp(a) (8.38±6.69 mg/l vs. 5.49±4.31 mg/l, P<0.05) and ox-LDL (0.68±0.65 mg/l vs. 0.37±0.13 mg/l, P=0.001) were also higher in RA than in controls. The area under the ROC curve (AUC) for β₂-GPI-Lp(a) (0.787) was larger than for ox-Lp(a) (0.731). AUC of β₂-GPI-ox-LDL (0.858) was also larger than for ox-LDL (0.785). β₂-GPI-Lp(a) and β₂-GPI-ox-LDL were positively correlated with ox-Lp(a), ox-LDL and CRP, respectively. CONCLUSIONS: β₂-GPI-Lp(a) complex concentrations increased in active RA. Inflammation and oxidative stress in RA contribute to the increase of ox-Lp(a) and subsequently the formation of β₂-GPI-Lp(a).
22454398 Definition of treatment response in rheumatoid arthritis based on the simplified and the c 2012 Jul BACKGROUND: The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) are established instruments to measure disease activity in rheumatoid arthritis (RA). To date, no validated response definitions for the SDAI and CDAI are available. OBJECTIVE: The authors aimed to define minor, moderate and major response criteria for the SDAI. METHODS: The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by κ statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD). RESULTS: Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses. CONCLUSION: These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.
23179004 Same-day or historical ESR for disease activity score measurement: does it matter? 2013 Feb Several guidelines recommended routine use of Disease Activity Score-28 (DAS28) to monitor disease and the response to treatment for rheumatoid arthritis (RA). In practice, it may be appropriate to use historical erythrocyte sedimentation rate (ESR) values in place of same-day ESR, thereby preventing unnecessary delay in adjusting intervention. We asked whether ESR blood samples taken up to 3 months prior to the clinic appointment were adequate to accurately assess RA disease activity using the DAS28. RA patients (N = 66) who met the inclusion criteria were assessed at baseline and ESR obtained on the day of review to calculate the DAS28 and compared with the DAS28 derived from the latest previous ESR (mean interval, 38.6 days; range, 6-99 days). Limits of agreement (LoA) were used to assess the agreement between the DAS28 pairs. The mean age of the participants was 61.5 years (range, 20-83 years), with mean disease duration of 11.0 years (range, 0.1-40 years). Comparing the DAS28 using same-day ESR versus pre-recorded historical ESR showed a small statistical difference (mean, -0.09; 95 %CI, -0.1602 to -0.017) in the DAS28 score. The calculated LoA (-0.66 and 0.48) demonstrated acceptable agreement between DAS28 pairs, with 7.6 % of patients residing outside the LoA, all of whom had a significant treatment change. Disease misclassification occurred in 9.1 % of patients who were close to disease activity boundaries. Our results indicate that differences in the DAS28 due to a previous or same-day ESR are unlikely to be clinically significant for RA patients with established disease. A decision to adjust treatment therefore may be confidently made for most patients using the most recent ESR for calculating the DAS28, provided there was no major change in treatment since the last ESR measurement.
22915619 Rituximab dissociates the tight link between disease activity and joint damage in rheumato 2013 Jan BACKGROUND/OBJECTIVE: Progression of joint damage is linked to disease activity. This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate (MTX). It is hitherto unknown if this may also be true for therapies targeting B-cells. We thus evaluated if rituximab (RTX) therapy inhibits joint damage irrespective of its effects on disease activity. METHODS: We used a random 90% sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis (RA) receiving MTX (n=188) or MTX+RTX 1000 mg (n=204). Patients were divided into low, moderate and high disease activity at one year of treatment by simplified disease activity index (low disease activity (LDA), moderate disease activity (MDA), high disease activity (HDA)), or by swollen joint count (SJC) or C reactive protein (CRP) tertiles. Progression of damage by the Genant modified total Sharp score (TGSS) was compared between therapies (Kruskal-Wallis, Wilcoxon tests) for each of these subgroups. RESULTS: In patients treated with MTX, 1-year progression of TGSS In LDA, MDA and HDA was 0.40±0.88, 1.04±1.73, and 1.31±3.02, respectively. In contrast, on RTX+MTX, TGSS progression was 0.38±1.07, 0.39±1.28, and -0.05±0.44, respectively (for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group: p=0.003 and p=0.05, respectively). Additional analyses (tertiles of SJC, CRP, and matching for disease activity) confirmed the primary analysis. CONCLUSIONS: In early RA, progression of joint damage increases with increasing disease activity on MTX. RTX plus MTX retards damage independently of its effects on disease activity, since even in HDA destruction is halted, contrasting MTX monotherapy. This indicates that beyond cytokine blockade (TNF- and IL-6 inhibitors), also cell-directed therapy (anti-CD20 antibody) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage.
23185038 Myocardial ischaemia without obstructive coronary artery disease in rheumatoid arthritis: 2013 Jan OBJECTIVE: RA is associated with increased cardiovascular events, reportedly to equal diabetes mellitus (DM). The presence of myocardial ischaemia was assessed in asymptomatic high-risk RA patients and compared with patients with DM and a healthy control group. METHODS: Eighteen consecutive non-diabetic RA patients without known cardiovascular disease who developed a new carotid atheromatic plaque during the last 3 years were matched 1:1 for traditional cardiovascular risk factors with asymptomatic type 2 DM patients and 1:2 with asymptomatic non-RA, non-DM control subjects. After dobutamine stress contrast echocardiography with wall-motion and perfusion evaluation, coronary angiography was performed in those with positive stress tests. RESULTS: Ischaemia by echocardiography was found in 67% of RA patients; this was significantly higher than controls (31%, P = 0.019) but comparable to those with DM (78%, P = 0.71). Angiography performed in eight consenting RA patients was normal in four, revealed non-flow-limiting coronary atheromatic lesions in two and significant lesions in two patients. RA patients with ischaemia had CRP serum levels significantly higher by six-fold compared with those with normal stress echocardiography. CONCLUSION: Asymptomatic RA patients may display myocardial ischaemia at similar levels to DM patients but with low prevalence of obstructive coronary artery disease. Microvascular abnormalities associated with increased inflammatory response may account for these findings. Their exact nature and significance require further evaluation.
22739991 Incidence of progressive multifocal leukoencephalopathy in patients with rheumatoid arthri 2012 Nov BACKGROUND: Cases of progressive multifocal leukoencephalopathy (PML), a rare but serious disease, have been reported in patients with rheumatoid arthritis (RA) in association with biological therapy, but little is known about the incidence of PML in patients with RA in the absence of treatment exposure. OBJECTIVE: To estimate the incidence rate of PML in patients with RA compared with the general population, with and without exposure to biological agents. METHODS: Patients with adult onset RA, exposure to biological agents and a diagnosis of PML from 1999 through 2009 were identified from national registries and linked using each Swedish resident's unique personal identification number. General population comparators matched on age, sex and county were also identified. Crude and age- and sex-standardised incidence rates (cases per 100 000 person-years) were calculated with 95% CI. RESULTS: 66 278 patients with RA and 286 949 general population comparators were included in the study. The incidence rate of PML in the overall RA population was 1.0 (95% CI 0.3 to 2.5) compared with 0.3 (95% CI 0.1 to 0.6) in the general population. The difference in incidence rate was 0.7 (95% CI -0.3 to 17). Among all patients exposed to biological agents, only one patient was diagnosed with PML. CONCLUSION: Data from this national population-based cohort study suggest that patients with RA may have an increased rate of PML compared with the general population.
21666230 Distinct ACPA fine specificities, formed under the influence of HLA shared epitope alleles 2011 Aug OBJECTIVES: Human leucocyte antigen shared epitope (SE) alleles are associated with joint destruction, the presence of anticitrullinated protein antibodies (ACPA) and the ACPA fine specificity repertoire in rheumatoid arthritis (RA). A large variation in joint destruction is seen within the ACPA-positive patient population, and it is conceivable that certain ACPA reactivities contribute to radiological damage. The authors investigated whether ACPA fine specificities, which are formed under the influence of SE alleles, associate with the extent of radiographic joint damage. METHODS: Antibodies recognising six citrullinated epitopes were determined in sera of 330 ACPA-positive RA patients genotyped for SE alleles. The association between SE alleles, ACPA fine specificity and radiographic joint damage was assessed using radiographic follow-up data. A second cohort of 154 RA patients with 5 and 10-year radiographic follow-up was used for replication. RESULTS: SE alleles predisposed to the recognition of certain citrullinated epitopes. However, none of the ACPA fine specificities studied influenced radiographic joint damage. Importantly, although SE alleles associated with radiographic damage in the total RA population, this association was no longer detectable after stratification for the presence of ACPA. CONCLUSIONS: SE alleles are instrumental in shaping the ACPA repertoire. However, ACPA fine specificities formed under the influence of SE alleles do not seem to affect joint destruction.
22187011 Different apoptotic responses of RA synoviocytes depending on different genotypes of the m 2012 Apr Mdm2 is an ubiquitin ligase, which binds p53 and blocks its function as a transcription factor in the pathway of apoptosis. Recently we have showed that the SNP mdm2 T309G has a protective effect of the minor allele in rheumatoid arthritis (RA). However, a functional impact on apoptosis by the different genotypes of the mdm2 SNP has not been investigated. Genomic DNA was obtained from 49 cell lines of synoviocytes derived from 49 patients with RA, and the mdm2 SNP309 was genotyped by polymerase chain reaction and restriction enzyme analysis. Seven cell lines were identified as homozygous for TT (major allele of mdm2 SNP309), and four as homozygous for GG (minor allele). All 11 cell lines were stimulated with 5 ng/ml of TNF alpha and 2.5 ng/ml of Il-1beta. After staining with propidium iodide (25 µg/ml) DNA fluorescence was measured with FACS; the rate of apoptosis was defined as the percentage of cells with a sub-2n DNA content (= less than haploid DNA-content). The cell-lines genotyped with mdm2 SNP 309TT showed a significantly different apoptosis rate in percent compared with GG for both conditions with stimulation (19.4 ± 3.6 vs. 26.9 ± 1.8; P = 0.02) and without stimulation by TNF alpha and Il-1beta (27.4 ± 8.8 vs. 43.9 ± 2.4; P = 0.0002). In the cell culture in vitro model RA synoviocytes homozygous for mdm2 SNP 309GG had a higher apoptotic activity compared to TT, possibly identifying a protective effect of the minor allele.
21442172 Tuberculin reaction is not attenuated in patients with rheumatoid arthritis living in a re 2012 May Tuberculin reactions in patients with immunocompromised conditions have been reported to be attenuated compared with healthy controls. In the case of rheumatoid arthritis (RA), several studies have reported conflicting results. We performed this study to evaluate the tuberculin reaction in patients with RA in a region with intermediate burden of tuberculosis. Eighty-one RA patients and 104 age- and sex-matched controls who underwent tuberculin skin test (TST) at Severance Hospital in Seoul, South Korea were reviewed. TST was carried out using the Mantoux method. Indurations larger than 10 mm were considered positive. Information about risk factors for latent tuberculosis infection was acquired. The mean age of the patients with RA was 48 ± 14 years, and the median disease duration was 9 (1-203) months. The mean DAS28 was 5.22 ± 0.13. The control group consisted of healthy living donors for liver transplantation and the patients with diseases not related with immunosuppression. BCG vaccination, close contact history with active tuberculosis, and history of pulmonary tuberculosis were not different between the two groups. The positive rate of TST (34.6% vs. 38.5%) and the median skin induration size (5 mm vs. 6 mm) of the two groups were similar. Medications and DAS28 were not associated with the TST result. The tuberculin reaction of patients with RA is not attenuated compared with that of controls in South Korea.
22959919 Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treat 2012 Oct 28 We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers. Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS. Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS. This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.
20473760 Cost-effectiveness treatment with Rituximab in patients with rheumatoid arthritis in real 2011 Nov The cost-effectiveness of treatments that have the potential to change the "natural history" of a chronic progressive disease has to be evaluated over the long term. Cost-effectiveness estimates have been based on the concept that, with treatment, patients will not progress to the next level(s) of disease severity or will take a longer time to progress, thus avoiding or delaying the high costs and low utility associated with more severe disease. This analysis focused on the use of Rituximab in treating patients with moderate to severe RA for whom at least one anti-TNFα blocking agent had failed. The aim of our study was to evaluate the cost-effectiveness in 32 patients with rheumatoid arthritis in therapy with a single infusion of Rituximab 1,000 mg given on days 1 and 15 of each month for 1 year. After 6 months of treatment, we observed for all 32 patients a total quality-adjusted life year (QALY) gained of 11,840 with an average of 0.37 QALY for a single patient, a treatment cost of euro 5,610 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 15,114. After 1 year of treatment, we observed data for 28 patients with a total QALY gained of 11,480 with an average of 0.41 QALY for a single patient, a treatment cost of euro 9,690 and a QALY/cost ICER (incremental cost-effectiveness ratio) of euro 23,696. The benefit of using Rituximab is cost-effectiveness with a QALY/gained under the acceptable threshold of euro 50,000 in our observational study. These are important data for discussion from the economic point of view when we choose a biologic therapy for rheumatoid arthritis in clinical practice.
22589262 Validity and reliability problems with patient global as a component of the ACR/EULAR remi 2012 Jun OBJECTIVE: To investigate what factors influence patient global health assessment (PtGlobal), and how those factors and the reliability of PtGlobal affect the rate, reliability, and validity of recently published American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria when used in clinical practice. METHODS: We examined consecutive patients with RA in clinical practice and identified 77 who met ACR/EULAR joint criteria for remission (≤ 1 swollen joint and ≤ 1 tender joint). We evaluated factors associated with a PtGlobal > 1, because a PtGlobal ≤ 1 defined ACR/EULAR remission in this group of patients who had already met ACR/EULAR joint criteria. RESULTS: Of the 77 patients examined, only 17 (22.1%) had PtGlobal ≤ 1 and thus fully satisfied ACR/EULAR criteria. A large proportion of patients not in remission by ACR/EULAR criteria had high PtGlobal related to noninflammatory issues, including low back pain, fatigue, and functional limitations, and a number of patients clustered in the range of PtGlobal > 1 and ≤ 2. However, the minimal detectable difference for PtGlobal was 2.3. In addition, compared with a PtGlobal severity score, a PtGlobal activity score was 3.3% less likely to be abnormal (> 1). CONCLUSION: Noninflammatory factors contribute to the level of PtGlobal and result in the exclusion of many patients who would otherwise be in "true" remission according to the ACR/EULAR definition. Reliability problems associated with PtGlobal can also result in misclassification, and may explain the observation of low longterm remission rates in RA. As currently constituted, the use of the ACR/EULAR remission criteria in clinical practice appears to be problematic.
21269575 Intentional etanercept use during pregnancy for maintenance of remission in rheumatoid art 2011 Jan OBJECTIVES: Rheumatoid arthritis is associated with an increased risk of adverse pregnancy outcomes. TNF inhibitors are effective in the treatment of signs and symptoms of the disease although their safety during pregnancy is debated. METHODS: Two cases of women with rheumatoid arthritis in complete remission of the disease with etanercept who decided to continue the therapy throughout their pregnancy are presented. A longitudinal evaluation of the disease activity showed a satisfactory control and good pregnancy outcomes were obtained. A flare of the disease after delivery was not observed. CONCLUSIONS: Etanercept seems to be safe during pregnancy and lactation. A good control of the activity of the disease was reported throughout the pregnancy and during puerperium, when a reactivation of rheumatoid arthritis is often observed.
21565901 'I'm hurting, I want to kill myself': rheumatoid arthritis flare is more than a high joint 2012 Jan OBJECTIVE: People with RA have episodes of worsening disease activity (flares) that prompt them to seek clinical review or medication change. This study explored patients' perspectives of flare that prompts them to seek medication review. METHODS: Fourteen focus groups across five countries comprised 67 RA patients. Transcripts were analysed by several researchers and a patient, using inductive thematic analysis. RESULTS: Patients use flare for five different scenarios, including flare that prompts medical help-seeking, where six themes were identified. In 'Symptoms and early warnings', pain is intense (wanting to die), constant and persistent and considered a key feature. Systemic features predominate, including fatigue, feeling generally ill (flu-like), physical and cognitive shut-down and social withdrawal. Warning signs (prodrome) comprise fatigue and flu-like symptoms. 'Self-management of intensifying symptoms' includes pacing, heat/cold, rest and increasing medication, often without medical advice. Patients 'Define this as uncontrollable flare' when clusters of unprovoked, persistent symptoms halt their ability to run daily life, until prompted into 'Seeking help when symptoms can't be contained'. Underpinning themes are 'Individual context' (e.g. different symptom clusters) and 'Uncertainty' (e.g. when to seek help). Patients report that the current patient global visual analogue scale (VAS) does not capture flare. CONCLUSION: Patients use flare for multiple events and seek help for complex clusterings of intense, unprovoked symptoms that defy self-management, not necessarily captured in joint counts or global VAS. Flare terminology and definition have implications for clinical practice and trials, therefore further research should establish a professional/patient consensus.
21976403 ¹H NMR-based metabolomic study of metabolic profiling for systemic lupus erythematosus. 2011 Nov Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multi-system involvement, diverse clinical presentation, and alterations in circulating metabolites. In this study, a (1)H NMR spectroscopy-based metabolomics approach was applied to establish a human SLE serum metabolic profile. Serum samples were obtained from patients with SLE (n = 64), patients with rheumatoid arthritis (RA) (n = 30) and healthy controls (n = 35). The NOESYPR1D spectrum combined with multi-variate pattern recognition analysis was used to cluster the groups and establish a disease-specific metabolites phenotype. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were capable of distinguishing SLE or RA patients from healthy subjects. The OPLS-DA model was able to predict diagnosis of SLE with a sensitivity rate of 60.9% and a specificity rate of 97.1%. For diagnosing RA, the model has much higher sensitivity (96.7%) and specificity (91.4%). The SLE serum samples were characterized by reduced concentrations of valine, tyrosine, phenylalanine, lysine, isoleucine, histidine, glutamine, alanine, citrate, creatinine, creatine, pyruvate, high-density lipoprotein, cholesterol, glycerol, formate and increased concentrations of N-acetyl glycoprotein, very low-density lipoprotein and low-density lipoprotein in comparison with the control population. The results not only indicated that serum NMR-based metabolomic methods had sufficient sensitivity and specificity to distinguish SLE and RA from healthy controls, but also have the potential to be developed into a clinically useful diagnostic tool, and could also contribute to a further understanding of disease mechanisms.
23466369 A novel kernel for correcting size bias in the logistic kernel machine test with an applic 2012 OBJECTIVES: The logistic kernel machine test (LKMT) is a testing procedure tailored towards high-dimensional genetic data. Its use in pathway analyses of case-control genome-wide association studies results from its computational efficiency and flexibility in incorporating additional information via the kernel. The kernel can be any positive definite function; unfortunately, its form strongly influences the test's power and bias. Most authors have recommended the use of a simple linear kernel. We demonstrate via a simulation that the probability of rejecting the null hypothesis of no association just by chance increases with the number of SNPs or genes in the pathway when applying a simple linear kernel. METHODS: We propose a novel kernel that includes an appropriate standardization in order to protect against any inflation of false positive results. Moreover, our novel kernel contains information on gene membership of SNPs in the pathway. RESULTS: When applying the novel kernel to data from the North American Rheumatoid Arthritis Consortium, we find that even this basic genomic structure can improve the ability of the LKMT to identify meaningful associations. We also demonstrate that the standardization effectively eliminates problems of size bias. CONCLUSION: We recommend the use of our standardized kernel and urge caution when using non-adjusted kernels in the LKMT to conduct pathway analyses.
21497537 Cartilage Oligomeric Matrix Protein (COMP) in systemic sclerosis (SSc): role in disease se 2012 Jan OBJECTIVE: The aim of the present study was to compare the serum level of COMP in both subsets of Systemic sclerosis (SSc) as a marker of arthritis and reveal an associated subclinical RA overlap and a relation to clinical, laboratory and radiological findings in SSc. METHODS: Forty adult SSc patients were included in the study and grouped into the two subsets diffuse (dSSc) and limited (lSSc) SSc. Their mean age was 40 ± 9 years. Thorough history taking and clinical examination were performed to all patients. Skin thickness was scored according to the modified Rodnan skin score method (MRSS). The disease activity was assessed by measuring the Medsger severity score. The joints were extensively examined and the tenderness counted according to the Ritchie articular index (RAI). Relevant laboratory and radiological investigations were carried out. The serum COMP level was determined by ELISA. RESULTS: The serum COMP was significantly higher in the SSc patients compared to the control and obviously higher in the dSSc compared to the lSSc patients. The level of COMP was higher in the females and significantly higher in the SSc patients with arthritis (56.5 ± 6.8 ug/ml) compared to those without (34 ± 8.3 ug/ml) (P 0.000). CONCLUSION: The COMP level may become a nonspecific but useful marker for joint involvement in SSc patients to identify patients at risk of joint damage and developing SSc-RA overlap syndrome even with mild arthritis.
21794797 [Manolo Hugué: from sculpture to painting due to arthritis]. 2011 Mar There are several artists that have suffered rheumatic diseases. Even then, they continued their creative activity. Paul Klee suffered from systemic sclerosis, Dufy and Renoir suffered from rheumatoid arthritis and Gaudí and Boticelli had systemic-onset juvenile idiopathic arthritis. The famous noucentism sculptor, Manolo Hugué, presented chronic polyarthritis that suggested rheumatoid arthritis. Although he underwent several treatments, such as hydrotherapy or diathermic therapy, he had to stop sculpting. Using the chisel was too painful for his hands. He began, then, painting and composing poetry.