Browse

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

ID PMID Title PublicationDate abstract
23644550 Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling-induced inf 2014 May OBJECTIVES: Hyperplasia of synovial fibroblasts, infiltration with lymphocytes and tissue hypoxia are major characteristics of rheumatoid arthritis (RA). Extensive data support a key role for toll-like receptors (TLRs) in RA. Little is known regarding the impact of hypoxia on TLR-induced inflammation in RA. The aim of this study was to reveal the effects of hypoxia and its regulator, hypoxia-inducible factor-1α (HIF-1α), on the inflammatory response of RA synovial fibroblasts (RASF) to TLR ligands. METHODS: Hypoxia was induced in RASF by incubation with Na2S2O4. TLR3 ligand polyIC, TLR2 ligand peptidoglycan, TLR4 ligand LPS and TLR9 ligand CpG were used to stimulate the cells. Effects of hypoxia on TLR-induced inflammatory mediators were determined by RT-PCR, qPCR and ELISA. Overexpression of HIF-1α as well as knocking-down its expression was used to reveal its fundamental role. RASF-induced inflammatory T cell expansion was determined by flow cytometry analysis of T helper (Th)1/Th17 cells, and IFN-γ/IL-17 production by ELISA after RASF/T cell coculture. RESULTS: Hypoxia potentiated the expression of inflammatory cytokines, metalloproteinases and VEGF in RASF stimulated by different TLR ligands, especially polyIC, a synthetic mimic of dsRNA from viruses or apoptotic cells. HIF-1α played a fundamental role in this synergy. Moreover, HIF-1α overexpression enhanced RASF-mediated expansion of inflammatory Th1 and Th17 cells, leading to proinflammatory IFN-γ and IL-17 production. CONCLUSIONS: Our findings suggest that hypoxia and HIF-1α may function in conjunction with TLR-stimulated innate immune responses to drive inflammation in RA. This pathway may serve as a therapeutic target for the disease.
24608963 Clinical and laboratory profiles of rhupus syndrome in a Chinese population: a single-cent 2014 Aug OBJECTIVE: The objective of this paper is to clarify the demographic, clinical and serologic characteristics of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome, known as 'rhupus syndrome'. METHODS: Between 1995 and 2012, 51 patients were classified as having rhupus among 3733 consecutive SLE patients. Rhupus was defined as a condition involving an overlap of RA and SLE features meeting the respective criteria of the American College of Rheumatology. The clinical and laboratory parameters of patients with rhupus syndrome were compared with those of 230 RA patients and 120 unselected SLE patients. RESULTS: The age at the onset of rhupus was significantly younger than that of RA (p < 0.05), but similar to that of SLE. The initial manifestation was arthritis in 84.3% (43/51) of rhupus patients. Symptoms of SLE manifested after an average of 9.2 years. SLE was the initial diagnosis in 7.8% (four of 51) of patients, whereas both diseases developed simultaneously in 7.8% of the patients. SLE-associated manifestations were mild in rhupus syndrome, particularly neurologic disorders. Haematopoietic involvement was the most prominent systemic manifestation in rhupus patients. CONCLUSION: Rhupus syndrome constitutes a subgroup of patients with distinct demographic, clinical and immunological characteristics. RA typically presents first, and less-severe SLE-associated damage is apparent.
23252949 Genetic risk factors for drug-induced liver injury in rheumatoid arthritis patients using 2013 Jan Low-dose methotrexate (MTX) is part of the mainstay of rheumatoid arthritis treatment. Hepatotoxicity is among the most feared side effects of low-dose MTX and is associated with increased morbidity. At present, histological evaluation of liver biopsies is the gold standard to retrospectively diagnose MTX-induced liver damage. Genetic markers present an interesting opportunity to preemptively identify patients at risk for MTX-induced hepatotoxicity. Here, we will review the literature on candidate genetic markers for the risk of MTX-induced hepatotoxicity. These candidate genetic markers include polymorphisms in the gene encoding the enzyme MTHFR.
25520183 Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options. 2015 Mar OBJECTIVE: Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. Citrullinations are the conversion of arginine to citrulline by peptidylarginine deiminase (PAD) enzymes, which affect protein properties. The aim of this review is to summarize the advances in citrullination research and further explore the potential of citrullination as a diagnostic tool as well as inhibition of PAD enzymes as a target for treatment. METHOD: We reviewed current literature with emphasis on the role of citrullination in health and disease, the nature of enzymes responsible for citrullination, and the potential of applying citrullinations in diagnostics and pharmaceuticals. CONCLUSION: Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. In RA measurement of anti-citrullinated protein antibodies (ACPA) against citrullinated protein fragments are widely used as a prognostic biomarker. More recently, it has been indicated that levels of selected citrullinated proteins carries additional potential as biomarkers. This includes citrullinated vimentin which provide prognostic information in diseases as fibrosis and ankylosing spondylitis. In addition, recent studies suggest that inhibition of PAD is a target for treatment of diseases such as RA and cancer where proteins that are citrullinated are believed to influence the disease activity.
24929185 The immune system, bone and RANKL. 2014 Nov 1 Bone and immune systems are tightly linked. In the past years, many molecules originally believed to belong to the immune system were found to function in bone cells. It is now evident that the two systems are coregulated by many shared cytokines and signaling molecules. Here we exemplify the complex interaction between bone metabolism and immune response focusing on the multifaceted role of receptor activator of NF-κB ligand (RANKL). RANKL is expressed by cells of both systems, is an essential regulator of bone degradation and exerts either pro or anti-inflammatory effects on the immune response. In the present review, we summarize the multiple functions of RANKL in bone and in the immune systems, aiming to provide an overview of the field of osteoimmunology.
25153613 In vivo kinematic analysis of posterior-stabilized total knee arthroplasty for the valgus 2014 Dec BACKGROUND: Most in vivo kinematic studies of total knee arthroplasty (TKA) report on the varus knee. The objective of the present study was to evaluate in vivo kinematics of a posterior-stabilized fixed-bearing TKA operated on a valgus knee during knee bending in weight-bearing (WB) and non-weight-bearing (NWB). METHODS: A total of sixteen valgus knees in 12 cases that underwent TKA with Scorpio NRG PS knee prosthesis and that were operated on using the gap balancing technique were evaluated. We evaluated the in vivo kinematics of the knee using fluoroscopy and femorotibial translation relative to the tibial tray using a 2-dimensional to 3-dimensional registration technique. RESULTS: The average flexion angle was 111.3°±7.5° in WB and 114.9° ± 8.4° in NWB. The femoral component demonstrated a mean external rotation of 5.9° ± 5.8° in WB and 7.4° ± 5.2° in NWB. In WB and NWB, the femoral component showed a medial pivot pattern from 0° to midflexion and a bicondylar rollback pattern from midflexion to full flexion. The medial condyle moved similarly in the WB condition and in the NWB condition. The lateral condyle moved posteriorly at a slightly earlier angle during the WB condition than during the NWB condition. CONCLUSIONS: We conclude that similar kinematics after TKA can be obtained with the gap balancing technique for the preoperative valgus deformity when compared to the kinematics of a normal knee, even though the magnitude of external rotation was small. LEVEL OF EVIDENCE: IV.
24429169 Antihomocitrullinated fibrinogen antibodies are specific to rheumatoid arthritis and frequ 2014 Feb OBJECTIVE: Anticitrullinated protein/peptide antibodies (ACPA) are implicated in rheumatoid arthritis (RA) pathogenesis and linked to the shared epitope (SE). Citrulline modification is very similar to a different modified amino acid, homocitrulline. We investigated antihomocitrullinated protein/ peptide antibody (AHCPA) specificity for RA, whether ACPA were also able to bind homocitrullinated targets, and whether the SE could accommodate homocitrullinated peptide. METHODS: Homocitrullinated fibrinogen was used to screen sera from patients with RA, psoriatic arthritis, and systemic lupus erythematosus, and healthy subjects for AHCPA using ELISA. Homocitrullination sites on fibrinogen were identified by mass spectrometry. ACPA were affinity-purified using a synthetic citrullinated peptide and tested for binding to homocitrullinated protein/peptide. Inhibition of antihomocitrullinated fibrinogen antibody binding was examined. Homocitrullinated peptide interaction with the SE was studied using computer modeling. RESULTS: IgG antihomocitrullinated fibrinogen antibodies were found specifically in 49% of patients with RA. Enrichment of ACPA by affinity purification from 5 patients with RA also enriched AHCPA. Serum AHCPA was inhibited by citrullinated fibrinogen and more significantly by homocitrullinated fibrinogen. Computer modeling indicated that the SE could accommodate a homocitrullinated peptide without steric hindrance. Mass spectrometry identified that 89/103 lysines of fibrinogen could be homocitrullinated, and 5 peptides that could be both citrullinated and homocitrullinated and are predicted to bind the SE. CONCLUSION: Antihomocitrullinated fibrinogen antibodies are specific to RA. The presence of AHCPA coincides with ACPA, and AHCPA copurifies with ACPA in affinity purification and is inhibited by citrullinated and homocitrullinated antigens. Thus AHCPA and ACPA are frequently cross-reactive and homocitrullinated proteins/peptides may bind the SE.
23724948 GEE for multinomial responses using a local odds ratios parameterization. 2013 Sep In this article, we propose a generalized estimating equations (GEE) approach for correlated ordinal or nominal multinomial responses using a local odds ratios parameterization. Our motivation lies upon observing that: (i) modeling the dependence between correlated multinomial responses via the local odds ratios is meaningful both for ordinal and nominal response scales and (ii) ordinary GEE methods might not ensure the joint existence of the estimates of the marginal regression parameters and of the dependence structure. To avoid (ii), we treat the so-called "working" association vector α as a "nuisance" parameter vector that defines the local odds ratios structure at the marginalized contingency tables after tabulating the responses without a covariate adjustment at each time pair. To estimate α and simultaneously approximate adequately possible underlying dependence structures, we employ the family of association models proposed by Goodman. In simulations, the parameter estimators with the proposed GEE method for a marginal cumulative probit model appear to be less biased and more efficient than those with the independence "working" model, especially for studies having time-varying covariates and strong correlation.
25502945 Genetics of neuroendocrine factors in rheumatoid arthritis. 2015 Jun Inadequate production of cortisol related to inflammation and decrease in adrenal androgen production are hallmarks of hypothalamic-pituitary-adrenal (HPA)-related endocrine findings in rheumatoid arthritis (RA). In particular, lower dehydroepiandrosterone sulfate (DHEAS) levels were consistently found in a subset of premenopausal RA females. Recently, several new gene variants have been identified in association with serum DHEAS concentrations, such as in SULT2A1 and HHEX genes. These DHEAS-related genes and other variants involved in HPA regulation may play a role in the adrenal androgen deficiency in RA. The aim of our study was to review involvement of genetic mechanisms of HPA regulation, with focus on adrenal androgens, in the context of RA pathophysiology. Although, effects of the DHEAS-related gene variants appear to be relatively small compared to other well-known factors such as age, complex interactions between DHEAS-associated genotypes and adrenal androgen hypofunction phenotype may exist in RA. Further studies analyzing specific neuroendocrine phenotype/genotype in RA are needed.
23893036 Observational study of optimization of biologic therapies in rheumatoid arthritis: a singl 2014 Aug To analyse the effectiveness of optimization of biologics in rheumatoid arthritis (RA). It was a single-centre retrospective observational study from January 2009 to September 2012. The effectiveness of the optimization of TNF antagonists, tocilizumab and abatacept in RA was studied. Optimization included predefined dose down-titration and/or expansion of dose interval in early arthritis with sustained DAS28-ESR <2.6 and established arthritis with a sustained DAS28-ESR <3.2. Primary outcome was time to relapse defined as increase in DAS28-ESR greater than 20 % over baseline. Cox's regression analysis was performed to identify predictors of relapse. Sixty-four patients were included in the study. In the survival analysis, rates of relapse were 9.8 % at 6 months, 31.4 % at 12 months and 44.6 % at 18 months. Rates of patients with an increase in DAS28-ESR > 20 % and ≥1 inflamed joint at 6, 9 and 18 months were 1.6, 17.2 and 27.1 %, respectively. In relapsing patients, mean DAS28-ESR at relapse was 3.44 (2.94-4.79) and mean DAS28-ESR following the return to the prior dose of the biologic was 2.52 (1.42-3.21). No predictors of relapse were found in multivariate analysis. Optimization of the treatment with biologics in RA is an efficacious and safe treatment option.
24405804 Rheumatoid arthritis and incident fracture in women: a case-control study. 2014 Jan 9 BACKGROUND: To examine fracture incidence in women with rheumatoid arthritis (RA) for an entire geographical region of south-eastern Australia. METHODS: Women aged 35 years and older, resident in the Barwon Statistical Division (BSD) and clinically diagnosed with RA 1994-2001 were eligible for inclusion as cases (n = 1,008). The control population (n = 172,422) comprised the entire female BSD population aged 35 years and older, excluding those individuals identified as cases. Incident fractures were extracted from the prospective Geelong Osteoporosis Study Fracture Grid. We calculated rate ratios (RR) and 95% confidence intervals (CI) to compare the age-adjusted rate of fracture between the RA and non-RA populations, and used a chi-square test to compare proportions of fractures between women with and without RA, and a two-sided Mann-Whitney U-test to examine age-differences. RESULTS: Among 1,008 women with RA, 19 (1.9%) sustained a fracture, compared to 1,981 fractures sustained by the 172,422 women without RA (1.2%). Fracture rates showed a trend for being greater among women diagnosed with RA (age-adjusted RR 1.43, 95%CI 0.98-2.09, p = 0.08). Women with RA sustained vertebral fractures at twice the expected frequency, whereas hip fractures were underrepresented in the RA population (p < 0.001). RA status was not associated with the likelihood of sustaining a fracture at sites adjacent to joints most commonly affected by RA (p = 0.22). CONCLUSION: Given that women with RA have a greater risk of fracture compared to women without RA, these patients may be a suitable target population for anti-resorptive agents; however, larger studies are warranted.
24961102 [Therapeutic efficacy of three bispecific antibodies on rheumatoid arthritis mice models]. 2014 Mar In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.
24962872 Relationship between radiographic joint space narrowing, sonographic cartilage thickness a 2015 Nov OBJECTIVE: To validate ultrasound (US) for measuring metacarpal cartilage thickness (MCT), by comparing it with anatomical measurement using cadaver specimens. To correlate US MCT with radiographic joint space narrowing (JSN) or width (JSW) in patients with rheumatoid arthritis (RA). METHODS: Bilateral metacarpophalangeal (MCP) joints of 35 consecutive outpatients, with recent hand X-rays, were included in the analysis. Metacarpal and phalangeal cartilage of MCP 2-5 was assessed bilaterally by US. JSW and JSN were evaluated on X-rays by the van der Heijde modified Sharp method (vdHS). In addition, cadaver specimens of MCP 2-5 joints (n=19) were evaluated by anatomical measurement and US. RESULTS: The agreement (intraclass correlation coefficient) between sonographic and anatomical MCT on cadaver specimens of MCP joints was 0.61. MCT of individual MCP joints correlated with individual MCP JSN (r=-0.32, p<0.001) and individual MCP JSW (r=0.72, p<0.001). No correlation was found between phalangeal cartilage thickness and JSN in individual MCP joints. The US MCT summary score for MCP joints 2-5 correlated with summary scores for JSW (r=0.78, p<0.001), JSN (r=-0.5, p<0.001), erosion score of the vdHS (r=-0.39, p<0.001) and total vdHS (r=-0.47, p<0.001). CONCLUSIONS: Sonographic cartilage assessment in MCPs is closely related to anatomical cartilage thickness. Both JSW and JSN by radiography represent cartilage thickness in the MCP joints of patients with RA quite well. Thus, US is a valid tool for measuring MCT if radiographs are not available or in case of joint malalignment.
24000379 Plasma from rheumatoid arthritis patients promotes pro-atherogenic cholesterol transport g 2013 Oct Immunologic derangements in rheumatoid arthritis (RA) patients likely contribute to premature atherosclerotic cardiovascular disease (CVD). Traditional CVD risk factors do not reliably identify at-risk RA patients, probably because disease-associated mechanisms are not taken into account. The purpose of this study was to determine whether plasma from subjects with RA exhibits atheroma-promoting properties leading to disruption of cholesterol homeostasis in human monocytes/macrophages. Twenty-one healthy controls (HC) and 22 RA patients were enrolled in an IRB approved study at Winthrop University Hospital. Naïve THP-1 macrophages were exposed to plasma from each HC and RA patient. Following incubation, RNA and protein were isolated. QRT-PCR and Western blotting techniques were then used to measure expression of proteins responsible for cholesterol efflux (ATP binding cassette transporter (ABC)A1, ABCG1, 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low density lipoprotein receptor (LOX)-1, CXCL16). To confirm the pro-atherogenic effects of RA plasma on macrophages, foam cell formation was quantified. Results showed that RA plasma downregulates cholesterol efflux proteins and upregulates scavenger receptors CD36, LOX1 and CXCL16. These pro-atherogenic changes in gene expression in the presence of RA plasma are associated with augmented lipid accumulation and foam cell formation by THP-1 macrophages. RA plasma induces macrophage cholesterol overload. Demonstration of disrupted cholesterol homeostasis mediated by RA plasma provides further evidence of the involvement of the immune system in atherogenesis. Our data suggest that chronic exposure to RA plasma adversely affects the capacity of monocytes/macrophages in the arterial wall to metabolize cholesterol and maintain lipid homeostasis, thereby contributing to the development of premature atherosclerosis.
23813577 Comorbidities are associated with poorer outcomes in community patients with rheumatoid ar 2013 Oct OBJECTIVE: To evaluate the impact of comorbidities on achieving remission by examining changes in the clinical disease activity index (CDAI) in RA patients in the community-based Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: A subcohort of 1548 RA subjects with varying disease duration met the following inclusion criteria: started a DMARD/biologic agent, continued therapy ≥ 3 months, CDAI ≥ 2.8 at study entry and followed longitudinally from baseline to follow-up (mean time 7.46 months). Patients reported comorbidities according to a standardized list of 33 conditions. Entry characteristics were compared across age categories using one-way analysis of variance. Linear and logistic regression models were constructed to assess characteristics [e.g. age, disease duration, number of previous DMARDs/biologics, baseline modified health assessment questionnaire (MHAQ), baseline CDAI and number of comorbidities] associated with primary outcomes: change in CDAI (baseline to follow-up) and CDAI remission (yes/no). RESULTS: Although disease activity measures at entry were similar across age categories, older patients had more comorbidities, less improvement in CDAI/MHAQ and were less likely to attain remission at follow-up. However, after adjusting covariates an increasing number of patient-reported comorbidities and higher baseline CDAI (but not age) were consistently and independently associated with a lower likelihood of clinical improvement or remission (P < 0.001). CONCLUSION: In this observational cohort of community RA patients an increasing number of patients reported comorbidities, independently correlated with less CDAI improvement over time. These results reaffirm that comorbidities may be an important factor in consideration of treat-to-target recommendations and aid in understanding achievable RA therapeutic goals.
23263548 The effects of fenofibrate on inflammation and cardiovascular markers in patients with act 2013 Dec Peroxisome proliferator-activated receptors α (PPARα) agonists, or fibrates, are used in the treatment for dyslipidemia. Experimental data suggest that fibrates have anti-inflammatory properties, and PPARα is essential for the differentiation of endothelial progenitor cells (EPC) which diminished pool in rheumatoid arthritis (RA) contributes to accelerated atherosclerosis. The data on fibrates' effects in patients with RA are limited. The aim of this study was to investigate changes in disease activity, inflammatory markers, lipid profile, and circulating EPC in active RA patients treated with fenofibrate. Twenty-seven patients with active RA taking traditional disease-modifying antirheumatic drugs (DMARDs) were prescribed fenofibrate (145 mg/day) for 3 months. All patients received background traditional DMARDs in stable doses. The outcomes measured were clinical disease activity variables, circulating cytokines, adipokines, lipids, and EPC. Twenty-five patients completed the study. At the end of treatment, there was a significant reduction in DAS28, all individual DAS28 components except tender joint count, the duration of morning stiffness, and in the patient's assessment of disease activity. Fifteen (60 %) patients achieved good/moderate EULAR response, while 10 (40 %) patients satisfied ACR20 response criteria. Treatment with fenofibrate resulted in significant decrease in CRP and IL-6 concentrations and improvement in lipid profile. There was no change in the concentrations of circulating EPC. In conclusion, fenofibrate treatment is associated with reduced inflammation and improved lipid profile in RA patients. Large randomized controlled studies are needed to confirm these results and to define the role of fibrates in the treatment for RA.
24200274 Risk of tuberculosis in rheumatoid arthritis patients on tumour necrosis factor-alpha inhi 2013 Dec OBJECTIVES: To quantify the incidence of tuberculosis (TB) in rheumatoid arthritis patients undergoing treatment with tumour necrosis factor-alpha inhibitors (TNFi). DESIGN: In a retrospective cohort study conducted using data from Taiwan's National Health Insurance claims databases, rheumatoid arthritis patients notified during the period 2006-2008 were recruited and classified based on types of TNFi treatment received. Active TB was the primary outcome. TB risk was estimated using Cox's proportional hazard model. The TB screening rate within 30 days of initiating treatment with TNFi was examined. RESULTS: Respectively 5079 and 829 patients were included in the non-TNFi and TNFi groups. Active TB rates were respectively 1411.3 and 679.5 events per 100,000 person-years in patients treated with adalimumab and etanercept. Significant TB risk was noted in patients treated with TNFi (aHR 4.87, 95%CI 2.14-11.06). No significant difference in active TB was observed between the TNFi subgroups (etanercept as reference, aHR 1.89, 95%CI 0.40-6.04). Only 8.7% (n = 9) of TNFi users underwent screening for TB before the first dose of TNFi. CONCLUSIONS: Patients on TNFi have a significantly greater risk of active TB than non-TNFi patients in the Taiwanese population. No difference in TB risk between the two available TNFi groups was noted. Screening for TB before initiating treatment with TNFi should be implemented.
25488101 Computer-aided and manual quantifications of MRI synovitis, bone marrow edema-like lesions 2015 Apr PURPOSE: To investigate the reliability and validity of computer-aided automated and manual quantification as well as semiquantitative analysis for MRI synovitis, bone marrow edema-like lesions, erosion and cartilage loss of the wrist in rheumatoid arthritis (RA) compared to the OMERACT-RAMRIS. METHODS AND MATERIALS: Wrist MRI was performed at 3 T in 16 patients with RA. Synovial volume and perfusion, bone marrow edema-like lesion (BMEL) volume, signal intensity and perfusion, and erosion dimensions were measured manually and using an in-house-developed automated software algorithm; findings were correlated with the OMERAC-RAMRIS gradings. In addition, a semiquantitative MRI cartilage loss score system was developed. Intraclass correlation coefficients (ICCs) were used to test the reproducibility of these quantitative and semiquantitative techniques. Spearman correlation coefficients were calculated between lesion quantifications and RAMRIS and between the MRI cartilage score and radiographic Sharp van der Heijde joint space narrowing scores. RESULTS: The intra- and interobserver ICCs were excellent for synovial, BMEL and erosion quantifications and cartilage loss grading (all >0.89). The synovial volume, BMEL volume and signal intensity, and erosion dimensions were significantly correlated with the corresponding RAMRIS (r = 0.727 to 0.900, p < 0.05). Synovial perfusion parameter maximum enhancement (Emax) was significantly correlated with synovitis RAMRIS (r = 0.798). BMEL perfusion parameters were not correlated with the RAMRIS BME score. Cartilage loss gradings from MRI were significantly correlated with the Sharp joint space narrowing scores (r = 0.635, p = 0.008). CONCLUSION: The computer-aided, manual and semiquantitative methods presented in this study can be used to evaluate MRI pathologies in RA with excellent reproducibility. Significant correlations with standard RAMRIS were found in the measurements using these methods.
23465306 Transthyretin as a potential serological marker for the diagnosis of patients with early r 2013 May OBJECTIVES: To investigate the serum levels and modifications of transthyretin (TTR) in patients with rheumatoid arthritis (RA) by mass spectrometry, and the potential role of TTR in early RA. METHODS: Serum samples were collected from early RA (ERA), middle and late RA (LRA), osteoarthritis (OA) patients, and healthy controls (HC). Levels of TTR were measured by ELISA, and serum TTR was further detected by Western blot. A subsequent MALDI-TOF-MS was performed to analyse the modified TTR. RESULTS: Serum TTR levels in ERA (502.46±108.15 mg/l) was significantly higher than that of healthy controls (424.98±117.63 mg/l) (p<0.05). TTR levels in LRA was higher than that of HC but without statistical significance (p>0.05), and no statistical significance between OA (363.90±105.21mg/l) and HC (p>0.05). Two protein bands were identified corresponding to monomer and dimmer TTR by western blot. The proportion of TTR monomer was similar in each group. However, the proportion of TTR dimer in RA was lower than that in HC, which was decreased more in LRA (p<0.05). By MALDI-TOF-MS, four major peaks were observed in sera corresponding to native TTR (13749.86±1.48 m/z), Sul-TTR (13829.63±2.76 m/z), Cys-TTR (13870.70±2.70 m/z), and Cysgly-TTR (13927±5.77 m/z). The proportion of modified TTR varied with different disease stages. CONCLUSIONS: TTR levels in sera of patients with early RA were significantly increased. Four modified TTR were identified by MALDI-TOF-MS, and the proportion of modified TTR varied with different disease stages. Thus serum TTR could be considered as a potential serological marker for early diagnosis of RA.
23126558 Anti-cyclic citrullinated peptide antibodies: a comparison of different assays for the dia 2013 OBJECTIVES: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific markers of rheumatoid arthritis (RA). Considering the heterogeneity of the target antigens involved, and the test platforms and conjugates proposed in commercial anti-CCP assays, we assessed the diagnostic performances of four fully automated anti-CCP assays in a cohort of patients with RA compared to patients with other autoimmune and inflammatory disorders. We also evaluated the agreement between the qualitative results of these immunoassays. METHOD: We evaluated three anti-CCP2 assays [Eurodiagnostica enzyme-linked immunosorbent assay (ELISA), Elecsys electrochemiluminescence immunoassay (ECLIA) on the Modular E170 Analyzer, and Zenit chemiluminescence immunoassay (CLIA) on the Zenit RA Analyzer] and one anti-CCP3 assay (Inova ELISA). ELISAs were performed on an automated workstation. Samples from 112 patients with RA and a disease control group of 136 patients (53 with autoimmune diseases, 65 non-autoimmune disorders, and 18 infectious diseases) were studied (included 161 samples submitted consecutively to the laboratory). RESULTS: At a fixed specificity of 92%, the anti-CCP3 assay presented the highest sensitivity (75%) compared to the anti-CCP2 assays evaluated (63-72%). The Zenit anti-CCP2 assay gave the most false-positive results (especially in patients with viral infections and connective tissue diseases). The agreement between assays ranged from 86.3% to 95.2% and Kappa coefficients ranged from 0.724 to 0.899. CONCLUSIONS: Recently released automated workstations provide a valuable alternative to ELISA to diagnose RA. However, differences in diagnostic performances are highlighted in our experience, especially for the Zenit assay. In our cohort, the anti-CCP3 assay gave slightly better performances than the anti-CCP2 assays (with the exception of the Zenit assay).