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ID PMID Title PublicationDate abstract
20980283 The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and 2011 Jan BACKGROUND: Increased expression of type I IFN genes, also referred to as an IFN signature, has been detected in various autoimmune diseases including rheumatoid arthritis (RA). Interferon regulatory factors, such as IRF5, coordinate type I IFN expression. Multiple IRF5 variants were suggested as autoimmunity susceptibility factors. OBJECTIVE: As the linkage proof remains important to establish fully any genetic RA susceptibility factor, the authors took advantage of the largest reported European trio family resource dedicated to RA to test for linkage IRF5 and performed a genotype-phenotype analysis. METHODS: 1140 European Caucasian individuals from 380 RA trio families were genotyped for IRF5 rs3757385, rs2004640 and rs10954213 single nucleotide polymorphisms (SNP). RESULTS: Single marker analysis provided linkage evidence for each IRF5 SNP investigated. IRF5 linked to RA with two haplotypes: the CTA risk haplotype 'R' (transmission (T)=60.6%, p=23.1×10(-5)) and the AGG protective haplotype 'P' (T=39.6%, p=0.0015). Linkage was significantly stronger in non-erosive disease for both IRF5 R and P haplotypes (T=73.9%, p=4.20×10(-5) and T=19.6%, p=3.66×10(-5), respectively). Multivariate logistic regression analysis found IRF5 linked to RA independently of the rheumatoid factor status. IRF5 RR and PP haplotypic genotypes were associated with RA, restricted to the non-erosive phenotype: p=1.68×10(-4), OR 4.80, 95% CI 2.06 to 11.19; p=0.003, OR 0.17, 95% CI 0.05 to 0.57, respectively. CONCLUSION: This study provides the 'association and linkage proof' establishing IRF5 as a RA susceptibility gene and the identification of a genetic factor that seems to contribute to the modulation of the erosive phenotype. Further studies are warranted to clarify the role of IRF5 in RA and its subphenotypes.
23232804 Analysis of critical molecules and signaling pathways in osteoarthritis and rheumatoid art 2013 Feb Osteoarthritis (OA) and rheumatoid arthritis (RA) are the most prevalent forms of arthritis in the elderly. This study aimed to explore the molecular mechanisms of these diseases and identify underlying therapeutic targets. Using GSE1919 microarray data sets downloaded from the Gene Expression Omnibus database, we screened differentially expressed genes (DEGs) in OA and RA cells. The underlying molecular mechanisms of these crucial genes were investigated by Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Small molecule expression and SNP analysis were also conducted by searching CMap and dbSNP databases. More than 320 genes changed in the arthritic cells and there were only 196 DEGs between OA and RA. OA and RA activated the classic mitogen-activated protein kinase signaling pathway, insulin signaling pathway, antigen processing and presentation and intestinal immune network for IgA production. Graft-versus-host disease and autoimmune thyroid disease-related pathways were also activated in OA and RA. Parthenolide and alsterpaullone may be treatments for OA and RA and insulin-like growth factor 1, collagen α2(I) chain and special AT-rich sequence-binding protein 2 may be critical SNP molecules in arthritis. Our findings shed new light on the common molecular mechanisms of OA and RA and may provide theoretical support for further clinical therapeutic studies.
22433765 Quality-adjusted life expectancies in patients with rheumatoid arthritis--comparison of in 2012 Mar BACKGROUND: The aim of this study was to compare quality-adjusted life expectancy (QALE) for patients with rheumatoid arthritis generated from three generic health-related quality-of-life instruments. METHODS: Patients from 11 Danish rheumatology outpatient clinics were asked to report current health status using the EuroQol five-dimensional questionnaire (EQ-5D), 15D, and six-dimensional health state short form (derived from SF-12) (SF-6D) instruments. Clinical staff provided data on current disease status (C-reactive protein and Disease Activity Score that involves clinical assessment of 28 joints). National mortality data were retrieved from Statistics Denmark. For each of the three instruments, mean index scores were estimated by gender and 5-year age groups. Partial QALE was estimated for the age interval 30 to 79 years for different subsamples. RESULTS: Although the three quality-of-life index scores were highly correlated, there were statistically significant differences between the average index scores from the three instruments. The 15D provided the highest index score and SF-6D the lowest score. For a 30-year-old patient, the partial QALE ranged from 37.9 quality-adjusted life-years using the SF-6D to 45.6 quality-adjusted life-years using the 15D. The QALE for men and women differed by 6.2%, 4.0%, and 5.3% when the calculation was based on EQ-5D, SF-6D, and 15D index scores, respectively. The largest differences were observed when patients were grouped by functional status (Health Assessment Questionnaire score), where the EQ-5D showed a 50% difference in index score between the best and worst functional group while the SF-6D and 15D showed smaller differences (32% and 14%, respectively). DISCUSSION: This analysis has shown the difference in QALE estimates related to different instruments. The study emphasizes that unless outcome studies use the same instruments and scoring algorithms, the results will not be directly comparable.
22234706 Causes of a painful total knee arthroplasty. Are patients still receiving total knee arthr 2012 Jun PURPOSE: Whilst patients undergoing total knee replacements generally have good relief of their symptoms, up to 20% complain of persisting pain. Revision rates have therefore been rising, particularly so for unexplained pain. We reviewed the causes of painful total knee replacements including extrinsic causes. METHODS: Forty-five consecutive patients referred to our department with painful total knee replacement were reviewed with our standard protocol, including history and examination, inflammatory markers and radiological studies including radiographs of the hip and knee and computed tomography scan of the knee joint. RESULTS: Of the 45 patients, 15 patients had degenerative hip and lumbar spine disease which resolved after injections of the relevant joints. Nine patients had unexplained pain. CONCLUSIONS: Patients may still be undergoing knee arthroplasty for degenerative lumbar spine and hip osteoarthritis. We suggest heightened awareness at pre- and post-operative assessment and thorough history and examination with the use of diagnostic injections to identify the cause of pain if there is doubt.
22992002 The effect of anti-TNF-α vs. DMARDs on fatigue in rheumatoid arthritis patients. 2013 OBJECTIVES: Fatigue is experienced frequently by patients with rheumatoid arthritis (RA). Fatigue may be caused by high levels of pain and disease activity in RA but can remain present while disease activity is moderate to low. It is not clear whether RA patients receiving anti-tumour necrosis factor (TNF) treatment reach lower levels of acute fatigue than RA patients receiving disease-modifying anti-rheumatic drug (DMARD) treatment. The aim of our study was to analyse whether, in patients with RA, the effect of anti-TNF on fatigue is greater than the effect of DMARD treatment. METHOD: Sixty-seven RA patients receiving anti-TNF treatment and 104 RA patients receiving DMARDs were included. All patients were on stable treatment for at least 6 months prior to baseline measurement. Fatigue was measured monthly over 1 year with the fatigue severity subscale of the Checklist Individual Strength (CIS-fatigue). The association between persistent severe fatigue and medication group was analysed using multiple linear regression including confounders. RESULTS: In the anti-TNF group the mean (SD) level of persistent fatigue was significantly higher than in the DMARD group [32.2 (11.4) vs. 28.3 (10.9), p = 0.025] and more patients experienced persistent severe (CIS-fatigue score ≥ 35) fatigue (42% and 27% respectively, p = 0.043). However, when correcting for age, disease activity, haemoglobin, treatment duration, pain, physical disability, and clinical depression, medication type seemed to influence neither the mean level of persistent fatigue (p = 0.251) nor the percentage of patients with persistent severe fatigue (p = 0.745). CONCLUSIONS: When taking into account probable confounders including disease activity, medication type did not influence persistent fatigue in RA patients. It seems that, besides its anti-inflammatory effect, anti-TNF has no complementary effect on persistent fatigue.
22853635 Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arth 2012 Aug 1 BACKGROUND: Rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed. METHODS: Data on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women. RESULTS: In total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis). Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse) scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse) scores for objective disease activity measures. A similar trend to RA was seen in IBD. CONCLUSIONS: Women with RA or psoriasis scored significantly higher on subjective, but not on objective, disease activity measures than men, and the same trend was seen in IBD. This indicates that at the same level of treatment, the disease has a greater effect in women. These findings might suggest that in all three diseases, subjective measures are discounted to some extent in the therapeutic decision-making process, which could indicate undertreatment in female patients.
22511483 Long-term followup for rheumatoid arthritis patients in a multicenter outcomes study of si 2012 Sep OBJECTIVE: Rheumatoid arthritis (RA) often results in deformities at the metacarpophalangeal (MCP) joints. Patients with severe deformities can be treated by silicone metacarpophalangeal joint arthroplasty (SMPA). The objective of the study is to prospectively compare long-term outcomes for an SMPA surgical and a nonsurgical cohort of RA patients. METHODS: A total of 67 surgical and 95 nonsurgical patients with severe subluxation and/or ulnar drift of the fingers at the MCP joints were recruited from 2004-2008 in this multicenter prospective cohort study. Patients could elect to undergo SMPA or not. Outcomes included the Michigan Hand Outcomes Questionnaire (MHQ), Arthritis Impact Measurement Scales 2 (AIMS2), grip/pinch strength, Jebsen-Taylor Test, ulnar deviation, extensor lag, and arc of motion measurements at the MCP joints. RESULTS: There was no significant difference in the mean age, race, education, and income at baseline between the 2 groups. Surgical subjects had worse MHQ function and functional measurements at baseline. At 3 years, the mean overall MHQ score and the MHQ function, activities of daily living, aesthetics, and satisfaction scores showed significant improvement in the surgical group compared to the nonsurgical group. Ulnar deviation, extensor lag, and arc of motion in the MCP and proximal interphalangeal joints also improved significantly in the surgical group. No improvement was seen in the mean AIMS2 scores and grip/pinch strength. Complications were minimal with a fracture rate of 9.5%. CONCLUSION: RA patients with poor baseline functioning showed long-term improvement in hand function and appearance following treatment with SMPA compared to nonsurgical controls.
23247460 [Characteristics of vascular morphology and vascular endothelial growth factor in patients 2012 Dec 18 OBJECTIVE: To study the differences in vascular morphology and vascular endothelial growth factor (VEGF) of early knee osteoarthritis and rheumatoid arthritis and to evaluate whether VEGF mRNA and VEGF protein expression correlate with disease activity and vascular morphology. METHODS: VEGF mRNA and VEGF protein in OA and RA synovium were detected by means of in situ hybridization and immunohistochemistry. Vascular morphology was assessed by arthroscopy. The level of VEGF protein expression of synovium was evaluated to make sure whether it was correlated with disease activity and macroscopic observation by arthroscopy. RESULTS: Significant differences of VEGF mRNA and protein expression were found in synovium lining layer region, perivascular region and sub-lining region between OA and RA. The correlations were found between VEGF expression in sub-lining region and erythrocyte sedimentation rate (ESR) in OA, in synovium lining layer and the counts of platelet in RA, in sub-lining region and C-reaction protein (CRP) in RA. The correlation was found between VEGF expression and synovium lining layer, between VEGF expression and synovial hypertrophy in sub-lining region in OA; The expression of VEGF in synovium lining layer in RA demonstrated its correlation with vascular morphology, tortuous vessels, and vascular density. CONCLUSION: There is differential VEGF mRNA/VEGF protein expression between OA and RA in each layer of synovial membrane. This phenomenon may be responsible for the pathogenic mechanisms of osteoarthritis and rheumatoid arthritis.
22691272 Investigation of the role of endosomal Toll-like receptors in murine collagen-induced arth 2012 Jun 12 INTRODUCTION: Endosomal toll-like receptors (TLRs) have recently emerged as potential contributors to the inflammation observed in human and rodent models of rheumatoid arthritis (RA). This study aims to evaluate the role of endosomal TLRs and in particular TLR7 in the murine collagen induced arthritis (CIA) model. METHODS: CIA was induced by injection of collagen in complete Freund's adjuvant. To investigate the effect of endosomal TLRs in the CIA model, mianserin was administered daily from the day of disease onset. The specific role of TLR7 was examined by inducing CIA in TLR7-deficient mice. Disease progression was assessed by measuring clinical score, paw swelling, serum anti-collagen antibodies histological parameters, cytokine production and the percentage of T regulatory (Treg) cells. RESULTS: Therapeutic administration of mianserin to arthritic animals demonstrated a highly protective effect on paw swelling and joint destruction. TLR7-/- mice developed a mild arthritis, where the clinical score and paw swelling were significantly compromised in comparison to the control group. The amelioration of arthritis by mianserin and TLR7 deficiency both corresponded with a reduction in IL-17 responses, histological and clinical scores, and paw swelling. CONCLUSIONS: These data highlight the potential role for endosomal TLRs in the maintenance of inflammation in RA and support the concept of a role for TLR7 in experimental arthritis models. This study also illustrates the potential benefit that may be afforded by therapeutically inhibiting the endosomal TLRs in RA.
21885031 [Rheumatoid arthritis: a cardiovascular disease?]. 2012 Apr Mortality in rheumatoid arthritis (RA) is doubled when compared to the general population. This excess in mortality can be explained in half of cases by cardiovascular (CV) events. The risk of myocardial infarction is increased by about 60% in RA. Mortality secondary to cerebrovascular stroke is increased by 50% even if the incidence of stroke is not increased. Indeed, the risk of fatal CV events is increased in RA when compared to the general population. The increased CV risk cannot be explained only by traditional CV risk factors, even if smoking and changes in lipid profile may be implied. It is mainly related to the chronic inflammatory condition that causes many metabolic disturbances. Other parameters such as treatments used in RA also play a role. Thus, it is essential for proper management of RA patients to be aware of this risk and to treat any modifiable CV risk factors.
21905349 Recurrent intra-oral herpes simplex 1 infection. 2011 Jul Human herpes simplex 1 virus (HSV-1) is a DNA virus that has the ability to lie latent and be subsequently re-activated at any point during a patient's life. In the immunocompetent patient, resolution of clinical signs and symptoms usually occurs spontaneously after 14 days. In the immunocompromised patient, healing is often delayed and the effects are much more debilitating. Indications for therapeutic regimes of systemic antiviral treatment are discussed. CLINICAL RELEVANCE: Recurrent oral ulceration caused by HSV-1 may be seen by the general dental practitioner and can cause significant morbidity.
22269280 Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a 2012 Jan 24 BACKGROUND: While it is recognised that depression is prevalent in Rheumatoid Arthritis (RA), recent studies have also highlighted significant levels of anxiety in RA patients. This study compared two commonly used scales, the Depression Anxiety and Stress Scale (DASS) and the Hospital Anxiety and Depression Scale (HADS), in relation to their measurement range and cut points to consider the relative prevalence of both constructs, and if prevalence rates may be due to scale-specific case definition. METHODS: Patients meeting the criteria for RA were recruited in Leeds, UK and Sydney, Australia and asked to complete a survey that included both scales. The data was analysed using the Rasch measurement model. RESULTS: A total of 169 RA patients were assessed, with a repeat subsample, resulting in 323 cases for analysis. Both scales met Rasch model expectations. Using the 'possible+probable' cut point from the HADS, 58.3% had neither anxiety nor depression; 13.5% had anxiety only; 6.4% depression only and 21.8% had both 'possible+probable' anxiety and depression. Cut points for depression were comparable across the two scales while a lower cut point for anxiety in the DASS was required to equate prevalence. CONCLUSIONS: This study provides further support for high prevalence of depression and anxiety in RA. It also shows that while these two scales provide a good indication of possible depression and anxiety, the estimates of prevalence so derived could vary, particularly for anxiety. These findings are discussed in terms of comparisons across studies and selection of scales for clinical use.
23136555 The pathological and physiological roles of IL-6 amplifier activation. 2012 The NFκB-triggered positive feedback loop for IL-6 signaling in type 1 collagen+ non-immune cells (IL-6 amplifier) was first discovered to be a synergistic signal that is activated following IL-17A and IL-6 stimulation in type 1 collagen+ non-immune cells. Subsequent disease models have shown that it can also be stimulated by the simultaneous activation of NFκB and STAT3, functions as a local chemokine inducer, and acts as a mechanism for local inflammation, particularly chronic ones like rheumatoid arthritis and a multiple sclerosis. Moreover, we have recently shown that hyper activation of the IL-6 amplifier via regional neural activation establishes a gateway for immune cells including autoreactive T cells to pass the blood-brain barrier at dorsal vessels in 5(th) lumbar cord. Here we review how the IL-6 amplifier is activated by neural activation and the physiological relevance of the gateway to the central nervous system. Accumulating evidences continues to suggest that the IL-6 amplifier offers a potential molecular mechanism for the relationship between neural activation and the development of inflammatory diseases, which could establish a new interdisciplinary field that fuses neurology and immunology.
22911970 Iterative decomposition of water and fat with echo asymmetry and least-squares estimation 2013 Mar PURPOSE: To compare fat-suppressed magnetic resonance imaging (MRI) quality using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) with that using chemical shift selective fat-suppressed T1-weighted spin-echo (CHESS) images for evaluating rheumatoid arthritis (RA) lesions of the hand and finger at 3T. MATERIALS AND METHODS: MRI was performed in eight healthy volunteers and eight RA patients with a 3.0T MR system (Signa HDxt GE healthcare) using an eight-channel knee coil. FS-CHESS-T1-SE and IDEAL imaging were acquired in the coronal planes covering the entire structure of the bilateral hands with a slice thickness of 2 mm. In the RA patients both images were obtained after intravenous gadolinium administration. Image quality was evaluated on a five-point scale (1 = excellent to 5 = very poor). Synovitis and bone marrow contrast uptake on MR images were reviewed by two musculoskeletal radiologists using the Rheumatoid Arthritis MRI Scoring System (RAMRIS) of the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) group. RESULTS: IDEAL showed uniform FS unaffected by magnetic field inhomogeneity and challenging geometry of hand and fingers, while CHESS-T1-SE often showed FS failure within the first metacarpal joint, tip of the finger, and ulnar aspect of the wrist joint. Overall image quality was significantly better with IDEAL than CHESS-T1-SE images (4.43 vs. 3.43, P < 0.01). Interobserver agreement (κ value) for synovitis and bone marrow contrast uptake was good to excellent with IDEAL (0.74-0.91, 0.62-0.89, respectively). CONCLUSION: IDEAL could compensate for the effects of field inhomogeneities, providing uniform FS of the hand and finger than did the CHESS-T1-SE sequence.
22187055 The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on pati 2012 Dec Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (<12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.
23091349 Comprehensive evaluation of different T-helper cell subsets differentiation and function i 2012 Rheumatoid arthritis (RA) is the most common autoimmune disorder. Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. This study was to investigate Th1, Th2, Th17, and Treg differentiation and related cytokines in RA patients. The frequencies of Th1, Th2, Th17, and Treg cells in peripheral blood of RA patients (n = 76) and healthy controls (n = 18) were determined by flow cytometry. Eight serum cytokines were analyzed using cytometric bead array. The results demonstrated that RA patients exhibited increased peripheral Th1/Th17 cells and Th1/Th17-related cytokines. However, Th1 cells only reached significant difference at advanced stage, but Th17 at all stages, suggesting more important roles in Th17 cells. For Th2 and Treg cells, there was a different function pattern in RA progression. Although with the increase of DAS28 score, Th2 cell experienced some degree of decrease in RA patients, no significant difference was observed. IL-4 and IL-10 showed a significant increase in RA patients. These indicated that Th2 cells might exert immunosuppression effects mainly by secreting cytokines. Treg cells were found significantly decreased in RA patients, but no difference was observed in TGF-β expression, indicating a cell-cell interaction pattern in Treg cell.
21362759 High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occ 2011 Jun OBJECTIVE: To investigate whether levels of anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with rheumatoid arthritis (RA) are associated with the co-occurrence of lung diseases. METHODS: A total of 252 RA patients were included in a cross-sectional study. Pulmonary disease was confirmed by high-resolution chest computed tomography scan. Circulating anti-CCP2 were quantified using ELISA. Multivariate logistic regression was conducted to identify independent risk factors for lung disease. RESULTS: Male sex (OR 3.29, 95% CI 1.59-6.80) and high anti-CCP2 levels (OR 1.49, 95% CI 1.25-1.78) were identified as independent risk factors for lung disease in the RA population. CONCLUSION: High anti-CCP2 levels are associated with lung disease in the RA population.
23259628 IL-6 inhibition for the treatment of rheumatoid arthritis and other conditions. 2012 New data published or presented in the past year has expanded our understanding of the clinical use of interleukin 6 (IL-6) inhibitors and their role in the management of rheumatoid arthritis (RA) and other rheumatic diseases. Data has become available on the use of tocilizumab (TCZ) in comparison to adalimumab, as therapy in RA patients with an inadequate response to TNF inhibitors and on its role as monotherapy. Early data on the efficacy and safety of subcutaneously administered TCZ suggests a potential role for this formulation of the drug. Extension studies of the use of TCZ in systemic juvenile inflammatory arthritis have confirmed the long-term efficacy of the drug in this illness, while studies on the use of TCZ and other IL-6 inhibitors in spondyloarthropathies has been less encouraging. Finally, new agents targeting the IL-6 pathway have entered late stage clinical trials, and the early results are promising.
23000593 Discovery of serum proteomic biomarkers for prediction of response to infliximab (a monocl 2012 Dec 21 Biologics such as TNF antagonists are a new class of drugs that have greatly improved Rheumatoid Arthritis (RA) treatment. However, for unknown reasons, individual patients with RA respond to one of these drugs but not to others even those targeting the same molecule. Methods to predict response are sorely needed because these drugs are currently selected by trial and error, what is very inefficient and prejudicial for the patient and the healthcare system. Here, we have explored the discovery of protein biomarkers in serum from patients treated with infliximab, one of the major anti-TNF drugs. The study was based in a quantitative proteomics approach using 8-plex iTRAQ labeling. It combined depletion of the most abundant serum proteins, two-dimensional LC fractionation, protein identification and relative quantification with a hybrid Orbitrap mass spectrometer. This approach allowed the identification of 315 proteins of which 237 were confidently quantified with two or more peptides. The detection range covered up to 6 orders of magnitude including multiple proteins at the ng/mL level. A new set of putative biomarkers was identified comprising 14 proteins significantly more abundant in the non-responder patients. The differential proteins were enriched in apolipoproteins, components of the complement system and acute phase reactants. These results show the feasibility of this approach and provide a set of candidates for validation as biomarkers for the classification of RA patients before the beginning of treatment, so that anticipated non-responders could be treated with an alternative drug.
22927708 Serum levels of asymmetric dimethylarginine and apelin as potential markers of vascular en 2012 OBJECTIVES: Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetric-dimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. METHODS: We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. RESULTS: In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. CONCLUSIONS: ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.