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ID PMID Title PublicationDate abstract
21933639 Clinical significance of autoantibodies induced by infliximab treatment: two-year follow-u 2011 Infliximab is anti-TNFα monoclonal antibody, which is widely used in the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. Anti-TNFα treatment can induce the occurrence of autoantibodies but in the majority of treated patients, they have no clinical significance although several cases of drug induced lupus have been described. In our cohort of refractory RA patients treated with infliximab for one year, we found a very high number of patients who developed antinuclear autoantibodies (16 of 24 (66.6%) at the time of infliximab discontinuation) and anti-ds-DNA autoantibodies (12 of 24 (50%) at the time of infliximab discontinuation). However, in most of these patients they had no clinical significance. One patient developed clinical and laboratory signs of systemic lupus erythematosus (SLE), which over time became overt as SLE-RA overlapping unmasked by infliximab.
20821212 The balance between soluble receptors regulating IL-6 trans-signaling is predictive for th 2012 Jan The objective of this study is to investigate the relationship between soluble components of the interleukin 6 (IL-6) system mediating and modifying IL-6 trans-signaling and the RANKL-RANK-osteoprotegerin system in postmenopausal women with rheumatoid arthritis (RA). The following parameters were investigated in 126 postmenopausal women with RA: IL-6, soluble IL-6-receptor (sIL-6R), soluble glycoprotein 130 (sgp130), sRANKL, osteoprotegerin (OPG), osteocalcin, erythrocyte sedimentation rate and C-reactive protein in sera, pyridinolin and desoxypyridinolin crosslinks in the morning urine. Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (BMD-LS) and at the femoral neck (BMD-FN). Predictors of RANKL/OPG ratio and BMD were evaluated by multiple linear regression analysis. The following determinants of the RANKL/OPG ratio were identified: sIL-6R/sgp130 ratio and daily glucocorticoid (GC) dose as positive determinants in the whole group (R (2) = 0.56; P = 0.001), sIL-6R/sgp130 ratio as the exclusive positive determinant in patients with GC therapy (R (2) = 0.48; P = 0.001) and sgp130 as negative determinant in patients without GC (R (2) = 0.42; P = 0.031). Sgp130 was highly significantly positively correlated with OPG in the whole group (P < 0.001) as well as in patients with (n = 70; P < 0.05) and without GC therapy (n = 56; P < 0.01). sIL-6R was the main negative predictor of BMD-LS (R (2) = 0.41; P = 0.019). High sIL-6R/sgp130 ratio and/or low sgp130 are associated with a high sRANKL/OPG ratio in sera of postmenopausal women with RA indicating the critical significance of IL-6 trans-signaling for an increase in the RANKL/OPG ratio and of bone resorption. Inhibition of IL-6 trans-signaling may be an effective bone-protecting principle in postmenopausal women with RA.
22589380 Detection, scoring and volume assessment of bone erosions by ultrasonography in rheumatoid 2013 Apr OBJECTIVES: To determine the accuracy of ultrasonography (US) for bone erosion detection in different areas of rheumatoid arthritis (RA) metacarpophalangeal (MCP) joints with multislice CT as the reference method. Second, to establish the necessary bone volume loss on CT for US to reliably detect it as an erosion, and finally to compare two semiquantitative US-erosion scoring methods. METHODS: The 2nd-5th MCP joints of 49 patients with RA were examined by CT and US, and evaluated for the presence of bone erosion in each MCP joint quadrant. On CT, erosion volume was scored according to the OMERACT-RAMRIS score (bone volume loss in 10% increments of original bone volume). US erosions were scored 0-3 according to the Szkudlarek and Scoring by UltraSound Structural erosion (ScUSSe) systems, respectively. RESULTS: Seven hundred and eighty-four MCP joint quadrants were examined. Erosions were detected by CT in 259 quadrants and by US in 142 quadrants. Sensitivity/specificity/accuracy of US was overall 44%/95%/78% compared with 71%/95%/90% in areas with good US accessibility (radial 2nd MCP, ulnar 5th MCP and all dorsal/palmar aspects). US detected 95% of erosions with bone volume loss >20%. In US accessible areas, 63% of erosions with 1-10% bone volume loss and 94% of erosions with >10% bone loss were detected. The two US scoring systems agreed well on large erosions, whereas the smallest erosions (Szkudlarek grade 1, of which 86% were confirmed by CT) were not scored by ScUSSe. CONCLUSION: In accessible areas, US was highly accurate for detection and semiquantitative assessment of RA bone erosion. Even the smallest erosions, only detected in one plane, were generally confirmed by CT.
22652412 Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis. 2013 Feb Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test=anti-CCP/anti-CAP ratio>1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p=0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p=0.071) and C-reactive protein (p=0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.
22409930 Prognostic role of coronary calcification in patients with rheumatoid arthritis and system 2012 May OBJECTIVES: To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE). METHODS: A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events. RESULTS: Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events. CONCLUSIONS: Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.
21508506 Association of CD28 IVS3 +17T/C polymorphism with soluble CD28 in rheumatoid arthritis. 2011 OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology in which inflammatory pathology involves T cell activation and the CD28 costimulatory molecule involved in T cell presentation. The gene includes the CD28 IVS3 +17T/C polymorphism that could be associated with susceptibility to RA whereas the soluble concentrations of CD28 (sCD28) could be related to clinical activity. METHODS: We investigated the CD28 IVS3 +17T/C polymorphism in 200 RA patients and 200 healthy subjects (HS). Furthermore, we quantified the sCD28 concentrations in 77 samples of each group. We applied indexes focused to determine the activity and disability (DAS28 and Spanish HAQ-DI, respectively) in RA patients. RESULTS: RA patients had significantly higher frequencies of the CD28 T allele compared to HS (p = 0.032 OR = 1.59, C.I. 1.02-2.49). In addition, the IVS3 +17 T/T genotype frequency was also increased in RA vs. HS (p = 0.026). The RA patients showed higher sCD28 serum levels than HS (p = 0.001). Carriers of the T/T genotype in RA patients showed higher sCD28 levels than C/C carriers (p =0.047). In addition, a correlation between sCD28 and Spanish HAQ-DI (correlation, 0.272; p =0.016), was found. CONCLUSION: The T allele in CD28 IVS3 +17T/C polymorphism is associated with a susceptibility to RA in Western Mexico. In addition, increased sCD28 levels are related to T/T genotype in RA patients.
21484766 Dose escalation of certolizumab pegol from 200 mg to 400 mg every other week provides no a 2011 Aug OBJECTIVE: To determine whether certolizumab pegol (CZP) dosage escalation from 200 mg to 400 mg every other week benefits some patients with rheumatoid arthritis (RA). METHODS: In the extension of the Rheumatoid Arthritis Prevention of Structural Damage 1 (RAPID 1) study into an open-label study, all patients received CZP 400 mg every other week in combination with methotrexate (MTX). Before the open-label phase of the study, patients had received CZP 200 mg or 400 mg every other week, or placebo every other week, as add-on therapy to MTX. The open-label study included those who had completed the RAPID 1 study (to week 52) and also those who had been withdrawn from the study (at week 16, due to inadequate response). At 12 weeks and 48 weeks after enrollment in the open-label study, changes in the Disease Activity Score in 28 joints (DAS28) were compared in dose-escalation patients (200 mg increased to 400 mg every other week) versus stable-dosage patients (400 mg every other week), using cumulative probability plots of individual patient-level data. RESULTS: In the group of patients who had completed the RAPID 1 study and had moderate or severe disease activity at entry into the open-label study, and in those who had been withdrawn early from the RAPID 1 study, the median DAS28 improvements 12 weeks after enrollment into the open-label study were similar in the dose-escalation and stable-dose groups. Individual patient-level data revealed no greater likelihood of response in the group of patients who received an increased dosage of CZP versus those in whom a stable dosage was maintained, whether they had completed the RAPID 1 study or had been withdrawn early. CONCLUSION: Although patient heterogeneity in clinical settings is acknowledged, the present results indicate that increasing the dose of CZP from 200 mg to 400 mg offers little additional benefit in RA, even for selected patients.
22505696 Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9 2012 May OBJECTIVE: Genes or gene products associated with coronary artery disease in the general population were analyzed in rheumatoid arthritis (RA) patients with atherothrombotic manifestations (ATM). METHODS: A cross-sectional study of 681 individuals (498 women; 183 men) with RA (American College of Rheumatology criteria), a mean age of 60.6 ± 13.2 years, and mean disease duration of 15.5 ± 12.6 years who were consecutively recruited and followed for 6 years. The prevalence of ATM [i.e., myocardial infarction, angina pectoris with intervention, deep vein thrombosis/pulmonary embolism (DVT/PE), and/or stroke/transient ischemic attack (TIA)] was recorded. Polymorphisms were analyzed in the genes coding for growth differentiation factor 15 (GDF15)/monocyte inhibitory cytokine-1 (MIC-1; rs1058587), CD40 (rs1535045 and rs3765459), and the 9p21.3 locus (rs1333049). Controls were randomly selected (n = 687; matched for age and sex). RESULTS: The distribution of genotypes of GDF15/MIC-1 differed significantly between patients with RA and controls (chi-squared = 6.40, 2 df, p = 0.041). ATM were associated with polymorphism of the GDF15/MIC-1 G allele (OR 2.21, 95% CI 1.17-4.18), and with CC genotype of the 9p21.3 locus (rs1333049; OR 1.92, 95% CI 1.15-3.19). Stroke/TIA in women was associated with GDF15/MIC-1 GG genotype (OR 3.75, 95% CI 1.06-13.33), while stroke/TIA in men was associated with CD40 homozygous major alleles (OR 6.48, 95% CI 1.31-32.0 and OR 2.78, 95% CI 0.78-9.91, respectively). DVT/PE was associated with polymorphism in the GDF15/MIC-1 gene (rs1058587) minor allele (OR 3.53, 95% CI 1.30-9.58). CONCLUSION: The gene polymorphisms analyzed were associated with different ATM in RA. The GDF15/MIC-1 gene polymorphism was also associated with RA per se, suggesting a common etiology for RA and ATM.
21439786 Nucleic acid-stimulated antigen-presenting cells trigger T cells to induce disease in a ra 2011 May Autoimmune responses to heterogeneous nuclear ribonucleproteins (hnRNP) occur in many systemic autoimmune diseases, particularly in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. In RA, humoral and/or cellular autoimmunity to hnRNP-A2/B1 is the most prominent anti-nuclear reactivity, being detectable in more than 50% of patients. However, its pathogenic role has not been fully elucidated yet. Here, we report that splenocytes from rats with pristane-induced arthritis transfer disease after in vitro restimulation with hnRNP-A/B antigens. Remarkably, disease transfer can be blocked by nuclease treatment of hnRNPs and is also achieved with splenocytes stimulated with hnRNP-A/B associated DNA or RNA oligonucleotides (ON) alone. Induction of proinflammatory cytokines in splenocytes stimulated with hnRNP-A/Bs or ONs involves Toll-like receptors (TLR) 7 and 9 but not TLR3. Furthermore, although T cells are the main mediators of disease transfer they require restimulation with TLR-activated antigen-presenting cells such as macrophages in order to become arthritogenic. Thus, the autoantigenic properties of hnRNPs appear to be mediated by their associated nucleic acids binding to TLR7 and 9. Our data explain the specific selection of hnRNP-A2/B1 as autoantigen in RA and reveal the requirement of interaction between innate and adaptive immunity to initiate and drive inflammation in autoimmune arthritis.
22692876 Glucocorticoid-loaded core-cross-linked polymeric micelles with tailorable release kinetic 2012 Jul 16 Polymerizable and hydrolytically cleavable dexamethasone (DEX, red dot in picture) derivatives were covalently entrapped in core-cross-linked polymeric micelles that were prepared from a thermosensitive block copolymer (yellow and gray building block). By varying the oxidation degree of the thioether in the drug linker, the release rate of DEX could be controlled. The DEX-loaded micelles were used for efficient treatment of inflammatory arthritis in two animal models.
22378717 A systematic literature review of US definitions, scoring systems and validity according t 2012 Jul OBJECTIVE: To present the published data concerning the US assessment of tendon lesions as well as the US metric properties investigated in inflammatory arthritis. METHODS: A systematic literature search of PubMed, Embase and the Cochrane Library was performed. Selection criteria were original articles in the English language reporting US, Doppler, tenosynovitis and other tendon lesions in patients with RA and other inflammatory arthritis. Data extraction focused on the definition and quantification of US-detected tenosynovitis and other tendon abnormalities and the metric properties of US according to the OMERACT filter for evaluating the above tendon lesions. RESULTS: Thirty-three of 192 identified articles were included in the review. Most articles were case series (42%) or case-control (33%) studies describing hand and/or foot tenosynovitis in RA patients. The majority of older articles used only B-mode, whereas the most recent studies have incorporated Doppler mode. Definition of tenosynovitis or other tendon lesion was provided in 70% of the evaluated studies. Most of the studies (61%) used a binary score for evaluating tendon abnormalities. Concerning the OMERACT filter, 24 (73%) articles dealt with construct validity. The comparator most commonly used was clinical assessment and MRI. There were few studies assessing criterion validity. Some studies evaluated reliability (36%), responsiveness (21%) and feasibility (12%). CONCLUSION: US seems a promising tool for evaluating inflammatory tendon lesions. However, further validation is necessary for implementation in clinical practice and trials.
22451024 Inhibitory effects of simvastatin on migration and invasion of rheumatoid fibroblast-like 2013 Feb To investigate the effect of simvastatin on the migration and invasion of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and its cellular signal mechanisms, FLS from active RA patients were stimulated with 3 % FBS or GM-CSF in the presence or absence of simvastatin. Cells migration and invasion in vitro were measured by the Boyden chamber method. RhoA activity was assessed by a pull-down assay. Matrix metalloproteinases-2 (MMP-2) activity was evaluated by zymography. Simvastatin inhibits FBS- or GM-CSF-induced migration in a dose-dependent manner by RA FLS, and this inhibitory effect is independent of cell apoptosis. We also found that simvastatin suppressed in vitro invasion, adhesion, MMP-2 activity, cytoskeletal reorganization and RhoA activation. Furthermore, mevalonate or GGPP treatment reversed the inhibitory effect of simvastatin not only on migration and invasion in vitro but also on RhoA activation, and inhibition of RhoA by specific siRNA transfection reduced migration, adhesion and invasion of RA FLS. This study shows that simvastatin reduces RA FLS migration and invasion through the prevention of protein geranylgeranylation and RhoA activation. These findings provide a novel evidence that statin may be benefit for preventing RA arthritic destruction, and also indicate that RhoA may be a new target for the modulation of RA FLS migration and invasion.
22685273 Lessons for the use of non-biologic anchor treatments for rheumatoid arthritis in the era 2012 Jun Optimizing the use of key non-biologic drugs (MTX, prednisone) may prolong disease control, thereby delaying the need for costly biologic therapies. A number of lessons about the optimal use of therapy emerge from clinical studies. Clinical outcomes with non-biologic treatments, given early in the course of the disease, are as good as with biologic treatments. Combinations of treatments are usually required to achieve rapid and sustained remission. MTX remains an important anchor drug for RA therapy and should be given as soon as the diagnosis is made. As early disease control is important, the dose of MTX should be escalated rapidly to adequate levels. Tolerability of MTX is generally good relative to that of other alternative treatments. MTX (s.c.) may be considered if the response to oral MTX is inadequate or MTX is poorly tolerated. In addition to suppressing signs and symptoms of RA, glucocorticoids appear to have disease-modifying effects, at least in early RA. The disease-modifying effects of glucocorticoids probably persist after discontinuation of therapy. The risk of adverse effects of low-dose glucocorticoids is often overestimated. Administration of low-dose glucocorticoids in accordance with physiological circadian rhythms may bring efficacy and safety benefits. As a case in point, the CAMERA (Computer Assisted Management in Early Rheumatoid Arthritis) II study applied these lessons and has clearly shown the benefits of optimizing MTX and prednisone therapy.
21378402 Updated consensus statement on the use of rituximab in patients with rheumatoid arthritis. 2011 Jun BACKGROUND: Since initial approval for the treatment of rheumatoid arthritis (RA), rituximab has been evaluated in clinical trials involving various populations with RA. Information has also been gathered from registries. This report therefore updates the 2007 consensus document on the use of rituximab in the treatment of RA. METHODS: Preparation of this new document involved many international experts experienced in the treatment of RA. Following a meeting to agree upon the core agenda, a systematic literature review was undertaken to identify all relevant data. Data were then interrogated by a drafting committee, with subsequent review and discussion by a wider expert committee leading to the formulation of an updated consensus statement. These committees also included patients with RA. RESULTS: The new statement covers wide-ranging issues including the use of rituximab in earlier RA and impact on structural progression, and aspects particularly pertinent to rituximab such as co-medication, optimal dosage regimens, repeat treatment cycles and how to manage non-response. Biological therapy following rituximab usage is also addressed, and safety concerns including appropriate screening for hepatitis, immunoglobulin levels and infection risk. This consensus statement will support clinicians and inform patients when using B-cell depletion in the management of RA, providing up-to-date information and highlighting areas for further research. CONCLUSION: New therapeutic strategies and treatment options for RA, a chronic destructive and disabling disease, have expanded over recent years. These have been summarised in general strategic suggestions and specific management recommendations, emphasising the importance of expedient disease-modifying antirheumatic drug implementation and tight disease control. This consensus statement is in line with these fundamental principles of management.
22071859 Antidepressants for pain management in rheumatoid arthritis. 2011 Nov 9 BACKGROUND: Pain management is a high priority for patients with rheumatoid arthritis (RA). Antidepressants are sometimes used as adjuvant agents to enhance pain relief, help with sleep and reduce depression. Such antidepressants include tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), selective serotonin noradrenaline reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). However, the prescription of antidepressants in this population remains controversial because of conflicting scientific evidence. OBJECTIVES: The aim of this review was to determine the efficacy and safety of antidepressants in pain management in patients with RA. SEARCH METHODS: We performed a computer assisted search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, 4th quarter); MEDLINE (1950 to November Week 1, 2010); EMBASE (2010 Week 44); and PsycINFO (1806 to November Week 2, 2010). We also searched the 2008-2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) abstracts and performed a handsearch of reference lists of articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared an antidepressant therapy to another therapy (active or placebo, including non-pharmacological therapies) in adult patients with RA who had at least one clinically relevant outcome measure. Outcomes of interest were pain, adverse effects, function, sleep, depression and quality of life. DATA COLLECTION AND ANALYSIS: Two blinded review authors independently extracted data and assessed the risk of bias in the trials. We conducted meta-analyses to examine the efficacy of antidepressants on pain, depression and function, as well as their safety. MAIN RESULTS: We included eight RCTs (652 participants) in this review. All trials evaluated TCAs and two trials evaluated a SSRI as a comparator. Seven of the eight trials had high risk of bias. There was insufficient data for a number needed to treat for an additional beneficial outcome (NNTB) to be calculated for the primary outcome measure of pain. The qualitative analyses found no evidence of an effect of antidepressants on pain intensity or depression in the short-term (less than one week), and conflicting evidence of a medium- (one to six weeks) or long-term (more than six weeks) benefit. There were significantly more minor adverse events in patients receiving TCAs compared with those receiving a placebo (risk ratio (RR) 2.27, 95% confidence interval (CI) 1.17 to 4.42), but there was no significant increase in withdrawals due to an adverse event (RR 1.09, 95% CI 0.49 to 2.42). AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the routine prescription of antidepressants as analgesics in patients with RA as no reliable conclusions about their efficacy can be drawn from eight placebo RCTs. The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment. More high quality trials are needed in this area.
21794808 [The impact of therapy with TNF-blockers on health-related quality of life in rheumatoid a 2011 May INTRODUCTION: The aim of this pilot study was to evaluate the initial response to 16 weeks of treatment with infliximab and etanercept of disease activity and quality of life in a cohort of 37 patients with established rheumatoid arthritis. PATIENTS AND METHOD: Patients were selected from the Unit of Rheumatology in Hospital Clínico San Cecilio from Granada, refractory to conventional treatment with disease modifying antirheumatic drugs. To assess the disease activity, Disease activity score (DAS28) was used and the measurement of quality of life was evaluated with the Spanish version of the SF-36 Health Survey (SF-36) and the RA-specific questionnaire QoL Scale (Quality of Life in Rheumatoid Arthritis). RESULTS: Preliminary results show a significant decrease in inflammatory activity of the disease and consequently in HRQL scores. The comparison with the general reference population shows a deviation well below average, especially in the "physical function" dimension with a rising response pattern in all dimensions. The correlation between specific scores (QoL-RA scale) and generic ones (SF-36) for HQ-treatment also showed significance, especially with the physical aggregate. DISCUSSION: An important limitation of the present study is the number of patients and the duration of the treatment; despite this, improvements in functional parameters and quality of life are evident and remain roughly stable since the first weeks of treatment. This allow us to continue the study and increase the number of patients. CONCLUSIONS: The preliminary results obtained with TNF-blockers after 16 weeks of treatment in RA objectively show the effectiveness of these drugs and also the perception by the patients of the effect on their quality of life.
22274761 Focusing on plasma glycoprotein VI. 2012 Apr New methods for analysing both platelet and plasma forms of the platelet-specific collagen receptor, glycoprotein VI (GPVI) in experimental models or human clinical samples, and the development of the first therapeutic compounds based on dimeric soluble GPVI-Fc or anti-GPVI antibody-based constructs, coincide with increased understanding of the potential pathophysiological role of GPVI ligand binding and shedding. Platelet GPVI not only mediates platelet activation at the site of vascular injury where collagen is exposed, but is also implicated in the pathogenesis of other diseases, such as atherosclerosis and coagulopathy, rheumatoid arthritis and tumour metastasis. Here, we describe some of the critical mechanisms for generating soluble GPVI from platelets, and future avenues for exploiting this unique platelet-specific receptor for diagnosis and/or disease prevention.
22345652 Production of autoantibodies against citrullinated antigens/peptides by human B cells. 2012 Apr 1 Autoantibodies against citrullinated protein Ags (ACPA) are associated with the development of rheumatoid arthritis (RA). This immune response against citrullinated protein Ags, which is thought to be facilitated by certain MHC HLA-DR alleles, is highly specific for this disease and has been speculated to be involved in the pathogenesis. We have previously studied cultures of B cells for the production of Abs against HLA Ags. The aim of the current study was to examine the role of B cells in the production of ACPA in patients with RA. Peripheral blood B cells from RA patients and healthy people were cultured with EL4-B5, a murine cell line expressing human CD40L, and with T cell factors to stimulate the in vitro production of Abs by B cells isolated from peripheral blood. ACPA were produced by cultured B cells from RA patients, as determined by reactivity to cyclic citrullinated peptide (CCP). The results showed that 22% of the healthy persons tested also had B cells that could produce ACPA. Patients with HLA-DR alleles carrying the RA-associated shared epitope appeared to have more B cells with autoimmune potential for CCP than those without such HLA alleles (odds ratio 8.1, p = 0.001). In healthy individuals, anti-CCP-producing B cells were also observed more frequently if the RA-associated MHC genes were present (odds ratio 8.0, p = 0.01). Analysis of B cells in cultures may shed light on the interaction of genetic and environmental factors in the development of RA.
22730393 Increased risk of osteoporosis and fracture in women with systemic sclerosis: a comparativ 2012 Dec OBJECTIVE: To investigate whether women with systemic sclerosis (SSc) have an increased risk of osteoporosis (OP) and related fractures compared to a high-risk population with rheumatoid arthritis (RA) and also healthy controls, and to determine putative specific OP and fracture risk factors. METHODS: We performed a cross-sectional study with successive inclusion of age-matched healthy women and women with SSc and RA. Risk factors for OP and fracture were collected for all patients. Bone mineral density (BMD) was systematically measured at the lumbar spine and total hip region with dual x-ray absorptiometry. RESULTS: We included 71 women with SSc, 139 women with RA, and 227 healthy women. The prevalence of OP and fracture was similar in SSc and RA, and was for both diseases higher than in healthy controls (OP: 30% in SSc, 32% in RA, and 11% in controls; fracture: 35% in SSc, 33% in RA, and 10% in controls). Multivariate analysis identified age as a risk factor of OP in SSc. Age and low 25-hydroxyvitamin D (25[OH]D) levels were recognized as risk factors of fracture in SSc. In comparison, age and corticosteroid treatment were associated with OP in RA. Multivariate analysis confirmed age, OP, and low 25(OH)D levels as independent risk factors of fractures in RA. CONCLUSION: The prevalence of OP and fracture in SSc was increased compared to healthy women and reached the high prevalence associated with RA. Age and vitamin D deficiency were identified as risk factors of fracture in SSc. Therefore, increasing the awareness and performance of BMD measurements together with the vitamin D supply in patients with SSc is warranted.
21472758 Estimating transformations for repeated measures modeling of continuous bounded outcome da 2011 Apr 30 Continuous bounded outcome data are unlikely to meet the usual assumptions for mixed-effects models of normally distributed and independent subject-specific and residual random effects. Additionally, overly complicated model structures might be necessary to account adequately for non-drug (time-dependent) and drug treatment effects. A transformation strategy with a likelihood component for censoring is developed to promote the simplicity of model structures and to improve the plausibility of assumptions on the random effects. The approach is motivated by Health Assessment Questionnaire Disability Index (HAQ-DI) data from a study in subjects with rheumatoid arthritis and is evaluated using a simulation study.