tbuckley/cabot-search huggingface dataset:
SAT0031 Detection and isolation of antigen specific b cells in patients with rheumatoid arthritis
Authors: J Nilsson, M Bergquist, K Önnheim, I-L Mårtensson, J Viljanen, E Lönnblom, B Xu, O Sareila, J Kihlberg, R Holmdahl, I Gjertsson
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The majority of autoimmune diseases, e.g. rheumatoid arthritis (RA), are characterized by autoantibodies that are produced by B cells. We have identified several novel post-translationally modified epitopes in collagen type II (CII), a major cartilage constituent that are autoreactive. In mouse models, autoantibodies that bind to these epitopes can either induce or protect against inflammatory arthritis. However, very little is known about the frequencies or phenotype the B cells that produce these autoantibodies in humans. <h3>Objectives</h3> The aim of this project is to study the B cells that produce autoantibodies reactive to CII-epitopes in patients with RA. <h3>Methods</h3> Clinical data and peripheral blood were collected from patients with RA (n=100). Titres of CII-reactive serum-autoantibodies were determined by Luminex. The different subsets of B cells that expressed a CII-reactive B cell receptor (BCR) were analysed and isolated in patients with positive (n=10) or negative (n=5) titres for autoantibodies recognizing the CII-epitopes cyc48 (CII-F4-R-Cit) and cyc49 (CII-F4-Cit-R) as well as in healthy controls (n=3) using flow cytometry. <h3>Results</h3> In patients with detectable autoantibodies to cyc48 and cyc49, their titres were 13761±3815 and 5585±1992 (mean ± SEM), respectively. The corresponding titres in the patients negative for these autoantibodies were 122±55 and 234±75. In autoantibody-positive patients, the frequencies of cells expressing a BCR reactive for cyc48 and cyc49 in different subsets were: transitional cells 0.88±0.18% and 1.33±0.33%; naïve cells 0.09±0.0008% and 0.13±0.06 and memory cells 0.31±0.25 and 0.30±0.12%. All frequencies were well above those detected in patients without cyc48/49 titres and in healthy controls. A higher proportion (p=0.03) of the cyc48/49 positive patients were treated with methotrexate compared to cyc48/49 negative patients, no other clinical differences were recorded. CII-reactive single B cells were isolated in order to clone the BCR <h3>Conclusions</h3> In patients with manifest RA there is a relatively high and detectable frequency of transitional B cells that express a joint-specific BCR, which suggests that the deletion of autoreactive B cells in the bone marrow in RA patients is defective. As there is a decrease in the proportion of naïve CII-specific B cells, a substantial amount of the autoreactive cells are deleted in the periphery. However, peripheral B-cell tolerance is incomplete, as CII-specific B cells are enriched in the pool of memory B cells. <h3>Disclosure of Interest</h3> None declared
Persistence With Dabigatran Therapy at 2 Years in Patients With Atrial Fibrillation
Authors: Miney Paquette, Lionel Riou França, Christine Teutsch, Hans-Christoph Diener, Shihai Lu, Sergio J. Dubner, Chang Sheng Ma, Kenneth J. Rothman, Kristina Zint, Jonathan L. Halperin, Menno V. Huisman, Gregory Y.H. Lip, Robby Nieuwlaat
Journal: Journal of the American College of Cardiology (2017)

Guidelines recommend long-term oral anticoagulation therapy for stroke prevention in patients with atrial fibrillation (AF). Treatment discontinuation rates in vitamin K antagonist (VKA)-treated patients are high but may be lower with non-VKA oral anticoagulant agents.The goal of this study was to describe and explore predictors of dabigatran etexilate persistence in patients with newly diagnosed AF over 2 years of follow-up.Consecutive patients newly diagnosed with AF and ≥1 stroke risk factor were followed up for 2 years. Dabigatran nonpersistence was defined as discontinuation of dabigatran for >30 days. A multivariable Cox regression model included region as well as patient clinical and sociodemographic characteristics to explore predictors of nonpersistence.Eligible patients (N = 2,932) took ≥1 dabigatran dose; their mean age was 70.3 ± 10.2 years, and 55.3% were male. The 2-year probability of dabigatran persistence was 69.2%. Approximately 7% switched to a factor Xa inhibitor and 6% to a VKA. Approximately one-third of dabigatran discontinuations were primarily due to serious or nonserious adverse events. Patients from North America had the highest discontinuation risk, and Latin America had the lowest. Minimally symptomatic or asymptomatic AF and permanent AF were associated with a lower risk for dabigatran nonpersistence. Previous proton pump inhibitor use was associated with a higher risk for dabigatran nonpersistence.Probability of treatment persistence with dabigatran after 2 years was approximately 70%. Nearly one-half of the patients who stopped dabigatran switched to another oral anticoagulant agent. Patients from North America, and those with paroxysmal, persistent, or symptomatic AF, may be at a higher risk for discontinuing dabigatran.
THU0365 Do extra-articular manifestations affect the choice of biologic therapy in patients with axial spondyloarthritis? a multicentre real-life analysis
Authors: EG Favalli, S D'Angelo, A Carletto, A Becciolini, F Martinis, G Tramontano, MG Raimondo, M Biggioggero, A Marchesoni, M Rossini, I Olivieri
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Extra-articular manifestations (EAMs), such as uveitis, inflammatory bowel diseases (IBD) and psoriasis (PsO), frequently complicate the disease course of patients with axial spondyloarthritis (axSpA), although prevalence data on this regard are still controversial. The occurrence of EAMs might also contribute to the decision of introducing a biologic therapy and even influence the choice between the available TNF inhibitors (TNFis). <h3>Objectives</h3> The aim of this study is to retrospectively evaluate the prevalence of EAMs in a multicentre cohort of axSpA patients treated with TNFi, investigating how these influenced the choice of treatment. <h3>Methods</h3> Clinical data from axSpA patients treated with a TNFi between May 2003 and May 2016 where obtained from a multicentre registry. Prevalence of EAMs (uveitis, IBD and PsO) was calculated at the time of TNFi prescription, evaluating their distribution according to drug subgroup. <h3>Results</h3> The study included 503 patients with axSpA (172 [34.2%] women, mean age [±SD] 40.5 [±13.2] years, mean disease duration 9.7 [±14.7] years), receiving a total of 675 lines of treatment (I-line n=503, II-line n=118, ≥ III-line n=54) with a TNFi (272 infliximab [IFX], 173 adalimumab [ADA], 89 golimumab [GOL], 141 etanercept [ETN]). At the time of TNFi introduction, 28.6% patients claimed at least one EAM (IBD 11.3%, uveitis 10.9%, and PsO 8.8%). The baseline presence of at least one EAM was associated with a more frequent prescription of an anti-TNF monoclonal antibody rather than etanercept (34.1% versus 21.9%, respectively; p=0.005). In detail, EAMs were found in 41.6, 36.9, 29.8, and 21.9% patients treated with GOL, ADA, IFX, or ETN, respectively. The prevalence of IBD was significantly higher (p=0.004) in patients treated with ADA (12.7%), IFX (14.3%), or GOL (11.2%) compared with ETN (4.9%). Uveitis was numerically more frequent in GOL (20.2%) and ADA (13.3%) rather than IFX (9.5%) and ETN (9.9%) groups. Finally, PsO prevalence was similar in patients treated with ADA (10.9%) and GOL (10.1%), and numerically lower in the ETN (7.1%) and IFX (5.9%) groups. <h3>Conclusions</h3> In our cohort of axSpA patients treated with TNFis, EAMs were highly represented. The presence of extra-articular involvement has been carefully taken into account when a TNFi was required to better control the disease. In particular, IBD and uveitis drove more frequently the choice toward an anti-TNF monoclonal antibody instead of the receptor. <h3>Disclosure of Interest</h3> None declared
THU0289 B-cell activating factor gene expression in urinary sample and renal biopsy for monitoring disease activity in lupus nephritis
Authors: S Retamozo, L Mas, MJ Haye Salinas, V Saurit, F Caeiro, A Diller, J De La Fuente, M Angelina, NR Benzaquen, JP Pirola, A Alvarellos, T Alvarellos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To evaluate BLyS as biomarker in disease activity in urinary sample and renal biopsy from patients with LN. <h3>Methods</h3> Retrospective study. Between June 2009 and October 2013, 32 patients with SLE and LN fullfilling SLE classification criteria of ACR 1997 were included. The renal biopsies were evaluated according to the ISN/RPS classification system. The gene expression levels of BLyS were quantified using Quantitative Real Time PCR (QPCR). The relative quantification method was used for analysis, where Ct was normalized to an endogenous control β2Microglobulina (β2M) (ΔCt BLyS). The data expressed as ΔCt are inversely proportional to gene expression level. The value of BLyS is expressed as median (M) and interquartile range (IQR) for filing a non-normal distribution. <h3>Results</h3> 26 (81.3%) patients were female with a mean age at diagnosis of 26.9±13 years and 31.9±29 years at the time of renal biopsy. The SLEDAI at the time of biopsy was 10.5 (IQR 0–15.7) and SLICC ≥1 in 13 (32.5%), hypocomplementemia 13/31 (41.9%) and positive DNA in 11/29 (37.9%) patients. Biopsies from patients with proteinuria ≥0.5 and renal failure (RF) (n=23, 71.9%), proteinuria isolated (n=14, 43.8%), LN remission. The value of the BLyS gene expression in renal biopsy was 8.09 (IQR 7.37–9.16) and BLyS in urinary sample was 6.45 (IQR 5.62–7.76). <h3>Conclusions</h3> BLyS detection in urinary samples could be a potential biomarker for predicting lupus nephritis activity. Our data confirm that the BLyS as urinary biomarker is present in patients with active renal disease especially in patients with proliferative glomerulonephritis. <h3>Disclosure of Interest</h3> None declared
SP0130 Win session: osteoporosis
Authors: P Geusens
Journal: Annals of the Rheumatic Diseases (2017)

The clinical pathway for fracture prevention consists of a 5-step approach: case finding, risk evaluation, differential diagnosis, treatment and follow up. For each of these steps new insights have emerged during the last year. Epidemiologic studies have shown that not only fracture risk, but also mortality is increased after fracture, and that adequate therapy can not only decrease fracture risk but also increase survival. Fracture risk is not constant over time. It is highest the years following a fracture, and immediately increases in some instances, such as after starting glucocorticoids or androgen deprivation therapy. This has raised the concept of "imminent" fracture risk, in contrast to long-term fracture risk as included in FRAX. In this context, we present the the EULAR initiative, in collaboration with EFORT, that published recommendations for multidisciplinary acute fracture care, including orthogeriatric care after hip fracture, and subsequent fracture prevention at the Fracture Liaison Service. The presence, number and severity of vertebral fractures contribute to fracture risk, independent of BMD. Most vertebral fractures are subclinical and can therefore only be diagnosed by imaging of the spine. The role of vertebral fracture assessment (VFA) using DXA will be discussed. New treatment insights will be reviewed, including for glucocorticoid users, combined and sequential treatments with anti-resorptive and bone forming drugs, real world data and the role of fall prevention. Prescription of and adherence to treatment are still major issues. In patients adherent to therapy, new insights and recommendations will be reviewed on the need for early treatment, duration of treatment and the clinical approach when considering stopping drug therapy. <h3>Disclosure of Interest</h3> P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Roche, UCB, BMS, Novartis, Consultant for: Amgen
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases
Authors: Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O’Loughlin, Yang Xu, Zain Fanek, David J. Greco, Scott T. Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D. Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L. Heppner, Vladimir Litvak, David M. Holtzman, Hans Lassmann, Howard L. Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Journal: Immunity (2017)
Aptamer-Based Therapeutic Approaches to Target Cancer Stem Cells
Authors: Gang Zhou, Olivier Latchoumanin, Mary Bagdesar, Lionel Hebbard, Wei Duan, Christopher Liddle, Jacob George, Liang Qiao
Journal: Theranostics (2017)

Cancer stem cells (CSCs) are believed to be a principal cellular source for tumour progression and therapeutic drug resistance as they are capable of self-renewal and can differentiate into cancer cells.Importantly, CSCs acquire the ability to evade the killing effects of cytotoxic agents through changes at the genetic, epigenetic and micro-environment levels.Therefore, therapeutic strategies targeting CSCs hold great potential as an avenue for cancer treatment.Aptamers or "chemical antibodies" are a group of single-stranded nucleic acid (DNA or RNA) oligonucleotides with distinctive properties such as smaller size, lower toxicity and less immunogenicity compared to conventional antibodies.They have been frequently used to deliver therapeutic payloads to cancer cells and have achieved encouraging anti-tumour effects.This review discusses progress in CSC evolution theory and the role of aptamers to target CSCs for cancer treatment.Challenges of aptamer-mediated CSC targeting approaches are also discussed.
AB0565 Insufficient influenza vaccination coverage in giant cell arteritis. a french population-based study
Authors: G Pugnet, M Lapeyre-Mestre, M Mounie, G Moulis, L Sailler
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> French general health insurance scheme has implemented a national influenza vaccination program, including full refund for those 65 years old or more. Despite this program, only 62.6 to 71% of people aged over 65 years are vaccinated and no data are available regarding influenza vaccination coverage (IVC) in GCA. <h3>Objectives</h3> To evaluate the rate and the factors associated with seasonal influenza vaccination coverage in incident giant cell arteritis (GCA) patients compared with controls. <h3>Methods</h3> Using the French National Health Insurance system (SNIIRAM), we included patients with incident GCA from the Midi-Pyrenees region, southern France, and randomly selected 6 controls matched by sex and age at calendar date from January 2005 to December 2008 and followed them till April 2011. The vaccination rate was estimated from vaccine dispensation registered in the SNIIRAM. IVC was compared between GCA and their controls using longitudinal multivariate Poisson regression. <h3>Results</h3> Eighty-seven incident GCA patients over 65 years of age and 509 in the control group were included. Mean follow-up was 4.4±1.2 and 4.2±1.2 years, respectively. During the yearly influenza campaigns from 2005–2006 to 2010–2011, the IVC rates in the GCA group and the control group ranged from 60.8 to 74.7% vs 56.6 to 70.4%, respectively. Incident GCA influenza vaccination rate was 20% higher than controls (RR=1.20; IC 1.09 to 1.32, P&lt;0.001) (Table 1). <h3>Conclusions</h3> Rates of recommended influenza vaccinations are insufficient in GCA patients over 65 years. More attention should be paid for appropriate vaccination during GCA course. <h3>Disclosure of Interest</h3> None declared
AB0072 Rational designed gold nanoparticle suppresses rankl-induced osteoclastogenesis in raw264.7 cells via NF-KAPPA B pathway and MAPK pathways
Authors: Q Yuan, X Gao
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Bone erosion in joint is the most deleterious effect induced by rheumatoid arthritis (RA) and is the major cause of disability. New therapies are urgently required to prevent RA-associated bone destruction. The excessive bone resorption in RA was proved to be mediated by osteoclasts which are derived from the monocyte/macrophage lineage and induced by RANKL. Therefore, RANKL could be a potential target for the preservation of bone mass in RA. <h3>Objectives</h3> Chrysotherapy showed potential effects in reducing of joint destruction but with serious side-effects in RA therapy. A rational designed gold nanoparticle named GN was prepared to provide a choice for suppressing bone loss in RA therapy with more safety. <h3>Methods</h3> Mice macrophage cell line RAW264.7 was activated by RANKL to evaluate the potential osteoclastogenesis suppressing effects of GN. The differentiation, fusion and function of osteoclast were assessed by tartrate-resistant acid (TRAP) staining, actin ring formation assay and osteologic discs detection respectively. Relative expressions of osteoclast-specific genes were evaluated by RT-PCR and the activity of NF-κB pathway as well as MAPK pathways were analyzed by immunoblotting. <h3>Results</h3> Osteoclast differentiation, fusion and bone resorption were activated by RANKL in RAW264.7 cell, while GN significantly attenuates this process in a dose-dependent manner. The expressions of osteoclast-specific genes including TRAP and OSCAR were increased by RANKL stimulation but were effectively suppressed by GN. The activation of NF-kappa B pathway and MAPK pathways induced by RANKL was also suppressed by GN treatment. <h3>Conclusions</h3> Our findings revealed that treatment with GN could prevent RANKL-induced osteoclastogenesis and reduce increased expression of osteoclast-specific genes which may through the suppression of NF-kB and MAPK activation in macrophage. GN may provide a basis for the design of chrysotherapy drugs that effect in progression of RA-associated articular erosions. <h3>Disclosure of Interest</h3> None declared
THU0687 Feasibility and validity of promis® global health short form (PROMIS10) in outpatients with SLE
Authors: S Kasturi, J Szymonifka, J Burket, J Berman, K Kirou, A Levine, L Sammaritano, LA Mandl
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Routine measurement of patient reported outcomes (PROs) is a priority for improving quality of care and outcomes in chronic rheumatic conditions including systemic lupus erythematosus (SLE). Measuring PROs at the point of care requires validated instruments with minimal responder burden. PROMIS10 is a 10 question universal (non-disease specific) PRO instrument measuring physical and mental health domains with T-scores normalized to the general population (mean score =50). The feasibility and validity of PROMIS10 have not been demonstrated in SLE. <h3>Objectives</h3> To evaluate: 1) feasibility and 2) validity of PROMIS10 in outpatients with SLE. <h3>Methods</h3> Adults meeting 1997 ACR SLE classification criteria were recruited from an SLE Center of Excellence. Subjects completed SF-36, LupusQoL-US, selected PROMIS Computerized Adaptive Tests (CATs), and PROMIS10. Construct validity was evaluated using Spearman9s correlations comparing PROMIS10 physical and mental health scores with PROMIS CATs and legacy instruments. Test-retest reliability was evaluated in subjects reporting stable SLE activity at 2 assessments a week apart with intraclass correlation coefficients (ICCs). Focus groups of participants evaluated the relevance and utility of PROMIS10. <h3>Results</h3> 204 (86%) of 238 patients approached, enrolled. There were no statistically significant differences in demographic characteristics between participants and non-participants. SLE patients scored worse than the general population in PROMIS10 physical health (mean T-score 41.6 +/- SD 8.8; range 19.9 - 67.7) and mental health (mean T-score 43.7 +/- SD 8.7; range 25.1 - 67.6). PROMIS10 physical health scores correlated strongly with physical function, pain, and social health domains in PROMIS CATs, SF-36, and LupusQoL, while PROMIS10 mental health scores correlated strongly with PROMIS depression CAT and SF-36 and LupusQoL mental health domains (Table 1). Test-retest reliability for both PROMIS10 physical and mental health scores was high with ICCs of 0.89 and 0.85 respectively. Median time to complete PROMIS10 was &lt;2 minutes. Focus group participants found PROMIS10 relevant and useful. <h3>Conclusions</h3> PROMIS10 is feasible to administer to outpatients with SLE and valid compared to legacy instruments. PROMIS10 can be used to quickly, accurately, and reliably screen for impaired physical function, pain, and depression and could be an important tool in the measurement of patient centered outcomes and improvement of quality of care in SLE. <h3>Disclosure of Interest</h3> None declared
AB1132 Higher rates of obesity and associations with poorer clinical status in patients with RA, OA and SLE: a cross-sectional study from routine care
Authors: I Castrejon, N Shakoor, JA Block, T Pincus
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Obesity is a risk factor for many chronic rheumatic diseases. In rheumatoid arthritis (RA), obesity is associated with increased comorbidities, higher medical costs, disease activity, and poorer physical function<sup>1</sup>. In OA, obesity is a risk factor for both incidence and progression, and has a negative impact on outcomes<sup>2</sup>. In systemic lupus erythematous (SLE), obesity is associated with more severe renal involvement, lower quality of life, and increased cardiovascular risk<sup>3</sup>. <h3>Objectives</h3> To assess associations of obesity with patient self-report multidimensional health assessment questionnaire (MDHAQ) scores and physician global assessments in patients with RA, OA and SLE seen in routine care. <h3>Methods</h3> All patients at one academic center complete a MDHAQ, which includes a 0–10 scale for physical function (FN), 0–10 visual analogue scales (VAS) for pain (PN) and patient global assessment (PATGL), compiled into a 0–30 RAPID3, as well as scales for fatigue, depression, and demographic data. Physicians complete a VAS for patient global (DOCGL). Body Mass Index (BMI) was calculated from the medical record as weight (kg)/ height (meters)<sup>2</sup>. Patients were classified by BMI as normal (18.5–25), overweight (25–30), or obese (&gt;30) according to the WHO guidelines. Demographic and clinical MDHAQ data were compared in the 3 diagnostic groups according to BMI groups using ANOVA and chi-square tests. <h3>Results</h3> 396 patients with RA, 425 with OA, and 306 with SLE were studied. Obesity was reported by 40% of RA and SLE patients, and 59% of OA patients, a higher percentage than matched individuals in the general population in the same region (30.8%). Obesity was higher in African-American patients (48% in RA, 70% in OA, and 53% in SLE). Education level, gender, and age did not differ significantly across the groups. Obesity was associated with poorer physical function, poorer patient global and higher pain in all 3 diagnostic groups, with higher depression scores in OA and SLE (Table). DOCGL was significantly higher only in OA (data not shown). <h3>Conclusions</h3> Obesity is more prevalent in patients with rheumatic diseases compared with the general population. Obese patients had poorer status on most MDHAQ scores, particularly physical function and pain. Obesity is an important comorbidity in patients with rheumatic diseases. <h3>References</h3> J Rheumatol 2015, 42(12):2261–2269. Obes Rev 2014, 15(7):578–586. Autoimmunity Reviews 2014;13: 981–1000. <h3>Disclosure of Interest</h3> I. Castrejon: None declared, N. Shakoor: None declared, J. Block: None declared, T. Pincus Shareholder of: Health Report Services, Inc