tbuckley/cabot-search huggingface dataset:
SAT0458 Urine soluble urokinase plasminogen activator receptor as a potential biomarker of lupus nephritis activity
Authors: S. Burcsár, G. Toldi, B. Szalay, B. Vásárhelyi, L. Kovács, A. Balog
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Over the recent years, soluble urokinase plasminogen activator receptor (suPAR) has been described as a valuable indicator of the activation state of the immune system. Our previous work supported that suPAR might be an objective marker for identifying systemiclupus erythematosus (SLE) patients with active disease. Urokinase plasminogen activator receptor (uPAR) expression is also induced in podocytes during renal diseases such as focal segmental glomerulosclerosis (FSGS). In addition, levels of suPAR were found to be elevated in paediatric and adult patients with FSGS. Current noninvasive laboratory and clinical measures of lupus nephritis (LN) activity are not sensitive or specific enough to reliably measure the course of LN. Improved, noninvasive biomarkers are needed to accurately detect LN activity. <h3>Objectives</h3> To evaluate suPAR in urine as a potential biomarker of renal system-specific disease activity in SLE. <h3>Methods</h3> A prospective follow-up study was designed. 14 SLE patients with newly diagnosed LN and 31 healthy individuals were enrolled in this study. LN was the leading symptom of all SLE patients. Further organ involvements including arthritis, leucopenia, serositis, fever and rash also occurred at the time of LN diagnosis. 12 out of 14 LN were confirmed by renal biopsy. Urine samples were taken before the initiation of LN induction therapy, and monthly thereafter (6 to 11 times).Global and renal disease activity were defined using the <sup>SLE Disease Activity Index 2000</sup> (SLEDAI-2K) and the SLEDAI-2K renal domain score. suPAR concentrations in the urine were measured with the suPARnostic Flex ELISA assay. Nonparametric testing was used for statistical analysis, including the Kruskal-Wallis test and the Mann-Whitney U test. <h3>Results</h3> All urine suPAR levels were elevated in SLE patients with active LN compared with patients with resolved LN and healthy controls (21.75 vs 4.93 and 5.09 ng/mL, respectively, p&lt;0.0001). suPAR levels were higher measured before than after the initiation of LN induction therapy in patients before resolution of active LN (29.46 vs 21.07 ng/mL, p=0.0122). Prospective follow-up measurements also suggested that urine suPAR levels raised again in patients with a relapse of LN according to SLEDAI-2K renal domain score (n=3; 5.45 vs 15.19 ng/mL, p=0.0127). <h3>Conclusions</h3> Urine suPAR is a promising LN activity biomarker, given its isolated elevation in urine in active LN and pronounced decrease with LN improvement. It may potentially become a more convenient alternative to renal biopsy, the current gold standard of LN activity monitoring. <h3>Acknowledgements</h3> Attila Balog was supported by the János Bolyai Scholarship. This work was supported by the GINOP-2.3.2–15–2016–00 030 research found. <h3>Disclosure of Interest</h3> None declared
Bendamustine Adversely Affects Stem Cell Mobilization Among Patients with Mantle Cell Lymphoma (MCL): A Comparison of the BR Vs RCHOP Eras in British Columbia (BC), Canada
Authors: Hatem Alahwal, Parv Chapani, Diego Villa, Yasser Abou Mourad, Maryse Power, Stephen H. Nantel, David Sanford, Gayatri Sreenivasan, Heather J. Sutherland, Laurie H Sehn, Cynthia L. Toze, Raewyn Broady, Kevin Song, Paul Yenson, Alina S. Gerrie
Journal: Blood (2018)
Inhibition of Autophagy with 3-Methyladenine Potentiates Bortezomib-Induced Apoptosis of Myeloma Cell Via up Regulation of Mitochondrial Reactive Oxygen Species
Authors: Yeung-Chul Mun, Jee Young Ahn, Eun Sun Yoo, Kyoung Eun Lee, Eunmi Nam, Soon Nam Lee, Hyun Ae Woo, Sue Goo Rhee, Chu Myong Seong
Journal: Blood (2018)
FRI0041 Associations between tyms polymorphisms and responsiveness to or toxicity of methotrexate in rheumatoid arthritis
Authors: Y.H. Lee, Y.H. Seo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Thymidylate synthase<i> (TYMS)</i> is a key protein in the <i>de novo</i> synthesis of pyrimidines, and is essential for DNA replication and cell proliferation. MTX is polyglutamylated to form MTX polyglutamates after entering cells, and directly inhibits TYMS. TYMS is an important target for MTX, and over-expression of the <i>TYMS</i> gene is associated with resistance to TYMS-targeted drugs. <h3>Objectives</h3> The aim of this study was to investigate whether the thymidylate synthase<i> (TYMS)</i> 2R/3R and 6 bp I/D polymorphisms can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). <h3>Methods</h3> We conducted a meta-analysis of studies on the association between the <i>TYMS</i> 2R/3R and 6 bp I/D polymorphisms and non-responsiveness to or toxicity of MTX in RA patients. <h3>Results</h3> A total of 11 studies involving 1613 patients were considered. Meta-analysis showed no association between the <i>TYMS</i> 2R/3R 3R allele and non-responsiveness to MTX therapy (OR=1.087 CI=0.682–1.731, p=0.726). The meta-analysis indicated that there was no association between the <i>TYMS</i> 6 bp I/D D allele and non-responsiveness to MTX therapy (OR=0.688, 95% CI=0.281–1.683, p=0.413). Meta-analysis revealed no association between the overall toxicity of MTX treatment in RA and the <i>TYMS</i> 2R/3R 3R allele. However, meta-analysis revealed that MTX toxicity was associated with the <i>TYMS</i> 2R/3R polymorphism in RA patients when a co-dominant model (3 R2R vs. 3 R3R+2R2R) was used, indicating that heterozygotes (3 R2R) for the polymorphism had a higher risk of developing MTX toxicity than homozygotes (3 R3R+2R2R). Stratification by ethnicity indicated an association between the <i>TYMS</i> 2R/3R 3R allele and non-responsiveness to MTX in Caucasians, but not in non-Caucasians. In contrast, meta-analysis revealed no association between the overall toxicity of MTX and the <i>TYMS</i> 6 bp I/D D allele. <h3>Conclusions</h3> This meta-analysis demonstrates that the <i>TYMS</i> 2R/3R and 6 bp I/D polymorphisms may not be associated with non-responsiveness to MTX therapy, but that the <i>TYMS</i> 2R/3R polymorphism may be associated with MTX toxicity in RA, particularly in Caucasians. <h3>References</h3> [1] Bohanec Grabar P, Logar D, Lestan B, et al. Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism. European Journal of Clinical Pharmacology2008;64(11):1057–1068. [2] Kremer JM. Toward a better understanding of methotrexate. Arthritis Rheum2004;50(5):1370–1382. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
SAT0301 Similar efficacy of rhu-tnfr-fc tepering and maintenance for hip arthritis in patients with ankylosing spondylitis
Authors: Z. Huang, X. Huang, W. Deng, X. Guo, Y. Huang, T. Li
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hip involvement is common in patients with ankylosing spondylitis (AS) and eventually leads to functional impairment. Recent studies indicated tumour necrosis factor inhibitors (TNFi) might be an effective therapy for hip arthritis in AS patients. However, the conventional dose of TNFi associates with high cost and increasing risk for adverse effects, so dose reduction is necessary. <h3>Objectives</h3> We compared the efficacy between recombinant human soluble tumour necrosis factor receptor II: IgG Fc fusion protein (Rhu-TNFR-Fc) dose reduction and maintenance in terms of disease activity, function and change of imaging examination. <h3>Methods</h3> Fifty-one AS patients (102 hips) who admitted to our hospital from January 2015 to December 2017 were involved in this retrospective cohort study. Patients who had previously received disease modifying anti-rheumatic drugs or systemic glucocorticoid therapy were excluded. After being treated by Rhu-TNFR-Fc (YISAIPU) 50 mg/week for 12 weeks, subcutaneous injections were performed every other week for patients in the tapering group, while the control group maintained the same therapy till the 24th week. AS disease activity score-C reactive protein (ASDAS-CRP), Bath AS function index (BASFI) and Harris hip score were recorded at every follow-up. Pelvic X-ray and MRI examinations for hips were conducted before treatment and in the 24th week. Bath AS radiology index-hip (BASRI-h) was employed to assess the change in X-ray, and definition of hip MRI finding was described by Huang et al. Bone marrow oedema, enthesitis and synovitis was thought to be a marker for active inflammatory changes. Chronic inflammatory changes included bone erosion, fat accumulation and ankylosis. <h3>Results</h3> After markedly descending to the minimum at week 12 (p&lt;0.05), ASDAS-CRP, BASFI and Harris hip score kept stable till the end in both groups (table 1). BASRI-h of these groups unchanged during 24 weeks (p&gt;0.05, figure 1). Nevertheless, active inflammatory changes improved dramatically in the second MRI examination (p&lt;0.05, table 2). No statistical significant was existed between groups (p&gt;0.05). <h3>Conclusions</h3> Rhu-TNFR-Fc tapering might maintain remission of hip arthritis in patients with AS, and it shares similar therapeutic effect of full-dose Rhu-TNFR-Fc. Therefore, dose reduction of TNFi tends to be an acceptable therapy for AS-related hip arthritis. <h3>Reference</h3> [1] Eur J Radiol. 2013;82(9):1487–93. <h3>Disclosure of Interest</h3> None declared
Pilot Prospective Phase II Study of Nilotinib Combined with Chemotherapy for Myeloid Blastic Phase of Chronic Myeloid Leukemia or Acute Myeloid Leukemia with BCR/ABL1
Authors: Hawk Kim, Yunsuk Choi, Sung-Soo Yoon, Won-Sik Lee, Jee Hyun Kong, Kyoo-Hyung Lee, Jeong-Yeal Ahn, Sang Kyun Sohn
Journal: Blood (2018)
AB1211 Utility of pet/ct for the diagnosis and disease manegement: a study of 88 patients from an autoimmune diseases hospital unit in a 2-year period
Authors: P. Diéguez, A. Argibay, C. Vázquez Triñanes, B. Gimena, M. Estévez, R. Lorenzo, N. Val, M. Freire, A. Rivera
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) is a non-invasive imaging technique commonly used in clinical oncology. 18 F-FDG accumulation is recognised as useful for diagnosing and monitoring the response to therapy in patients with some inflammatory disorders, but the role of the PET/TC in the management of these diseases is debated. <h3>Objectives</h3> The aim of this study was to investigate the role of 18F-FDG PET/CT in the diagnosis of the disease and assessing disease activity in an autoimmune diseases unit, and to evaluate if the results of this image technique imply a change in clinical management. <h3>Methods</h3> We retrospectively reviewed all 18F-FDG PET/CT requested since August 2015 to August 2017 by our unit. Data collected were: patient demographics, reason for PET request, PET results and change in therapy. <h3>Results</h3> PET/CT were performed in 88 patients and were positive in 68 (77,3%) cases. Patients (49 women/39 men) had a mean age of 58,1±15,7 years (range, 27–92 years). The clinical diagnosis at the moment of ordering the PET/CT were: sarcoidosis (n=45), large-vessel vasculitis (LVV) (n=16), immunoglobulin G4-related disease (IgG4-RD) (n=9), collagen-vacular diseases (CVD) (n=7), mesenteric panniculitis (n=4), myopathy (n=4), polymyalgia rheumatica (PMR) (n=2) and ANCA-associated vasculitis (n=1). (See <b>table 1</b>). PET results supported a change in therapeutic management in 71.6% of the cases. In the group of sarcoidosis there was a change in treatment in 68.9% of cases. PET/TC revealed extrapulmonary manifestations in 57,8%. All patients with extracranial manifestations of giant cell arteritis (GCA) showed uptake in PET/TC. That result supported the clinical diagnosis, although negative temporal artery biopsy. PET was useful in the diagnosis and treatment of IgG4-RD in 66,7% of cases. PET scan did not find malignancy in inflammatory myopathies nor mesenteric panniculitis. <h3>Conclusions</h3> PET/TC is an increasingly utilised in our patients with inflammatory disorders as a support for the diagnosis and management. PET/TC detection extrapulmonary sarcoidosis may have therapeutic and prognostic clinical implications. PET may be useful in patients with GCA supicion with negative biopsy and extracranial symptoms. More studies will be necessary to establish the real role of PET/TC in autoimmune and inflammatory diseases. <h3>Disclosure of Interest</h3> None declared
AB0389 Hipertriglyceridemic-waist phenotype: a marker of cardiovascular risk in rheumatoid arthritis patients
Authors: I.P. Guzmán Guzmán, O. Zaragoza-García, J.E. Navarro-Zarza, J. Maldonado-Anicacio, N. Castro-Alarcón, I. Parra-Rojas
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The risk of cardiovascular disease (CVD) is increased in rheumatoid arthritis (RA); about 50% of associated deaths in rheumatoid arthritis (RA) are attributed to CVD.<sup>1</sup> Both traditional cardiovascular risk (CVR) factors and inflammation contribute to this risk. The hyperuricemia (HUC) and metabolic syndrome (MetS) are considered parameters of CVR, both closely related,<sup>2</sup> and recently the hypertriglyceridemic-waist (HTGW) phenotype has been defined as well a marker to identify HUC in the general population.<sup>3</sup> <h3>Objectives</h3> To determine the prevalence of HTGW phenotype and to evaluate its association with CVR parameters among RA patients. <h3>Methods</h3> HTGW phenotype was defined as waist girth ≥102 cm in male and ≥88 cm in female and TG &gt;150 mg/dl in 250 patients diagnosed with RA according to the ACR/EULAR 2010 criteria. The levels of uric acid &gt;5.5 mg/dL defined HUC. The MetS and its individual components (NCEP-ATPIII) were evaluated as parameters of CV risk. <h3>Results</h3> We identified 51 AR patients (20.4%) whith HTGW phenotype. Adjusting for covariates in a logistic regression model, it was observed that the HTGW phenotype is associated with the presence of HUC (OR=6.14, p≤0.001), and MetS (OR=5.7, IC95%, 2.7–12.2, p≤0.001). <h3>Conclusions</h3> HTGW is prevalent in RA patients from southern Mexico. The HTGW phenotype can be considered at low cost marker, used as a tool screening to predict high metabolic risk during the clinical course of the rheumatic disease. <h3>References</h3> [1] Goshayeshi L, Saber HR, Sahebari M, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol2012;31:1–7. [2] Abbasian M, Ebrahimi H, Delvarianzadeh M, et al. Association between serum uric acid (SUA) levels and metabolic syndrome (MetS) components in personnel of Shahroud university of medical sciences. Diabetes Metab Syndr2016;10:132–6. [3] Chen S, Guo X, Dong S, et al. Association between the hypertiglyceridemic waist phenotype and hyperuricemia: a cross-sectional study. Clin Rheumatol2017;36(5):1111–1119. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> None declared
Atheroma Niche‐Responsive Nanocarriers for Immunotherapeutic Delivery
Authors: Erica B. Peters, Nick D. Tsihlis, Mark R. Karver, Stacey M. Chin, Bruno Musetti, Benjamin T. Ledford, Edward M. Bahnson, Samuel I. Stupp, Melina R. Kibbe
Journal: Advanced Healthcare Materials (2019)

Nanomedicine is a promising, noninvasive approach to reduce atherosclerotic plaque burden. However, drug delivery is limited without the ability of nanocarriers to sense and respond to the diseased microenvironment. In this study, nanomaterials are developed from peptide amphiphiles (PAs) that respond to the increased levels of matrix metalloproteinases 2 and 9 (MMP2/9) or reactive oxygen species (ROS) found within the atherosclerotic niche. A pro-resolving therapeutic, Ac2-26, derived from annexin-A1 protein, is tethered to PAs using peptide linkages that cleave in response to MMP2/9 or ROS. By adjusting the molar ratios and processing conditions, the Ac2-26 PA can be co-assembled with a PA containing an apolipoprotein A1-mimetic peptide to create a targeted, therapeutic nanofiber (ApoA1-Ac226 PA). The ApoA1-Ac2-26 PAs demonstrate release of Ac2-26 within 24 h after treatment with MMP2 or ROS. The niche-responsive ApoA1-Ac2-26 PAs are cytocompatible and reduce macrophage activation from interferon gamma and lipopolysaccharide treatment, evidenced by decreased nitric oxide production. Interestingly, the linkage chemistry of ApoA1-Ac2-26 PAs significantly affects macrophage uptake and retention. Taken together, these findings demonstrate the potential of PAs to serve as an atheroma niche-responsive nanocarrier system to modulate the inflammatory microenvironment, with implications for atherosclerosis treatment.
P071/O13 RNA sequencing detection of gene dysregulation in B cells sorted from salivary gland tissue and from peripheral blood reveals new pathways involved in primary sjÖgren’s syndrome pathophysiology
Authors: E Rivière, N Tchitchek, G Nocturne, J Pascaud, S Boudaoud, A Thai, N Allaire, B Jagla, M Mingueneau, X Mariette
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD. <h3>Introduction</h3> Primary Sjögren's syndrome (pSS) is a chronic auto-immune disorder characterized by lymphocytic infiltrates and destruction of the salivary glands (SG). Chronic B cell activation, the secretion of autoantibodies and the critical role of BAFF have been demonstrated. However, mechanisms leading to B cells dysregulation remain partially understood. <h3>Objectives</h3> To establish transcriptomic maps of the B cells sorted from the SG and from blood in pSS patients and controls using RNASeq. <h3>Methods</h3> Patients had pSS according to 2016 EULAR/ACR criteria and controls had sicca symptoms without any antibodies and with normal SG biopsy. B cells were sorted from SG biopsies and from blood using a FACS ARIA. RNASeq profiling was performed using MiSeq. Statistical analysis identified differentially expressed genes between pSS and controls in B cells sorted from SG (9 pSS, 4 controls), from blood (16 pSS, 7 controls); and between B cells sorted from SG and blood in the same patients (4 pSS patients). Functional enrichment analysis used Ingenuity Pathway Analysis. <h3>Results</h3> The pSS vs controls comparison in B cells sorted from SG identified up-regulated genes involved in activation of B cells including CD48, CD22 and CD40. TLR10, which is involved in innate immunity was also up-regulated in pSS. In blood B cells, TLR7 and the downstream signaling molecule IRF7 were up-regulated in pSS. Additionally, IL-6 which is involved in B cells growth was up-regulated. Enrichment analysis highlighted EIF2 signaling pathway, interferon (IFN) signaling pathway and role of JAK in IFN signaling. The paired comparison between B cells from SG and from blood identified up-regulated genes including CD138, a plasma cell marker, IL-6, TLR5 and IFN induced genes. The confirmation by qPCR of these results is ongoing. <h3>Conclusions</h3> This study allowed to explore the mechanisms that support B cell activation in pSS focusing on tissue resident and circulating cells. Data confirmed B cell activation and differentiation through several markers and highlighted the role of innate immunity and key pathways including IFN and JAK signaling. Precise understanding of these dysregulations should offer development of new targeted therapeutic perspectives. <h3>Disclosure of Interest</h3> None declared.
FRI0451 Continuous presence of igm anti-topoisomerase i antibodies indicates an ongoing immune response in systemic sclerosis
Authors: M. Boonstra, J.A. Bakker, A. Grummels, M.K. Ninaber, N. Ajmone Marsan, H.U. Scherer, R.E. Toes, T.W. Huizinga, J.K. de Vries-Bouwstra
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Small case-series of anti-topoisomerase I antibodies (ATA) in Systemic Sclerosis (SSc) show a highly varying immune response over time. IgA and IgG levels were shown to correlate with skin scores. One small study showed that increasing IgG levels can precede increasing skin scores. Thus far, detailed analysis of ATA characteristics with disease features in larger cohorts have not been performed. <h3>Objectives</h3> By taking advantage of our well described SSc cohort with annual follow-up data, we aimed to evaluate whether clinical heterogeneity within ATA +patients can be explained by ATA characteristics. <h3>Methods</h3> ATA IgG, IgM and IgA levels were assessed in consecutive serum samples of baseline ATA-IgG +patients from the Leiden SSc cohort. Disease progression during the first year of follow-up was defined as increase of modified Rodnan Skin Score (mRSS) with ≥5 points, progression of pulmonary involvement (-≤10% of predicted forced vital capacity [FVC] or diffusion capacity of the lung [DLCO]), development of digital ulcers, renal crisis, pulmonary arterial hypertension and/or mortality. Here, we present data on the association between the presence of ATA-IgM and disease progression. <h3>Results</h3> In total 344 samples of 102 ATA +patients were measured. Baseline and follow-up samples were available from 70 patients. Median follow-up was 3.7 years (range 0.9–7.4 years). At baseline 42/70 patients were positive for ATA IgM and 69/70 patients for ATA IgA (table 1). Strikingly, while clinical characteristics did not differ, mean ATA-IgM at baseline was higher in disease progressors (table 2). The possible relevance of an ATA-IgM response for disease progression was confirmed by the observation that of those patients positive for ATA-IgM both at baseline and at FU, 59% of cases showed disease progression, as compared to 15% of patients negative for ATA IgM at both time points (p=0.02). <h3>Conclusions</h3> The presence of ATA-IgM at baseline and at follow-up and its association with disease course suggests that the ATA response in SSc patients is an ongoing process that possibly explains the heterogenic disease course of ATA +patients over time. <h3>Disclosure of Interest</h3> None declared