tbuckley/cabot-search huggingface dataset:
THU0007 IL-26 PROMOTES OSTEOCLASTOGENESIS IN RHEUMATOID ARTHRITIS
Authors: Sang-Heon Lee, Kyung Ann Lee, Hae-Rim Kim
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> IL-26 is a 171-amino acid protein, which is classified as a member of the Th17 cytokine family. The role of IL-26 in osteoclastogenesis in RA is needed to be clarified to understand the pathogenesis of RA. <h3>Objectives:</h3> To examine the functional role of interleukin-26 (IL-26) in the expression of RANKL and induction of osteoclastogenesis in rheumatoid arthritis (RA). <h3>Methods:</h3> The expression of IL-20Rα, CD55 and RANKL in RA synovial fibroblasts was analyzed using confocal microscopy. RA Fibroblasts like synoviocytes (RA-FLS) were treated with recombinant human IL-26, and the expression of RANKL messenger RNA (mRNA) and protein was measured using real-time polymerase chain reaction and ELISA. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrateresistant acid phosphataseepositive multinucleated cells. Osteoclastogenesis was also evaluated after monocytes were co-cultured with IL-26-prestimulated FLS. <h3>Results:</h3> The IL-26 concentration in the FLS was higher in RA patients than in patients with osteoarthritis (OA). In RA-FLS treated with rhIL-26, the expression of RANKL mRNA and protein was increased in a dose-dependent manner. IL-26 increased the expression of RANKL in RA-FLS, and the IL-26-induced RANKL expression decreased by the inhibition of IL-20Rα. IL-26–induced RANKL expression was down-regulated significantly by the inhibition of SHP-1, ERK, JNK, stat1, c-jun or p38 MAPK/NF-κB signaling. When monocytes isolated from human peripheral blood were cultured with IL-26, they were differentiated into osteoclasts in the absence of RANKL. Monocytes were also differentiated into osteoclasts when they were cocultured with IL-26–pretreated RA-FLS <h3>Conclusion:</h3> IL-26 has a dual effect on osteoclastogenesis in RA: 1) direct induction of osteoclastogenesis from monocytes and 2) up-regulation of RANKL production in RA-FLS. This IL-26/RANKL axis could be a potential therapeutic target for bone destruction in RA. <h3>Reference:</h3> [1] Corvaisier M, Delneste Y, Jeanvoine H, et al. IL-26 Is Overexpressed in Rheumatoid Arthritis and Induces Proinflammatory Cytokine Production and Th17 Cell Generation. PLoS Biol. 2012;10(9):e1001395. <h3>Acknowledgement:</h3> This research was supported by the Basic Science Research&nbsp;Program&nbsp;through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (NRF-2017R1A2B4006015, NRF-2018R1D1A1A02050982 and NRF-2018R1A2B2006820) <h3><b>Disclosure of Interests</b>:</h3> None declared
SP0142 CASE 1 PRESENTER: A PATIENT WITH PERSISTING MONO/OLIGO-ARTHRITIS (EITHER AT START OR REMAINING AFTER TREATMENT OF POLY-ARTICULAR DISEASE)
Authors: William Tillett
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The varied clinical phenotypes of psoriatic arthritis present treatment challenges in clinical practice. The dominant phenotype represented in clinical trials is polyarthritis with little representation of oligoarticular or monoarticular disease. <h3>Objectives:</h3> To review the phenotypes of psoriatic disease and treatment of resistant oligo/monoarthritis in the context of a clinical case. <h3>Methods:</h3> Clinical case history <h3>Conclusion:</h3> The clinical phenotype of articular disease in psoriatic arthritis can evolve over time. There is limited data to inform the treatment of resistant oligo/monoarthritis <h3>Disclosure of Interests:</h3> William Tillett Grant/research support from: AbbVie, Celgene, and Lilly, Consultant for: AbbVie, Celgene, Lilly, Novartis, and Pfizer, Speakers bureau: Abbvie, Celgene, Lilly, Janssen, Novartis, UCB, and Pfizer
AB1134 IMPROVING THE STANDARDISATION OF DIAGNOSTIC LABORATORY TESTS FOR RF AND ACPA THROUGH THE ESTABLISHMENT OF A NEW INTERNATIONAL REFERENCE MATERIAL
Authors: Luisa de Jesus Saraiva, Peter Rigsby, Lucy Studholme
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rheumatoid arthritis is a debilitating chronic inflammatory disease. Its laboratory diagnosis relies mainly on testing for the presence of two groups of autoantibodies in patient's serum: rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Most RF assays are standardised against W1066, the WHO international standard rheumatoid arthritis serum established in 1968, or 64/002, the British Standard rheumatoid arthritis serum, which is the same material. Stocks of W1066 are becoming exhausted which triggered a decision by NIBSC and WHO to prepare a new standard preparation intended to replace W1066. <h3>Objectives</h3> Primarily, we have a responsibility to ensure the continuity of W1066 as a calibrator in RF agglutination-based assays. However, science has progressed and ACPA are now recognised as equally important to RF in the diagnosis of rheumatoid arthritis which is reflected in the ACR/EULAR 2010 classification guidelines. Therefore, we intend to assign the new standard values in international units to both RF and ACPA. In addition, some assays look at isotype-specific RF, so we will assess whether we can establish nominal values for the most common isotypes, IgM-RF and IgA-RF. <h3>Methods</h3> A pool of rheumatoid arthritis serum was prepared and dispensed into ampoules, lyophilised and sealed under an inert nitrogen atmosphere. An international collaborative study was organised with expert laboratories, including commercial kit manufacturers and medical laboratories, to assess the suitability of the new candidate standard and calibrate it against W1066. <h3>Results</h3> The results of the collaborative study will be used to propose a unitage to the new candidate standard in RF and ACPA for consideration at the WHO Expert Committee for Biological Standardisation. <h3>Conclusion</h3> Standardisation of diagnostic laboratory tests involves the development of a physical sample for each analyte. The use of these international reference standards as primary calibrants promotes the harmonisation of test results between different assays. Because the assays use a similar scale, their results are easily understood, which ultimately increases the impact of published research and clinical findings on our knowledge of the disease. <h3>References</h3> [1] WHO Expert Committee on Biological Standardization, sixty-seventh report. Geneva: World Health Organization; 2017 (WHO Technical Report Series; no. 1004). 2017 <h3>Disclosure of Interests</h3> None declared
PB2243 DOES ELTROMBOPAG CHANGE THE CHRONIC ITP COURSE IN CHILDREN, ESPECIALLY YOUNG?
Authors: M. Karwacki, P. Laguna, E. Celi, A. Klukowska, A. Adamowicz-Salach, K. Koch, M. Matysiak
Journal: HemaSphere (2019)

Background: Chronic immune thrombocytopenia (cITP) is a rare bleeding disorder with a high probability of spontaneous remission in childhood. Nevertheless, the course of cITP may be fatal in a given children. Currently available thrombopoietin receptor agonists may change the course of cITP and provide a hope for a successful therapy. Aims: To confirm an effectiveness of eltrombopag in children with complicated course of cITP. Methods: We present 6 case reports of patients aged from 4 to 14 years with complicated course of cITP treated in single, supraregional pediatric hematology center in Poland. Regardless rescue treatment with IVIGs and puls-steroids, the permanent 2-3 drugs immunosuppressive therapy implemented in all of them changed with the addition of eltrombopag only, resulted in genuine and long-standing rise in PLT number. Until a date of publication all patients have had been treated for a minimum 6 to a maximum 32 months. Results: Only one patient with milder course of cITP requires no treatment at the moment with harmless PLT count. The other 5 children are treated continuously: finally, 3 of them receive eltrombopag as monotherapy and another 2 in combination with immunosuppressive drugs (one low dose of steroids and one – steroid and mycophenolate mofetil). All 6 still have had required rescue therapy with IVIG or puls-steroids in some moments of eltrombopag therapy, especially in post infective count depletion, and 3 very often. None of children suffered from hepatotoxicity or cataract and bone fibrosis. Summary/Conclusion: Besides eltrombopag provides a valuable and effective option in cITP, the most important clinical issue during treatment is PLT count extreme fluctuations, mostly close to infective events, more profound and often required rescue support in young children. Insufficient and rigid dosing in young patients were due to indiscrete tablets available on Polish pharmacological market (no solution products).
AB0570 CLINICAL STUDY OF THE DISEASE ACTIVITY AND IMMUNE SCREENING OF PRIMARY SJOGREN’S SYNDROME
Authors: Yin Xufang, Zhang Mingxing, Ming Yan, LI Xiao-Feng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Objectives:</h3> To evaluate the change features of peripheral blood lymphocyte subsets and disease activity in patients with primary Sjogren's syndrome before and after treatment. <h3>Methods:</h3> A total of 30 patients with primary Sjogren's syndrome in the Department of Rheumatology from the Second Hospital of Shanxi Medical University from January 2016 to December 2018 were enrolled. According to the treatment time of patients, they were divided into baseline group, 0-3 months group, 3-6 months group, 6-12 months group, and the absolute counts of T, B, NK, Th1, Th2, Th17 and regulatory T cells(Tregs) in peripheral blood of patients before and during the treatment were measured by flow cytometry. The ratio of various cells to Tregs was calculated as well.The primary Sjogren's syndrome disease activity was assessed according to the Sjögren's syndrome disease activity index (ESSDAI) score and compared with 30 healthy people. <h3>Results:</h3> The Tregs counts in the disease group were significantly lower than those in the healthy control group (<i>p</i>&lt;0.05), and the ratio of proinflammatory lymphocytes to Tregs (Th17/Treg) was higher(<i>p</i>&lt;0.05).Tregs counts in peripheral blood of patients with primary Sjogren's syndrome has increased significantly after 3-month treatment,at the same time, the inflammatory index ESR was significantly lower <i>(p</i>&lt;0.05), the ESSDAI score was significantly lower (<i>p</i>&lt;0.05), and the high remission rate was maintained. However there was no statistically significant increase in Treg cell growth before treatment at 3-6 months and 6-12 months, (<i>p</i>&gt;0.05). <h3>Conclusion:</h3> The imbalance between pro-inflammatory lymphocytes and Tregs caused by the significant decrease of Tregs may be the cause of primary Sjogren's disease activity. We propose to promote the growth of Tregs and maintain the balance between pro-inflammatory lymphocytes and Tregs,which provides a new idea for disease relief of primary Sjogren's syndrome. <h3>Disclosure of Interests:</h3> None declared
Abstract 17567: Renal Denervation Therapy in Patients with Resistant Hypertension is Associated by Enhanced Urinary Sodium Excretion
Authors: Caroline Gisbertz, Christian Fatum, Klaas Franzen, Ansgar Leidinger, Tobias Graf, Frank Himmel, Frank Bode, Michael Reppel, Kai Mortensen, Heribert Schunkert, Joachim Weil
Journal: Circulation (2012)

Backround: Hypertensive patients (Pts) are characterized by increased sympathetic nerve activity (SNA) when compared with normotensive subjects. There is evidence that SNA results in increased reni...
SP0113 STEM CELL TRANSPLANTATION – ALL SCIENTIFIC QUESTIONS ANSWERED?
Authors: Jacob M. van Laar
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Hematopoietic stem cell transplantation (HSCT) currently is the only disease modifying treatment for patients with poor prognosis diffuse cutaneous systemic sclerosis (dcSSc) based on three controlled clinical trials (ASSIST, ASTIS, SCOT). Nevertheless uptake of this intensive treatment modality is slow in most countries, due to funding issues, lack of medical experience, and concerns over toxicities including the risk of transplant-related mortality (TRM). Over the years, safety of HSCT has improved and TRM has dropped due to more stringent patient selection and better supportive care. Nevertheless, dcSSc remains a high-risk condition for HSCT, and even a minimum degree of risk remains unavoidable. The decision to opt for HSCT therefore requires a thorough discussion of potential benefits and possible risks with a patient and their family and ultimately hinges on shared decision making and informed consent. Apart from such clinical issues there are still plenty of scientific questions to be answered. First, should HSCT be offered as first-line immunosuppressive or chemotherapy in high-risk patients, or is it better to reserve HSCT as salvage-therapy for those who failed a course of routine immunosuppression or i.v. pulse cyclophosphamide? And if so, on the basis of what criteria should treatment intensity be stepped up? Second, how can patient selection be optimised so as to avoid transplanting dcSSc patients with little chance of responding? Third, is there a window of opportunity where the immune system can be rebooted? Last but not least, how can potentially eligible dcSSc patients get access to HSCT? The latter may be the most (de)pressing one, as HSCT is only available in a small number of centres. Until efficacious disease-modifying drugs with a better risk-benefit ratio become available, HSCT will continue to be the only therapeutic option to reverse the disease course in dcSSc patients. <h3>Disclosure of Interests:</h3> Jacob M. van Laar Grant/research support from: Genentech, Consultant for: F. Hoffmann-La Roche
FRI0689 EFFECT OF AIR POLLUTION EXPOSURE ON DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS
Authors: Tommaso Schioppo, Isabella Scotti, Simona Iodice, Mirjam Hoxha, Orazio De Lucia, Antonella Murgo, Valentina Bollati, Francesca Ingegnoli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Environmental exposure (e.g. tobacco smoking, pollution) has been accepted to contribute in autoimmune diseases. Air pollution has been described to be a risk factor for developing rheumatoid arthritis (RA). Currently, RA disease remission is considered an achievable target in a significant proportion of patients. Nevertheless, diseases flares, that significantly contributes to damage progression and disability, remain unpredictable. Thus, factors able to potentially interfere on disease activity should be considered and assessed. <h3>Objectives</h3> The aim of our study is to evaluate the influence of particulate matter (PM) on disease activity and general health (GH) in patients with RA. <h3>Methods</h3> Consecutive patients with RA (ACR/EULAR Criteria 2010) resident in Lombardy (Italy) were enrolled. In each patient Disease Activity Score on 28 joints (DAS28), Simple Disease Activity Index (SDAI) and patients' GH were assessed. Daily PM concentrations, estimated by Regional Environmental Protection Agency at municipality resolution, were used to assign short-term exposure from day of visit back to 14 days. Continuous variables are expressed as mean±SD. Categorical variables are presented as absolute numbers and frequencies. Multivariable linear regression models were performed to identify the day of PM10 and PM2.5 independently associated with DAS28, GH and SDAI indices, adjusting for the variables significant at the univariate analysis. GH was log transformed to achieve normality of residuals. β coefficients were reported for 10 μg/m3 increments of PM concentrations. All statistical analyses were performed using SAS 9.4. <h3>Results</h3> 258 patients (age at visit 57.4±13.5 years, disease duration 16.2±12.1, female 80.2%, rheumatoid factor and/or anti-citrullinated peptide antibodies positivity 60.5%, smokers 15.5%, radiographic damage 41.5%) were enrolled in the study. Multivariable linear regression models were adjusted for radiographic damage, disease duration and age. Increases of PM2.5 and PM10 exposure (9 day before the visit) were significantly associated with worsening of DAS28, SDAI and GH (table below). PM concentrations in days other than 9 days before were significantly associated with disease activity and GH. <h3>Conclusion</h3> In our cohort, PM10 and PM2.5 exposure seems to influence RA disease activity with a lag period that can last until 9 days before the visit. Nevertheless, the association between day-to-day PM changes and disease activity do not confirm causation. Further studied are required to evaluate the influence of air pollution on RA activity. <h3>Disclosure of Interests</h3> None declared
Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer
Authors: Christopher J. Halbrook, Corbin Pontious, Ilya Kovalenko, Laura Lapienyte, Stephan Dreyer, Ho-Joon Lee, Galloway Thurston, Yaqing Zhang, Jenny Lazarus, Peter Sajjakulnukit, Hanna S. Hong, Daniel M. Kremer, Barbara S. Nelson, Samantha Kemp, Li Zhang, David Chang, Andrew Biankin, Jiaqi Shi, Timothy L. Frankel, Howard C. Crawford, Jennifer P. Morton, Marina Pasca di Magliano, Costas A. Lyssiotis
Journal: Cell Metabolism (2019)
THU0041 MESENCHYMAL STEM CELLS OF DIFFERENT ORIGINS EXHIBIT UNIQUE RESPONSES TO DIFFERENT INFLAMMATORY STIMULI
Authors: Blaž Burja, Ariana Barlič, Andreja Erman, Matija Tomsic, Katjuša Mrak-Poljšak, Snežna Sodin-Šemrl, Katja Lakota
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Mesenchymal stromal/stem cell (MSC) - based therapies represent promising avenues for treatment of various inflammatory and autoimmune diseases. Currently, a variety of fetal and adult tissues represent a good source of MSC, however further characterization of their effects, especially in an inflammatory environment, is needed. <h3>Objectives:</h3> Firstly, to characterize MSC from different origins, namely bone marrow (BM), adipose tissue (AT) and umbilical cord (UC), after stimulation with TNFα, IL-1β and serum amyloid A (SAA). Secondly, to determine the effects of MSC secretome on migration, proliferation and apoptosis of lung fibroblasts. <h3>Methods:</h3> BM-, AT- or UC-MSC were isolated each from 3 healthy donors. The expression and secretion of analytes were studied in each cell type at basal level and followingTNFα- (1 ng/ml), IL-1β- (1 ng/ml) and SAA- (12 µg/ml) stimulation using qPCR (SDF, CCL5, VCAM, PDE, PGC, IDO, VEGF, IGF) and Luminex technology (IL-6, IL8, MCP-1, ICAM, CH3L1, MMP1, MMP3, tenascin, uPA, HGF, VEGF), respectively. Normal healthy lung fibroblasts (NHLF) were used in the wound scratch assay and treated for 24h with 20% of MSC-conditioned media. For evaluation of BM-, AT- and UC conditioned media effects on proliferative and apoptotic activity, Ki-67-immunolabeled mitotic cells and caspase-3-immunolabeled cells were counted using fluorescence microscopy. <h3>Results:</h3> Treatment of MSC with pro-inflammatory cytokines increased mRNA levels of SDF, CCL5, VCAM1, PGC and IDO, while levels of PDE-5A were down-regulated. The greatest increase in expression was observed in TNFα-stimulated MSCs, namely of two immunomodulatory molecules, CCL5 and IDO in AT-MSC (4396- and 928-fold change increase respectively). Secretome analysis showed highest secretion levels of IL-6, IL-8 and MCP1 after IL-1β-activation in all 3 tissue sources. AT- and BM-derived conditioned media increased NHLF scratch closure, while UC-MSC decreased it. In non-inflammatory conditions, UC-, BM- and AT- MSCs conditioned media decreased the number of mitotic events in NHLF by an average of 40%. Importantly, only the conditioned medium derived from inflammatory cytokine-treated AT- and BM-MSC significantly decreased the mitotic rate of NHLF (p&lt;0.01). The number of apoptotic cells increased 3- to 8-fold after treatment with all MSC conditioned media, with UC-MSC showing the highest effect (p&lt;0.01). <h3>Conclusion:</h3> Our results highlight specific roles of MSC from different tissue origins, as well as their response to environmental inflammatory stimuli and suggest that source selection might be critical for the success of treatment approaches in different diagnoses. <h3>Disclosure of Interests:</h3> None declared
AB1006 THE CLINICAL SPECTRUM OF TWO HETEROZYGOUS MUTATIONS IN THE MVK GENE CONFIRMING HYPERIMMUNOGLOBULIN D SYNDROME
Authors: Dragana Lazarevic, Jelena Vojinovic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Autoinflammatory syndromes represent the wide spectrum of rare diseases (associated with genetic disturbances) characterized by the presence of chronic or recurrent systemic inflammation with diverse clinical presentation. <h3>Objectives</h3> We report a case report of child with confirmed two heterozygous mutations in the MVK gene with clinical features associated hyperimmunoglobulin D syndrome. <h3>Results</h3> We present girl with clinical symptoms starting just after birth when in the first days of life she was examined at gastroenterology department in Belgrade due to elevated parameters of inflammation, anemia, direct hyperbilirubinaemia, abdominal bloating and hepatosplenomegalia. Breastfeeding was discontinued due to galactosuria and lactose free diet was advised. Due to the maintenance of hepatomegaly, a detailed hematological, virusological and gastroenterological diagnostic testing was performed. Since liver biopsy has showed portal and lobular hepatitis with cholestasis without fibrosis she was on ursofalk treatment with partial response. At five months of age she started to have recurrent episodes of fever every month for few days with no associated infection, but always followed with digestive symptomatology (abdominal pain and abdominal flatulence) and elevation of inflammatory parameters. Despite antibiotics, episodes of fever continued to repeat twice monthly with accompanying occurrence of hypersalivation, small ulcers in the mouth, skin rash, cervical lymphadenopathy, hepatosplenomegaly, abdominal pain and abdominal bloating with elevated inflammatory markers. One year later she was admitted for the first time at our department and detailed differential diagnostic testing was performed. Clinical spectrum of presenting symptoms with specific phenotypic aspect (hypertelorismus and frontal bossing) were enough to suspect on autoinflammatory disease background (hyper IgD syndrome), but without IgG increase. Genetic testing have revealed presence of two heterozygous mutations ( heterozygous variant c.790del p.(Leu264Serfs*2) and heterozygous variant c.1129G&gt;A p.(Val377Ile) in the mevalonate kinase deficiency gene (MVK gene) confirming hyperimmunoglobulin D syndrome. Introduction of nonsteroidal antiinflammatory drug and corticosteroids have led to complete or partial remission during a fever episodes. As fever episodes continued on every two weeks we are about to start with donated fully-humanized protein (canakinumab), highly efficacious in fever episodes resolution by blocking interleukin-1 beta cytokine. <h3>Conclusion</h3> Diverse clinical manifestations of some patients with autoinflammatory diseases can provoke differential diagnostic and treatment dilemmas. Genetic testing is of great importance for establishing the final diagnosis and starting accurate treatment in order to prevent potential serious complications seen in these patients. <h3> Disclosure of Interests</h3> None declared