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RTCure SIGNED

Rheuma Tolerance for Cure

Total Cost €

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EC-Contrib. €

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Project "RTCure" data sheet

The following table provides information about the project.

Coordinator
KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Project website http://www.rtcure.com
 Total cost 13˙846˙865 €
 EC max contribution 6˙000˙000 € (43%)
 Programme 1. H2020-EU.3.1.7. (Innovative Medicines Initiative 2 (IMI2))
 Code Call H2020-JTI-IMI2-2016-09-two-stage
 Funding Scheme IMI2-RIA
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 1˙190˙000.00
2    ACADEMISCH ZIEKENHUIS LEIDEN NL (LEIDEN) participant 595˙000.00
3    Deutsches Rheuma-Forschungszentrum Berlin DE (Berlin) participant 465˙000.00
4    KING'S COLLEGE LONDON UK (LONDON) participant 465˙000.00
5    MEDIZINISCHE UNIVERSITAET WIEN AT (WIEN) participant 465˙000.00
6    THE UNIVERSITY OF BIRMINGHAM UK (BIRMINGHAM) participant 465˙000.00
7    UNIVERSITATSKLINIKUM ERLANGEN DE (ERLANGEN) participant 465˙000.00
8    UNIVERSITY OF GLASGOW UK (GLASGOW) participant 465˙000.00
9    UNIVERSITY OF NEWCASTLE UPON TYNE UK (NEWCASTLE UPON TYNE) participant 465˙000.00
10    THE UNIVERSITY OF QUEENSLAND AU (BRISBANE) participant 300˙000.00
11    ANOCCA AB SE (SODERTALJE) participant 240˙000.00
12    APITOPE INTERNATIONAL NV BE (DIEPENBEEK) participant 240˙000.00
13    SEMMELWEIS EGYETEM HU (BUDAPEST) participant 180˙000.00
14    BRISTOL-MYERS SQUIBB COMPANY CORP US (NEW YORK) participant 0.00
15    FONDAZIONE PER L ISTITUTO DI RICERCA IN BIOMEDICINA CH (BELLINZONA) participant 0.00
16    GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT LTD. UK (BRENTFORD) participant 0.00
17    JANSSEN PHARMACEUTICA NV BE (BEERSE) participant 0.00
18    PFIZER LIMITED UK (SANDWICH) participant 0.00
19    SANOFI-AVENTIS DEUTSCHLAND GMBH DE (FRANKFURT AM MAIN) participant 0.00
20    UCB BIOPHARMA SRL BE (BRUXELLES) participant 0.00

Map

 Project objective

In line with IMI2 goals for improved therapies and precision medicine, the aim of this proposal is to prevent and treat RA or its progression by inhibiting maturation/expansion of pathogenic autoimmune responses through immune tolerising treatments of subjects not only in early stages of joint inflammation (undifferentiated arthritis and early RA) but also in even earlier defined stages i.e. before onset of joint inflammation, when patients have arthralgia and/or bone loss, or sub-clinical stages of joint inflammation.

Today, no drugs are approved for these early phases of RA development, where symptoms such as pain and fatigue cause major loss of life quality and where successful interference would prevent onset of disease. Thus, an important part of our work will be to achieve a better understanding of this as yet unexplored phase of disease. In the proposed project we will develop and validate new methods to identify individuals at high risk for RA, tools to monitor disease progress and expand and further develop cohorts suitable for these purposes. Furthermore we will validate and standardise methods to monitor immune tolerance to be used in clinical trials for tolerising therapies for RA. The aim is thus to interfere with the specific immune reactions that contribute to RA symptoms in such a way that a specific and long-lasting therapeutic effect (ultimately a cure) is accomplished for a major proportion of RA patients and prevention of diseases is accomplished in individuals at high risk for RA.

Investigator-initiated as well as company-sponsored clinical trials in well stratified patient groups will be performed in collaboration with SMEs and/or contributing pharma companies and their immune effects studied using the same panel of biomarkers allowing for standardisation across protocols. Our ambition is also to disseminate our experiences from RA to other rheumatic and other immune-mediated diseases.

 Deliverables

List of deliverables.
Comparison of serologic features of at-risk individuals and recent onset arthritis patients Documents, reports 2020-04-14 16:13:06
Optimal participant population(s) for clinical studies of tolerogenic interventions Documents, reports 2020-04-14 16:13:06
Algorithm for predicting the development of arthritis Documents, reports 2020-04-14 16:13:06
Key risk predictors for the transition from the at-risk status to clinical arthritis Documents, reports 2020-04-14 16:13:06
ARIAA Midterm recruitment report Documents, reports 2020-04-14 16:13:06
Status on ongoing clinical trials in RTCure Documents, reports 2020-04-14 16:13:05
Arrange thematic workshops in collaboration with the other WPs Other 2020-04-14 16:13:05
Report on the core data set for characterisation of individuals at-risk for developing RA Documents, reports 2020-04-14 16:13:05
Build a multidisciplinary task force Websites, patent fillings, videos etc. 2020-04-14 16:13:05
Set up internal and external website with a RTCure logo Websites, patent fillings, videos etc. 2020-04-14 16:13:05
Screening and analysis of biological and clinical datasets Documents, reports 2020-04-14 16:13:05

Take a look to the deliverables list in detail:  detailed list of RTCure deliverables.

 Publications

year authors and title journal last update
List of publications.
2019 Rachel Spiering, Manon A. A. Jansen, Matthew J. Wood, Anshorulloh A. Fath, Oliver Eltherington, Amy E. Anderson, Arthur G. Pratt, Willem van Eden, John D. Isaacs, Femke Broere, Catharien M. U. Hilkens
Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis
published pages: , ISSN: 1479-5876, DOI: 10.1186/s12967-019-2128-4
Journal of Translational Medicine 17/1 2020-04-14
2019 Eliana Goncalves-Alves, Victoria Saferding, Christopher Schliehe, Robert Benson, Mariola Kurowska-Stolarska, Julia Stefanie Brunner, Antonia Puchner, Bruno K. Podesser, Josef S. Smolen, Kurt Redlich, Michael Bonelli, James Brewer, Andreas Bergthaler, Günter Steiner, Stephan Blüml
MicroRNA-155 Controls T Helper Cell Activation During Viral Infection
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.01367
Frontiers in Immunology 10 2020-04-14
2019 Theresa Kissel, Karin Anna van Schie, Lise Hafkenscheid, Anders Lundquist, Heidi Kokkonen, Manfred Wuhrer, Tom WJ Huizinga, Hans Ulrich Scherer, René Toes, Solbritt Rantapää-Dahlqvist
On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis
published pages: annrheumdis-2019, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2019-215698
Annals of the Rheumatic Diseases 2020-04-14
2019 Lise Hafkenscheid, Emma Moel, Irene Smolik, Stacey Tanner, Xiaobo Meng, Bas C. Jansen, Albert Bondt, Manfred Wuhrer, Tom W. J. Huizinga, Rene E. M. Toes, Hani El‐Gabalawy, Hans U. Scherer
N ‐Linked Glycans in the Variable Domain of IgG Anti–Citrullinated Protein Antibodies Predict the Development of Rheumatoid Arthritis
published pages: 1626-1633, ISSN: 2326-5191, DOI: 10.1002/art.40920
Arthritis & Rheumatology 71/10 2020-04-14
2019 David Simon, Arnd Kleyer, Sara Bayat, Koray Tascilar, Eleni Kampylafka, Timo Meinderink, Louis Schuster, Ramona Petrov, Anna-Maria Liphardt, Juergen Rech, Georg Schett, Axel J. Hueber
Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-019-1938-3
Arthritis Research & Therapy 21/1 2020-04-14
2019 Tamás Németh, Krisztina Futosi, Marcell Szabó, Petra Aradi, Takashi Saito, Attila Mócsai, Zoltán Jakus
Importance of Fc Receptor γ-Chain ITAM Tyrosines in Neutrophil Activation and in vivo Autoimmune Arthritis
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.00252
Frontiers in Immunology 10 2020-04-14
2019 Karin Roos Ljungberg, Vijay Joshua, Thomas Skogh, Anders Eklund, C Magnus Sköld, Reza Karimi, Sven Nyrén, Anna Svärd, Anca I Catrina, Alf Kastbom
Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis
published pages: , ISSN: 1462-0324, DOI: 10.1093/rheumatology/kez377
Rheumatology 2020-04-14
2019 Rochelle D. Vergroesen, Linda M. Slot, Barbera D. C. van Schaik, Marvyn T. Koning, Theo Rispens, Antoine H. C. van Kampen, René E. M. Toes, Hans U. Scherer
N-Glycosylation Site Analysis of Citrullinated Antigen-Specific B-Cell Receptors Indicates Alternative Selection Pathways During Autoreactive B-Cell Development
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.02092
Frontiers in Immunology 10 2020-04-14
2018 Anna Neumann, Judith Haschka, Arnd Kleyer, Louis Schuster, Matthias Englbrecht, Andreas Berlin, Camille P. Figueiredo, David Simon, Christian Muschitz, Roland Kocijan, Heinrich Resch, Jürgen Rech, Georg Schett
Cortical bone loss is an early feature of nonradiographic axial spondyloarthritis
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-018-1620-1
Arthritis Research & Therapy 20/1 2020-04-14
2019 Kaja Eriksson, Guozhong Fei, Anna Lundmark, Daniel Benchimol, Linkiat Lee, Yue O. O. Hu, Anna Kats, Saedis Saevarsdottir, Anca Irinel Catrina, Björn Klinge, Anders F. Andersson, Lars Klareskog, Karin Lundberg, Leif Jansson, Tülay Yucel-Lindberg
Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis
published pages: 630, ISSN: 2077-0383, DOI: 10.3390/jcm8050630
Journal of Clinical Medicine 8/5 2020-04-14
2019 Esperanza Perucha, Rossella Melchiotti, Jack A Bibby, Wing Wu, Klaus Stensgaard Frederiksen, Ceri A. Roberts, Zoe Hall, Gaelle LeFriec, Kevin A. Robertson, Paul Lavender, Jens Gammeltoft Gerwien, Leonie S. Taams, Julian L. Griffin, Emanuele de Rinaldis, Lisa G. M. van Baarsen, Claudia Kemper, Peter Ghazal, Andrew P. Cope
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-08332-9
Nature Communications 10/1 2020-04-14
2019 Meng Sun, Bence Rethi, Akilan Krishnamurthy, Vijay Joshua, Alexandra Circiumaru, Aase Haj Hensvold, Elena Ossipova, Caroline Grönwall, Yanying Liu, Marianne Engstrom, Sergiu Bogdan Catrina, Johanna Steen, Vivianne Malmstrom, Lars Klareskog, Camilla Svensson, Caroline Ospelt, Heidi Wähämaa, Anca Irinel Catrina
Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts
published pages: annrheumdis-2018, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2018-214967
Annals of the Rheumatic Diseases 2020-04-14
2018 Lianne P. W. M. Lelieveldt, Hendy Kristyanto, Ger J. M. Pruijn, Hans Ulrich Scherer, René E. M. Toes, Kimberly M. Bonger
Sequential Prodrug Strategy To Target and Eliminate ACPA-Selective Autoreactive B Cells
published pages: 5565-5573, ISSN: 1543-8384, DOI: 10.1021/acs.molpharmaceut.8b00741
Molecular Pharmaceutics 15/12 2020-04-14
2018 David Simon, Arnd Kleyer, Francesca Faustini, Matthias Englbrecht, Judith Haschka, Andreas Berlin, Sebastian Kraus, Axel J. Hueber, Roland Kocijan, Michael Sticherling, Juergen Rech, Georg Schett
Simultaneous quantification of bone erosions and enthesiophytes in the joints of patients with psoriasis or psoriatic arthritis - effects of age and disease duration
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-018-1691-z
Arthritis Research & Therapy 20/1 2020-04-14
2019 P. Wehr, H. Purvis, S.‐C. Law, R. Thomas
Dendritic cells, T cells and their interaction in rheumatoid arthritis
published pages: 12-27, ISSN: 0009-9104, DOI: 10.1111/cei.13256
Clinical & Experimental Immunology 196/1 2020-04-14
2019 Andrew P. Cope
Considerations for Optimal Trial Design for Rheumatoid Arthritis Prevention Studies
published pages: 1299-1311, ISSN: 0149-2918, DOI: 10.1016/j.clinthera.2019.04.014
Clinical Therapeutics 41/7 2020-04-14
2019 Eleni Kampylafka, David Simon, Isabelle d’Oliveira, Christina Linz, Veronika Lerchen, Matthias Englbrecht, Juergen Rech, Arnd Kleyer, Michael Sticherling, Georg Schett, Axel J. Hueber
Disease interception with interleukin-17 inhibition in high-risk psoriasis patients with subclinical joint inflammation—data from the prospective IVEPSA study
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-019-1957-0
Arthritis Research & Therapy 21/1 2020-04-14
2018 Janka Zsófia Csepregi, Anita Orosz, Erik Zajta, Orsolya Kása, Tamás Németh, Edina Simon, Szabina Fodor, Katalin Csonka, Balázs L. Barátki, Dorottya Kövesdi, You-Wen He, Attila Gácser, Attila Mócsai
Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form
published pages: 3793-3803, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1701803
The Journal of Immunology 201/12 2020-04-14
2019 Michael Bonelli, Karolina Dalwigk, Alexander Platzer, Isabel Olmos Calvo, Silvia Hayer, Birgit Niederreiter, Johannes Holinka, Florian Sevelda, Thomas Pap, Günter Steiner, Giulio Superti-Furga, Josef S. Smolen, Hans P. Kiener, Thomas Karonitsch
IRF1 is critical for the TNF-driven interferon response in rheumatoid fibroblast-like synoviocytes
published pages: , ISSN: 1226-3613, DOI: 10.1038/s12276-019-0267-6
Experimental & Molecular Medicine 51/7 2020-04-14
2019 Arieke Suzanna Berendina Kampstra, Jacqueline Stephanie Dekkers, Mikhail Volkov, Annemarie L Dorjée, Lise Hafkenscheid, Ayla C Kempers, Myrthe van Delft, Theresa Kissel, Sanne Reijm, George M C Janssen, Peter A van Veelen, Holger Bang, Tom W J Huizinga, Leendert A Trouw, Diane van der Woude, René E M Toes
Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
published pages: 908-916, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2018-214950
Annals of the Rheumatic Diseases 78/7 2020-04-14
2019 Kristyna Hradilkova, Patrick Maschmeyer, Kerstin Westendorf, Heidi Schliemann, Olena Husak, Anne Sae Lim Stuckrad, Tilmann Kallinich, Kirsten Minden, Pawel Durek, Joachim R. Grün, Hyun‐Dong Chang, Andreas Radbruch
Regulation of Fatty Acid Oxidation by Twist 1 in the Metabolic Adaptation of T Helper Lymphocytes to Chronic Inflammation
published pages: , ISSN: 2326-5191, DOI: 10.1002/art.40939
Arthritis & Rheumatology 2020-04-14
2019 Thomas Wohlfahrt, Simon Rauber, Steffen Uebe, Markus Luber, Alina Soare, Arif Ekici, Stefanie Weber, Alexandru-Emil Matei, Chih-Wei Chen, Christiane Maier, Emmanuel Karouzakis, Hans P. Kiener, Elena Pachera, Clara Dees, Christian Beyer, Christoph Daniel, Kolja Gelse, Andreas E. Kremer, Elisabeth Naschberger, Michael Stürzl, Falk Butter, Michael Sticherling, Susetta Finotto, Alexander Kreuter, Mark H. Kaplan, Astrid Jüngel, Steffen Gay, Stephen L. Nutt, David W. Boykin, Gregory M. K. Poon, Oliver Distler, Georg Schett, Jörg H. W. Distler, Andreas Ramming
PU.1 controls fibroblast polarization and tissue fibrosis
published pages: 344-349, ISSN: 0028-0836, DOI: 10.1038/s41586-019-0896-x
Nature 566/7744 2020-04-14
2018 Anita Fischer, Shahla Abdollahi-Roodsaz, Christina Böhm, Birgit Niederreiter, Brigitte Meyer, Anthony C. Y. Yau, Erik Lönnblom, Leo A. B. Joosten, Marije Koenders, Christian H. K. Lehmann, Diana Dudziak, Gerhard Krönke, Rikard Holmdahl, Günter Steiner
The involvement of Toll-like receptor 9 in the pathogenesis of erosive autoimmune arthritis
published pages: 4399-4409, ISSN: 1582-1838, DOI: 10.1111/jcmm.13735
Journal of Cellular and Molecular Medicine 22/9 2020-04-14
2018 Aline Bozec, Yubin Luo, Cecilia Engdahl, Camille Figueiredo, Holger Bang, Georg Schett
Abatacept blocks anti-citrullinated protein antibody and rheumatoid factor mediated cytokine production in human macrophages in IDO-dependent manner
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-018-1527-x
Arthritis Research & Therapy 20/1 2020-04-14
2018 Fabian Stemmler, David Simon, Anna-Maria Liphardt, Matthias Englbrecht, Juergen Rech, Axel J Hueber, Klaus Engelke, Georg Schett, Arnd Kleyer
Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures
published pages: 973-980, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2017-212404
Annals of the Rheumatic Diseases 77/7 2020-04-14
2018 Tobias Alexander, Qingyu Cheng, Jens Klotsche, Laleh Khodadadi, Aderajew Waka, Robert Biesen, Bimba F. Hoyer, Gerd R. Burmester, Andreas Radbruch, Falk Hiepe
Proteasome inhibition with bortezomib induces a therapeutically relevant depletion of plasma cells in SLE but does not target their precursors
published pages: 1573-1579, ISSN: 0014-2980, DOI: 10.1002/eji.201847492
European Journal of Immunology 48/9 2020-04-14
2018 Cecilia Engdahl, Albert Bondt, Ulrike Harre, Jasmin Raufer, René Pfeifle, Alessandro Camponeschi, Manfred Wuhrer, Michaela Seeling, Inga-Lill Mårtensson, Falk Nimmerjahn, Gerhard Krönke, Hans U. Scherer, Helena Forsblad-d’Elia, Georg Schett
Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women
published pages: , ISSN: 1478-6362, DOI: 10.1186/s13075-018-1586-z
Arthritis Research & Therapy 20/1 2020-04-14
2018 Daniela Sieghart, Alexander Platzer, Paul Studenic, Farideh Alasti, Maresa Grundhuber, Sascha Swiniarski, Thomas Horn, Helmuth Haslacher, Stephan Blüml, Josef Smolen, Günter Steiner
Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2018.00876
Frontiers in Immunology 9 2020-04-14
2017 Andrew P. Cope
Emerging therapies for pre-RA
published pages: 99-111, ISSN: 1521-6942, DOI: 10.1016/j.berh.2017.08.005
Best Practice & Research Clinical Rheumatology 31/1 2020-04-14

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