Deliverables
Report on the identification of auto-antigens associated with pathogenesis of RA
Agreement on a suitable strategy for testing of multiple tolerogenic therapies (UNEW, UCB)
Report on the core data set for characterisation of individuals at-risk for developing rheumatoid arthritis. In this part of WP2 the existing cohorts of individuals at-risk for development of RA from the RTCure partners will be analyzed and compared for their type of data acquisition in order to define an essential core data set for describing the “at-risk” state. This approach will comprise clinical parameters (such for instance the documentation of inflammatory arthralgia), laboratory parameters (such as ultrasensitive C-reactive protein and autoantibody titers against various autoantigens and peptides thereof, citrullinated proteins and other relevant antigenic protein modifications), and other relevant biomarkers (such as autoantibody profiles, protein biomarkers, RNA expression profiles, epigenetic profiles) as well as imaging parameters (such as subclinical synovitis, osteitis or tenosynovitis). Core parameters will be identified, which allow a comprehensive but also feasible description of the nature of the at-risk state in these individuals. In addition, novel more experimental parameters, in particular approaches coming from the immune-phenotyping of T and B cell populations done in WP3 and WP4 will be added to this parameter set, if shown to be relevant for a better characterization of the at-risk state. Importantly, the agreed key parameters will allow for harmonization of patient criteria that can be applied across clinical sites so as to ensure data comparability.
Compare at-risk individuals with recent-onset/early arthritis patients RTCure partners have already established well characterized cohorts of recent onset/early arthritis patients such as the TACERA, the Leiden Early Arthritis and the Scottish Early RA (SERA) cohorts, which provide an excellent possibility to compare the clinical, serologic and cellular features of patients who have recently moved into the inflammatory phase of the disease with those of imminent risk of developing the disease. Additional biobanks of recent onset/early arthritis patients from other RTCure partners (MUW, KI) provide valuable information of the serologic features of recent onset/early arthritis patients.
Screening and analysis of biological and clinical datasets generated within the project. Responsible partners LUMC and Pfizer.
Establishment of an algorithm for predicting the development of arthritis. The aim of this part is to develop a risk prediction model for development of RA, which is based on the parameters collected in the at-risk cohorts of the RTCure partners. Many of these cohorts contain longitudinal follow-ups, which allow to evaluate which of the at-risk individuals developed RA and which one remained in the at-risk stage. A particular focus will be drawn on parameters which predict progression to RA in several different cohorts. In addition, additive risk prediction by using several different parameters such as combination of clinical, laboratory and imaging parameters will be addressed.
Clinical trial ARIAA Midterm recruitment report (UKER, BMS)
Establishment of key risk predictors for the transition from the at-risk status to clinical arthritis (UA or RA). Core data sets extracted from existing cohorts in the first part of WP2 will be evaluated for their role in predicting the risk to progress from the at-risk state to the clinical state of arthritis (either undifferentiated arthritis or rheumatoid arthritis).
Definition of the optimal participant population(s) for clinical studies of tolerogenic interventions (UKER and UQ). The target population is critical for testing tolerogenic therapies and will be a topic for ongoing debate among WP6 members, with input from WPs 1 and 2 in particular.
Status on ongoing clinical trials in RTCure. Including: First study subject approvals package (ASCARA, ICosRA, APPIPRA), All approval package (ICosRA and APIPPRA), Midterm recruitment report (ICosRA, APIPPRA)
Set up external website with a RTCure logo and an internal communication platform where partners can store and share data and information and communicate about publications.
Build a multidisciplinary task force with expertise on biology, statistics, database management, including clinicians and ethicists.
Arrange thematic workshops in collaboration with the other WPs. Approximately one every year.
Publications
Author(s): 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
Published in: Arthritis Research & Therapy, Issue 20/1, 2018, ISSN 1478-6362
DOI: 10.1186/s13075-018-1586-z
Author(s): Fabian Stemmler, David Simon, Anna-Maria Liphardt, Matthias Englbrecht, Juergen Rech, Axel J Hueber, Klaus Engelke, Georg Schett, Arnd Kleyer
Published in: Annals of the Rheumatic Diseases, Issue 77/7, 2018, Page(s) 973-980, ISSN 0003-4967
DOI: 10.1136/annrheumdis-2017-212404
Author(s): Aline Bozec, Yubin Luo, Cecilia Engdahl, Camille Figueiredo, Holger Bang, Georg Schett
Published in: Arthritis Research & Therapy, Issue 20/1, 2018, ISSN 1478-6362
DOI: 10.1186/s13075-018-1527-x
Author(s): Daniela Sieghart, Alexander Platzer, Paul Studenic, Farideh Alasti, Maresa Grundhuber, Sascha Swiniarski, Thomas Horn, Helmuth Haslacher, Stephan Blüml, Josef Smolen, Günter Steiner
Published in: Frontiers in Immunology, Issue 9, 2018, ISSN 1664-3224
DOI: 10.3389/fimmu.2018.00876
Author(s): Tobias Alexander, Qingyu Cheng, Jens Klotsche, Laleh Khodadadi, Aderajew Waka, Robert Biesen, Bimba F. Hoyer, Gerd R. Burmester, Andreas Radbruch, Falk Hiepe
Published in: European Journal of Immunology, Issue 48/9, 2018, Page(s) 1573-1579, ISSN 0014-2980
DOI: 10.1002/eji.201847492
Author(s): Andrew P. Cope
Published in: Best Practice & Research Clinical Rheumatology, Issue 31/1, 2017, Page(s) 99-111, ISSN 1521-6942
DOI: 10.1016/j.berh.2017.08.005
Author(s): 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
Published in: Journal of Cellular and Molecular Medicine, Issue 22/9, 2018, Page(s) 4399-4409, ISSN 1582-1838
DOI: 10.1111/jcmm.13735
Author(s): 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, Mar
Published in: Nature, Issue 566/7744, 2019, Page(s) 344-349, ISSN 0028-0836
DOI: 10.1038/s41586-019-0896-x
Author(s): 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
Published in: Arthritis & Rheumatology, 2019, ISSN 2326-5191
DOI: 10.1002/art.40939
Author(s): Ulrike Steffen, Fabian T. Andes, Georg Schett
Published in: Current Protocols in Immunology, Issue 125/1, 2019, Page(s) e74, ISSN 1934-3671
DOI: 10.1002/cpim.74
Author(s): Lianne P. W. M. Lelieveldt, Hendy Kristyanto, Ger J. M. Pruijn, Hans Ulrich Scherer, René E. M. Toes, Kimberly M. Bonger
Published in: Molecular Pharmaceutics, Issue 15/12, 2018, Page(s) 5565-5573, ISSN 1543-8384
DOI: 10.1021/acs.molpharmaceut.8b00741
Author(s): 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
Published in: Arthritis Research & Therapy, Issue 20/1, 2018, ISSN 1478-6362
DOI: 10.1186/s13075-018-1691-z
Author(s): Eleni Kampylafka, David Simon, Isabelle d’Oliveira, Christina Linz, Veronika Lerchen, Matthias Englbrecht, Juergen Rech, Arnd Kleyer, Michael Sticherling, Georg Schett, Axel J. Hueber
Published in: Arthritis Research & Therapy, Issue 21/1, 2019, ISSN 1478-6362
DOI: 10.1186/s13075-019-1957-0
Author(s): 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
Published in: Arthritis Research & Therapy, Issue 20/1, 2018, ISSN 1478-6362
DOI: 10.1186/s13075-018-1620-1
Author(s): 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
Published in: Arthritis Research & Therapy, Issue 21/1, 2019, ISSN 1478-6362
DOI: 10.1186/s13075-019-1938-3
Author(s): 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
Published in: Annals of the Rheumatic Diseases, Issue 78/7, 2019, Page(s) 908-916, ISSN 0003-4967
DOI: 10.1136/annrheumdis-2018-214950
Author(s): 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
Published in: Annals of the Rheumatic Diseases, 2019, Page(s) annrheumdis-2019-215698, ISSN 0003-4967
DOI: 10.1136/annrheumdis-2019-215698
Author(s): 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
Published in: Arthritis & Rheumatology, Issue 71/10, 2019, Page(s) 1626-1633, ISSN 2326-5191
DOI: 10.1002/art.40920
Author(s): 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
Published in: Nature Communications, Issue 10/1, 2019, ISSN 2041-1723
DOI: 10.1038/s41467-019-08332-9
Author(s): 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
Published in: Journal of Cellular and Molecular Medicine, Issue 22/9, 2018, Page(s) 4399-4409, ISSN 1582-1838
DOI: 10.1111/jcmm.13735
Author(s): 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
Published in: Frontiers in Immunology, Issue 10, 2019, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.01367
Author(s): 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
Published in: The Journal of Immunology, Issue 201/12, 2018, Page(s) 3793-3803, ISSN 0022-1767
DOI: 10.4049/jimmunol.1701803
Author(s): 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
Published in: Frontiers in Immunology, Issue 10, 2019, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.02092
Author(s): 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
Published in: Experimental & Molecular Medicine, Issue 51/7, 2019, ISSN 1226-3613
DOI: 10.1038/s12276-019-0267-6
Author(s): Tamás Németh, Krisztina Futosi, Marcell Szabó, Petra Aradi, Takashi Saito, Attila Mócsai, Zoltán Jakus
Published in: Frontiers in Immunology, Issue 10, 2019, ISSN 1664-3224
DOI: 10.3389/fimmu.2019.00252
Author(s): P. Wehr, H. Purvis, S.‐C. Law, R. Thomas
Published in: Clinical & Experimental Immunology, Issue 196/1, 2019, Page(s) 12-27, ISSN 0009-9104
DOI: 10.1111/cei.13256
Author(s): 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
Published in: Annals of the Rheumatic Diseases, 2019, Page(s) annrheumdis-2018-214967, ISSN 0003-4967
DOI: 10.1136/annrheumdis-2018-214967
Author(s): 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
Published in: Journal of Clinical Medicine, Issue 8/5, 2019, Page(s) 630, ISSN 2077-0383
DOI: 10.3390/jcm8050630
Author(s): Karin Roos Ljungberg, Vijay Joshua, Thomas Skogh, Anders Eklund, C Magnus Sköld, Reza Karimi, Sven Nyrén, Anna Svärd, Anca I Catrina, Alf Kastbom
Published in: Rheumatology, 2019, ISSN 1462-0324
DOI: 10.1093/rheumatology/kez377
Author(s): Andrew P. Cope
Published in: Clinical Therapeutics, Issue 41/7, 2019, Page(s) 1299-1311, ISSN 0149-2918
DOI: 10.1016/j.clinthera.2019.04.014
Author(s): 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
Published in: Journal of Translational Medicine, Issue 17/1, 2019, ISSN 1479-5876
DOI: 10.1186/s12967-019-2128-4
