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Rheuma Tolerance for Cure

Deliverables

Set up internal and external website with a RTCure logo

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

Build a multidisciplinary task force with expertise on biology, statistics, database management, including clinicians and ethicists.

Report on the core data set for characterisation of individuals at-risk for developing RA

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.

Comparison of serologic features of at-risk individuals and recent onset arthritis patients

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

Screening and analysis of biological and clinical datasets generated within the project. Responsible partners LUMC and Pfizer.

Algorithm for predicting the development of arthritis

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.

ARIAA Midterm recruitment report

Clinical trial ARIAA Midterm recruitment report (UKER, BMS)

Key risk predictors for the transition from the at-risk status to clinical arthritis

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).

Optimal participant population(s) for clinical studies of tolerogenic interventions

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

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)

Arrange thematic workshops in collaboration with the other WPs

Arrange thematic workshops in collaboration with the other WPs. Approximately one every year.

Publications

Biomechanical properties of bone are impaired in patients with ACPA-positive rheumatoid arthritis and associated with the occurrence of fractures

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

Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis

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

Emerging therapies for pre-RA


Published in: ISSN 1521-6942
DOI: 10.1016/j.berh.2017.08.005

The involvement of Toll-like receptor 9 in the pathogenesis of erosive autoimmune arthritis

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

PU.1 controls fibroblast polarization and tissue fibrosis

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

Generation and Analysis of Human and Murine Osteoclasts

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

Sequential Prodrug Strategy To Target and Eliminate ACPA-Selective Autoreactive B Cells

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

Cortical bone loss is an early feature of nonradiographic axial spondyloarthritis


Published in: ISSN 1478-6362
DOI: 10.1186/s13075-018-1620-1

Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification

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

On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis

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

The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells

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

The involvement of Toll‐like receptor 9 in the pathogenesis of erosive autoimmune arthritis

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

MicroRNA-155 Controls T Helper Cell Activation During Viral Infection

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

Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form

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

N-Glycosylation Site Analysis of Citrullinated Antigen-Specific B-Cell Receptors Indicates Alternative Selection Pathways During Autoreactive B-Cell Development

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

Importance of Fc Receptor γ-Chain ITAM Tyrosines in Neutrophil Activation and in vivo Autoimmune Arthritis

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

Dendritic cells, T cells and their interaction in rheumatoid arthritis


Published in: ISSN 0009-9104
DOI: 10.1111/cei.13256

Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts

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

Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis

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

Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis

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

Considerations for Optimal Trial Design for Rheumatoid Arthritis Prevention Studies

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

Targeting of tolerogenic dendritic cells to heat-shock proteins in inflammatory arthritis

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