Welcome to the RELENT newsletter!
With this fifth issue of our bi-annual newsletter we would like to update you about the RELENT project - its participants and objectives, its progress and results.
RELENT in a nutshell
What is RELENT?
RELENT is a research project funded by the European Union's Horizon 2020 Framework Programme for Research and Innovation. RELENT stands for RELapses prevENTion in chronic autoimmune disease: common mechanisms and co-morbidities.
The RELENT Consortium is a multidisciplinary group of scientists and clinical investigators whose goal it is to develop individualized treatments for chronic autoimmune diseases, such as rheumatoid arthritis and vasculitis.
Note from Prof. Renate Kain, M.D., Ph.D., Project Coordinator
Severe autoimmune and inflammatory diseases currently need to be treated with long-term immunosuppressive drugs that have significant side effects. Despite this, the outcome for individual patients varies considerably. We currently have no means of distinguishing from the outset which patients will suffer from frequent relapses of their disease – and therefore need intensive early treatment – from those who will not. The RELENT project will apply an entirely novel approach to systematically define common disease mechanisms in autoimmunity, involving a fast and high throughput discovery and validation process. By combining clinical and serological data with genetic and transcriptomic signatures to unravel the molecular mechanisms that determine disease outcome, we will be able to develop customised health care for people suffering from autoimmune disorders.
RELENT aims to shed light on the course and mechanisms of diseases, such as rheumatoid arthritis and vasculitis, and to develop improved diagnostics and intervention strategies with the expected impact of delaying the onset of chronic autoimmune diseases.
The work in the project is divided into six areas:
- Identification of common pathways that influence disease outcome and response to treatment and infection (work package 1)
- Identification of protein signatures that predict disease outcome and anticipate infective complications (work package 2)
- The ageing immune system and its relation to the development of autoimmunity and co-morbidities (work package 3)
- Pathogenic role of T cells and their interactions with myeloid cells (work package 4)
- Dissemination, exploitation and communication (work package 5)
- Project Management (work package 6)
The project started on November 1, 2015 with a project duration of 54 months.
Main project objectives of RELENT
RELENT´s overall mission is to
- understand common mechanisms of diseases and their relevance in co-morbidities thereby transforming the clinical outcome for patients with severe autoimmune and inflammatory diseases, and to
- provide the scientific underpinning by closing the knowledge gap in common mechanisms of disease. This should result in a more individualized and thus safer and more effective management for severe autoimmune and inflammatory disease.
The RELENT project will analyse data from a variety of measurements (clinical, serological, genetic, transcriptomic) and thus develop new biomarkers for these diseases. These should allow the tailoring of the most efficacious treatment to each patient with a chronic autoimmune disease.
News and Events
Over the course of the half year a number of events took place.
RELENT 5th General Assembly Meeting and 7th Steering Committee Meeting
The 5th RELENT meeting as well as 7th steering committee meeting took place in Nice, France from the 1st to the 4th of September 2019.
During the meeting in Nice progress updates of the various work packages were presented and future plans were discussed. Especially since the final stage of the project is approaching ideas were shared to help out each other to be able to reach milestones and deliverables. Overall the progress looks great and additional new findings could be an interesting starting point for a follow up program of the RELENT consortium.
Training workshop on iPSC cells
One of the major concerns in science nowadays is a lack of reproducibility in experimental methods. Especially with challenging culture techniques like iPSC and embryoid body culture for targeted cell differentiation it is of utmost importance to share and harmonise protocols within our consortium.
To address this topic William Jiemy from UMCG and Stefan Schulz from MUW visited the facility of Phenocell in Grasse from 23rd to 26th April 2019 to learn the established methods from their experienced staff in a hands-on workshop. The curriculum included basic handling techniques as well as more intricate protocols like the generation and long-term culture of embryoid bodies. Another core element of the workshop were quality control measures to ensure that iPSC quality and purity does not decrease over an extended period of culture. Additionally, there was the opportunity to share and discuss our previous experiences with iPSC culture.
The workshop proved to be a valuable event to harmonise the protocols for iPSC and embryoid body culture and will have a great impact on reliability and reproducibility of experiments.
Meet the team @ University Hospital Bonn, Germany
The Institute of Experimental Immunology (IEI) was founded in 2002. It is situated on the medical Campus of the Friedrich-Wilhelms-Universität Bonn, one of only eleven Universities of Excellence in Germany and one of two in North Rhine-Westphalia. Since 2009, Prof. Christian Kurts has been the Director of the IEI. He is known for publications in the fields of cross-presentation and immune tolerance as well as for his work on the function of dendritic cells in a variety of organs, with a particular focus on the urogenital tract and kidneys. In 2012, he shared the prestigious Gottfried Wilhelm Leibnitz Prize with Gunther Hartmann for their “Seminal discoveries concerning the mode of action of the body’s endogenous defense systems.” This award, also known as the German Nobel Prize, is the highest scientific honor in Germany.
The scientific mission of the IEI is to understand the molecular and cellular mechanisms controlling the immune response in a local fashion to develop either into immunity or immune tolerance. Comprehensive knowledge of the physiological regulation of immune tolerance is required to understand the immuno-pathology of chronic inflammation after infection, autoimmunity and perhaps even failure of the immune response to eliminate tumors. Research groups at IEI also join forces to develop novel methods to modulate cell function within tissue using laser-assisted nanoparticle-mediated strategies. Ultimately, we intend to develop new strategies to modulate local immune responses for therapeutic purposes. Prof. Christian Kurts is also involved within work package 4 entitled ‘Pathogenic role of T cells and their interactions with myeloid cells’. The overall purpose of this work package is to dissect the mechanisms by which leukocytes, in particular T cells, macrophages and DCs, and mediators they produce, control injury in experimental AAV. Specifically, this work package aims at :
- Defining the role of memory CD8+ cells and the potential contributions of MPO-specific T helper subsets to autoimmunity and injury in experimental AAV
- How T cell function is controlled by tissue macrophages and DC
- Define the role of Cathepsin S as a mediator to chronic inflammatory injury and its complications
For more information on the Institute of Experimental Immunology follow us on twitter
@IEI_Bonn or visit our website.
Meet the team @ Monash University, Australia
The Monash Autoimmune Kidney Disease and Vasculitis Research Group is a group of Physician-scientists and researchers working to improve outcomes for people with kidney disease, especially those with autoimmune vasculitis, by new and better treatments. By understanding disease and examining new therapeutic strategies and targets, we aim to improve care for people with these important conditions.
Caption: Glomerulonephritis associated with autoimmune vasculitis is often severe and rapidly progressive
Current treatments for rapidly progressive forms of glomerulonephritis – of which the most common is ANCA-associated vasculitis – are inadequate. Their effectiveness is incomplete, and they have undesirable metabolic and immune side effects that lead to significant morbidity and can even cause death. Therefore, in these diseases there is a substantial unmet clinical need for new and better treatments. The strategy that underpins the approach to our research is to understand the fundamental biology of autoimmune vasculitis and renal disease so that more targeted therapies can be used in these conditions. Current studies are examining a variety of immunomodulatory strategies in experimental ANCA-associated vasculitis.
The group has been central in establishing the role of cell-mediated immunity in severe forms of glomerulonephritis, especially those due to autoimmune vasculitis. In these diseases, anti-neutrophil cytoplasmic antibodies (ANCA) bind to and activate neutrophils that lodge in vulnerable microvascular beds and induce injury. The group has contributed to our understanding of direct ANCA and neutrophil mediated injury. We have also had an interest in defining the subsequent and important antigen specific cell-mediated effector responses, steps that involve deposition of the autoantigen in target tissues and its recognition by effector antigen-specific CD4+ and CD8+ T cells, with resultant microvascular injury. More recently, the group has used autoimmune renal diseases as archetypal autoimmune diseases to understand the fundamental biology critical to autoimmunity in general.
Current research themes of the group include:
- The fundamental basis of loss of tolerance in autoimmune vasculitis
- The effects of infections on immune kidney disease and vasculitis
- Defining the key epitopes in antigens that cause autoimmune kidney disease
- Immunomodulatory pathways, including antigen specific pathways as potential new treatments for disease
- The role of neutrophils in effector injury and in loss of tolerance
Within the RELENT consortium Professor Richard Kitching, with Dr Maliha Alikhan make significant contributions to work package 3 “The ageing immune system and its relation to the development of autoimmunity and co-morbidities” and work package 4 “Pathogenic role of T cells and their interactions with myeloid cells.” Some of our members are clinician-scientists, and the research group has close links with the Monash Health Departments of Nephrology and with Clinical and Diagnostic Immunology, including the Monash Vasculitis Clinic. We have a long and established track record in training scientists and clinician-scientists, with multiple researchers trained within the group going on to secure independent funding and direct their own research program. Recently, members of the group were instrumental in establishing the Australian and New Zealand Vasculitis Society (ANZVASC).
The group has, in the last 3 years, published work in key journals including Nature, Nature Communications, The Journal of the American Society of Nephrology and Kidney International. The group’s recent publications can be accessed here.
For more information on the activities of the group, follow laboratory members on twitter (@Kitchinglab @malihaalikhan @KimMareeOSulli1 or @nephrologista) or go to the website.
RELENT website and Social Media
Find out more about the diseases
Are you interested in knowing more about the diseases that are the focus of the RELENT project? On our website you can find links to excellent on-line resources with a wealth of accurate and up to date information, specifically written for patients and the general public. They describe what is known about the causes of the diseases, how they are diagnosed and treated. You will also find the answers to many frequently asked questions and many other resources to support patients and their families.
Upcoming meetings and events
The 6th and final RELENT General Assembly Meeting will take place in Vienna, Austria in March 2020. Simultaneously an open workshop/seminar shall take place.