RELENT NEWS | Issue 2 | 12/2017
 
 
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RELENT NEWS | Issue 2 | 12/2017
 
 

Welcome to the RELENT newsletter!

With this second issue of our bi-annual newsletter we would like to update you about the RELENT project - its participants and objectives, its progress and results.

Contents

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 in both females and males affected by them.

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 last year a number of members of the RELENT consortium have been in the news.

Prof Albert Heck awarded the Spinoza Prize

We would like to extend our congratulations to Albert Heck, Professor of Biomolecular Mass Spectrometry and Proteomics at Utrecht University, who has been awarded the prestigious Spinoza Prize by the Netherlands Organisation for Scientific Research (NWO). This award, also known as the Nobel Prize of the Low Countries, is the highest scientific honour in the Netherlands.  The prize comes with an award of €2.5 million to be spent on research of the winners choosing.
Prof. Heck and his team are bringing their vast experience in proteomics into the RELENT consortium, to analyze therapeutic and pathogenic antibodies in immune-mediated disease and identify proteins in the blood that can act as markers of disease activity or clinical outcome.

Albert Heck Spinoza Prize

Dr Joshua Ooi announced 2018 Al & Val Rosenstrauss Research Fellow

Dr Joshua Ooi, a Senior Research Fellow and investigator on RELENT at Monash University in the team led by Prof Richard Kitching,  has been awarded the 2018 Al & Val Rosenstrauss Fellowship. This prestigious 4-year Career Development Fellowship, awarded by the Rebecca L. Cooper Medical Research Foundation, is targeted at earlier career researchers, who show potential to be stars of the future and who are building credentials for a long career in research. The award will further support Dr Ooi’s innovative research, aimed at developing therapies to specifically treat the cause of ANCA associated vasculitides without affecting protective immunity.

RELENT@ American Society of Nephrology Meeting

Prof Hans-Joachim Anders, leader of the RELENT team at the Ludwig-Maximilians-Universität München, discussed advances in the treatment of kidney disease due to systemic lupus erythematosus at the annual meeting of the American Society of Nephrology (New Orleans, Oct 31-Nov 5 2017). Among the highlights of his talk, Prof. Anders presented cutting-edge work from his laboratory looking at chemokine inhibitors, a novel class of anti-inflammatory drugs, that have proved to be as effective as current standard of care in mouse models of lupus nephritis.  These new “smart” medicines target inflammation more selectively than conventional treatment, promising greater efficacy with fewer side effects.

A warm welcome to new members of the RELENT Team

David Just (left) has recently joined the RELENT team KTH Royal Institute of Technology. David is 3rd year PhD student in Prof Peter Nilsson’s lab where his research focus so far has been on the relationship between autoimmunity and psychiatric disorders. David has applied novel analytical techniques to investigate antibody signatures in schizophrenia and psychosis. As part of RELENT, David will implement these techniques in patients with ANCA-associated vasculitis, Giant Cell Arthritis and Polymyalgia Rheumatica, where the aim is to identify auto-antibody profiles associated with disease activity and response to treatment. This should facilitate the identification of novel therapeutic targets and personalize treatment.

Dr Karli Reiding has joined Prof Albert Heck’s RELENT team at Universiteit Utrecht. Dr Reiding is an expert in the glycomics/glycoproteomics field. He will analyze proteomic profiles of therapeutic monoclonal antibodies in the serum of patients with immune-mediated diseases and correlate them with clinical outcomes. He will try to understand why therapeutic monoclonal antibodies are more effective in some patients than others and how we can apply this knowledge to improve current treatments.

Left to right: Karli Reiding, Vojtech Franc, and Albert J.R. Heck

Meet the team @ Cambridge

Left to right: Kathryn Elsegood, Paul Lyons, Kelvin Hunter, Ken Smith, Eoin McKinney and Federica Mescia

We think that this newsletter is a good opportunity to get to know a bit better the RELENT partners. In this issue we will introduce the team in Cambridge, UK.
The University of Cambridge is one of the oldest universities and leading academic centres world-wide. The Cambridge RELENT team is lead by Ken Smith, Professor of Medicine and Head of the Department of Medicine, and Dr Paul Lyons, Principal Research Associate in the Department of Medicine. Other key people involved in RELENT are Dr Eoin McKinney, nephrologist and Wellcome Trust Clinical Fellow, Dr Federica Mescia, Clinical Research Associate, bioinformatician Kelvin Hunter and Laboratory Manager Kathryn Elsegood.
The main focus of the Cambridge team is on understanding autoimmune disease and applying this knowledge to the clinical setting, with the ultimate goal of improving the treatment of patients. Over the last decade they have set up a successful translational programme in immune and inflammatory diseases, particularly vasculitis, systemic lupus erythematosus and inflammatory bowel disease. One of their main strengths is the multidisciplinary approach that combines well-characterized patient cohorts, high-throughput genomic technologies, state-of-the-art bioinformatic methodology and experimental in vitro/animal models. This has already led to the discovery of a novel biomarker that predicts disease outcome, which is now entering clinical trials in inflammatory bowel disease, and the identification of important genes involved in disease development and progression.
The Cambridge team are collaborating with the other RELENT partners to identify genes and biomarkers that predict clinical outcome in immune-mediated disease. These efforts will provide key insights into the biological mechanisms that drive immune and inflammatory diseases, and pave the way to develop innovative therapeutics and biomarkers to be translated into the clinic. The overarching aim is to fulfill the promises of personalized medicine, finding the right treatment strategy for the right patients.

Publications

2017 has been a prolific year for the RELENT investigators, with 12 papers published in high-profile peer-reviewed scientific journals. These publications report important contributions made by the RELENT team to gain a better understanding of the pathogenesis of autoimmune diseases and identify promising novel therapeutic targets. For a complete and updated list of publications, have a look at our website.
To give you a flavor of the novel research carried out by RELENT partners, we have highlighted a couple of papers below.

Refined insights into immune mechanisms relevant to disease

The Medizinische Universität Wien team, led by Prof. Renate Kain, previously demonstrated that circulating autoantibodies directed against LAMP-2 (lysosome-associated membrane protein 2) can be detected in more than 90% of patients with active pauci-immune focal necrotizing glomerulonephritis. This is one of the most severe inflammatory diseases of the kidneys that, if untreated, can rapidly lead to kidney failure necessitating dialysis or transplant. The Wien team have gone on to further study the underlying mechanisms and discovered that LAMP-2 is involved in antigen processing pathways that affect the initiation of immune responses. These novel findings, published in the Journal of Immunology, are relevant to improve our understanding of the immune response in general and of diseases in which autoantibodies to LAMP-2 have been implicated.

Unravelling links between kidney failure and cardiovascular diseases

Kidney failure is associated with chronic inflammation and with a striking increase in the risk of cardiovascular diseases, like heart attacks and strokes, by poorly understood mechanisms. Prof. Hans-Joachim Anders, RELENT partner at Ludwig-Maximilians-Universität München, led an international collaboration to shed light on this conundrum. By studying mice and analysing the blood of more than 1900 people, they showed that levels of cathepsin-S increase in parallel with reduced kidney function. Cathepsin-S is a protein released by activated immune cells that has already been implicated in the pathogenesis of cardiovascular disease. This study, published in Scientific Reports, suggests that cathepsin-S might be a novel therapeutic target to prevent cardiovascular disease in the setting of poor kidney function.

RELENT website and Social Media

Since its release online on 29.06.2016, the RELENT website (www.relent.eu) counts 2.796 sessions by 1.925 users in 79 countries; in 27 of those countries all over the world we have even had 10 or more sessions per country. The average session duration was about 3 min on www.relent.eu. A duration of 3 minutes gives users ample time to read the content and interact with our website.

We continuously strive to attract more visitors to our website and aim to increase its visibility by linking to project partner sites, asking our own partners to refer to our website from their institutional site, linking to relevant patient organizations etc.

Visitors can find further information about the project, chronic autoimmune diseases, the partners and regular news about RELENT. Please pay us a visit and feel free to link your website to www.relent.eu!

The RELENT project is also on undefinedTwitter, undefinedLinkedIn and undefinedResearchGate. RELENT news will be posted regularly.
Please visit, connect with us and follow us – we would love to add you to our network!

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 3rd RELENT General Assembly and 5th Steering Committee Meeting will take us to the beautiful city of Groningen, The Netherlands from 24th to 26th of January 2018.

 

 
 
RELENT has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 668036. The views expressed here are the responsibility of the authors only. The EU Commission takes no responsibility for any use made of the information set out. Copyright | Imprint
 

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