RELENT NEWS | Issue 6 | 04/2020
 
 
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RELENT NEWS | Issue 6 | 04/2020
 
 

Welcome to the RELENT newsletter!

With this 6th issue of our bi-annual newsletters 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 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 and there are currently no ways to distinguish individuals who will have a relatively benign course from those destined to have frequent relapses – and therefore need intensive early treatment. The RELENT project is systematically applying an entirely novel approach to define disease mechanisms common to many autoimmune diseases using a strategy that involves 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. This should provide the foundation for individually customised treatment plans for those with severe 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 combine clinical, serological, genetic, and transcriptomic to 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 six months a number of events have taken place.

RELENT final General Assembly Meeting and 8th Steering committee meeting

The 6th and final General Assembly Meeting and the 8th Steering committee meeting took place in Vienna on the 4th and 5th of March.

 

This meeting offered the opportunity to provide a final update on progress made over the last few months as well as to summarize the work done in each work package. The meeting also gave young researchers the opportunity to present and discuss their data. Overall, this meeting highlighted the numerous new findings achieved by the RELENT consortium as illustrated by the substantial number of publications within highly ranked peer-review journals.
The progress of the project thus demonstrated the feasibility of an individualized treatment for each patient to prevent relapses in chronic autoimmune diseases.

RELENT International Symposium

Following the General Assembly meeting, RELENT hosted an International Symposium on the 6th of March. This symposium, which took place in Vienna and was open to the general public free of charge, provided an opportunity to present the novel findings and major achievements reached over the last 5 years by the consortium. In addition to the RELENT partners, key-note speakers were invited which promoted a lively discussion and exchange of ideas between the broad range of participants, including basic scientists, clinicians, and industry partners but also patients and students. The highlights of RELENT presented during the symposium increased our understanding of chronic auto-immune diseases and brought us closer to better and more precise treatment for patients. 

RELENT @ the American Society of Nephrology

In November 2019 at the American Society of Nephrology’s Kidney Week at the Washington convention center (USA), two of the RELENT Principal Investigators spoke at the session entitled “Leveraging T cells and Macrophages in Glomerular Diseases”: Richard Kitching, (Monash University) and Peter Heeringa (UMCG Groningen). This session discussed the recent progress in the understanding of macrophage and T cells biology together with their contribution to autoimmune and glomerular disease as well as their potential as new therapeutic approaches. The talk of Professor Kitching focused on chimeric antigen receptor (CAR) T cells in Glomerulonephritis whilst Professor Heeringa discussed the disease flares in ANCA-associated GN: Urine Analysis of Macrophage Activation.

The University of Melbourne has made Christian Kurts an Honorary Professor

Professor Christian Kurts, co-leader of Work Package 4 and the Principal Investigator of the RELENT team at the University of Bonn has been appointed an Honorary Professor at the University of Melbourne. Professor of Experimental Immunology, Professor Kurts received his immunology training at the University of Melbourne and together with his Australian colleague Sammy Bedoui founded the Bonn & Melbourne Research and Graduate School of Immunology. This project is funded by the German Research Foundation and allows students to join the International Graduate College and receive training in two universities, one in Bonn (Germany) and another one in Melbourne (Australia).  Students enrolled in this program spend 2 years at home and one year abroad. Projects focus on the role of myeloid antigen-presenting cells in tumors, autoimmune disorders, infection, and vaccination.

Besides this prestigious award, Christian Kurts also took part in numerous conferences as invited chair (German Society of Nephrology meeting – Dusseldorf 2019) as well as invited speaker (9th International Conference on Autoimmunity - Greece 2019, 3rd Australasian-German Immunology meeting – Australia 2019, Arbeitskreis Dendritische Zellen der DGfl – Germany 2019).

RELENT partner’s Hans-Joachim Anders among the authors of the new primer on lupus nephritis

A Nature Reviews Disease Primer on lupus nephritis was recently published with Hans-Joachim Anders, RELENT partner from the Ludwig-Maximilians-University Munich – LMU. These State-of-the-Art reviews cover all aspects of a specific disease and are divided into modules including epidemiology, pathophysiology, diagnosis, screening, and prevention, together with management, quality of life and prognosis. The authors provide a global overview of the field of lupus nephritis. These prestigious Disease Primer reviews are written by panels of internationally acknowledged scientists, clinical investigators and translational researchers.

Congratulation to Rebeca Hid Cadena for her PhD defense

On the 27th of January 2020, Rebeca Hid successfully defended her PhD thesis entitled “Immune checkpoint pathways in the ageing immune system and their relation to vasculitides” at the University of   Groningen. She was supervised by Peter Heeringa and Elisabeth Brouwer, and her work used samples from cohorts of healthy elderly individuals and those with vasculitis to define age-dependent alterations of proteins expressed on the surface in circulating leukocyte subsets. Her work provided the first demonstration of the influence of age and sex on the expression of immune checkpoint molecules and identified a crucial role for the immune checkpoint VISTA in the pathology of large-vessels vasculitis. Her work was an essential part of the Groningen contribution to the RELENT program.

Welcome to new members of the RELENT team

Shaghayegh Bayati

Shaghayegh Bayati joined the RELENT team at KTH in July 2019. Shaghayegh is from Iran where she performed her bachelor's degree and was followed by a Master's degree in Molecular Biology of Cells at the University of Milan (Italy). During her master thesis, she studied the formation of the protein complex CHCHD4 and the Apoptosis-Inducing Factor as well as methods to optimize its purification. Following her graduation in July 2019, she moved to Sweden to work on validation of RELENT autoantibody profiling, specifically on the reactivity of Kinesines in vasculitis, Systemic lupus erythematosus and healthy controls. She was appointed to a post as an Early-Stage Researcher (ESR13) within the HELICAL MSC Innovative Training Network (undefinedhttp://helical-itn.eu/) in December to investigate the spatial relationship of autoantibody profiles during vasculitis flares. This work originated from the results of RELENT research and thus provides and sustains its legacy.



Zohra Oubari

Zohra Oubari has recently joined the RELENT team as a short-term research fellow. Zohra is a final year Clinical Research Associate trainee in Paris and is currently carrying out an internship under the supervision of Prof Benjamin Terrier, vice-president of the French Vasculitis Study Group.
Thanks to the RELENT fellowship, Zohra is now working in close collaboration with the Cambridge RELENT team, contributing to an international genome-wide association study in ANCA-associated vasculitis (AAV). Zohra is collecting clinical data for over 200 AAV patients that the French Vasculitis Study Group has contributed to the project. Her work, together with that of the many collaborators from the European Vasculitis Genetic Consortium, will be key to study how genetic variation can affect patients’ prognosis in this severe immune-mediated disease.





Meet the team @ Medical University of Vienna, Austria

With over 650 years of experience, the Medical University of Vienna (MedUni Wien) is now embedded into the General Hospital of Vienna, which is one of the largest hospitals in Europe. This provides an excellent foundation for interdisciplinary endeavours both in basic and especially translational research. Mainly involved in WP1 the MedUni Wien team members focus their work on finding and analysing the influence of genomic pathways, as well as on the role of autophagy, on the intensity and persistence of autoimmune and inflammatory diseases. To aid this we also work on a patient-derived induced pluripotent stem cell (iPSC)-based cellular model that provides a highly effective system for analysing cell biological processes in patient derived iPSC that have been differentiated into monocytes, macrophages, and monocyte-derived dendritic cells. These cells have the genetic background of the patients from whom they originated and provide a unique opportunity to analyse genetically determined differences in inflammatory cell function.


Professor Renate Kain, head of the Department of Pathology at the MedUni Wien leads the Renal Pathology and Immunology Group and also acts as RELENT project coordinator and WP1 leader. Other researchers involved in the RELENT project are Virginie Hubert, post-doc, Stefan Schulz, a 3rd year PhD student, Emerson Collazo, a medical doctor and 4th year PhD student. Gertrude Krainz, the Professor Kain’s Personal Assistant has essential roles in the management and administration of RELENT. The MedUni Wien research team’s contribution to the RELENT program includes:

  • The established and standardized protocols to differentiate induced pluripotent stem cells (iPSC) into monocyte, macrophages and dendritic cells
  • The development of iPSC based cellular models for studying chloroquine-induced phospholipidosis
  • The identification of genetic mutation or single nucleotide polymorphism associated with the development of drug-induced phospholipidosis
  • The characterisation of the influence of FOXO3 polymorphysms in autophagy, and determining whether genetic differences in autophagy influence patient outcome in vasculitis.

 

In other projects, the Renal Pathology and Immunology Group is characterising exosomes purified from individuals with severe inflammatory disease to determine their potential as biomarkers. This, and a second project, entitled “Computer-assisted morphometry of pathological changes in renal biopsies from patients with AAV”, are performed part of HELICAL, an MSC Innovative Training Network (undefinedhttp://helical-itn.eu/). Furthermore, the MedUni Wien team is investigating the role of the matrix glycoprotein, Tenascin-C, in acute injury and subsequent scarring in ANCA-associated vasculitis.

 

Publications

The following papers have been published within the last months. These publications increased our understanding of the pathogenesis of autoimmune disorders and bring us closer to the identification and development of novel therapeutic targets.

1.    Jobin K, Stumpf NE, Schwab S, Eichler M, Neubert P, Rauh M, Adamowski M, Babyak O, Hinze D, Sivalingam S, Weisheit C, Hochheiser K, Schmidt S, Meissner M, Garbi N, Abdullah Z, Wenzel U, Hölzel M, Jantsch J, Kurts C. 2020. A high-salt diet compromises the neutrophil response against bacterial infections through hormonal perturbations. Science Translat Med, in press

2.    Enders M*, Franken L*, Philipp MS*, Kessler N*, Baumgart AK, Eichler M, Wirtz E, Garbi N*, Kurts C*. 2020. Splenic red pulp macrophages cross-prime early effector CTL that provide rapid defense against viral infections. J Immunol, Jan 1;204(1):87-100

3.    Rehm SRT, Smirnova NF, Morrone C, Götzfried J, Feuchtinger A, Pedersen J, Korkmaz B, Yildirim AÖ, Jenne DE.2019. Premedication with a cathepsin C inhibitor alleviates early primary graft dysfunction in mouse recipients after lung transplantation. Sci. Rep. 9;9(1):9925

4.    Marti Fernandez I, Macrini C, Krumbholz M, Hensbergen PJ, Hipgrave Ederveen AL, Winklmeier S, Vural A, Kurne A, Jenne D, Kamp F, Gerdes LA, Hohlfeld R, Wuhrer M, Kümpfel T, Meinl E. 2019. The Glycosylation Site of Myelin Oligodendrocyte Glycoprotein Affects Autoantibody Recognition in a Large Proportion of Patients. Front. Immunol. 10:1189

5.    Reiding KR, Franc V, Huitema MG, Brouwer E, Heeringa P, Heck AJR. Neutrophil myeloperoxidase harbors distinct site-specific peculiarities in its glycosylation. J Biol Chem. 2019;294(52):20233–20245. undefineddoi:10.1074/jbc.RA119.011098

6.    Shochet L, Holdsworth SR, Kitching AR. Animal Models of ANCA Associated Vasculitis Front. Immunol., 2020, 11: undefinedhttps://doi.org/10.3389/fimmu.2020.00525

A complete and updated list of publications is available on the RELENT website:
undefinedhttps://www.relent.eu/news/publications/

RELENT website and Social Media

The RELENT website went online on 29th of June 2016 and there you 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 Twitter with 186 followers, on LinkedIn with 87 followers and on ResearchGate with 46 followers and 743 reads. 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

RELENT will be represented at the Autoimmunity 2020 Conference in Athens by the group of Peter Nilsson (KTH, partner 7) who got an abstract accepted for oral presentation. Professor Richard Kitching (Monash, partner 9) will represent RELENT at the American Society of Nephrology’s Kidney Week (October 2020), speaking on restoring tolerance to the proteins (autoantigens) that cause ANCA-associated vasculitis.

 
 
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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