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AUTOCOMPLEMENT SIGNED

The role of complement in the induction of autoimmunity against post-translationally modified proteins

Total Cost €

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EC-Contrib. €

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Partnership

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 AUTOCOMPLEMENT project word cloud

Explore the words cloud of the AUTOCOMPLEMENT project. It provides you a very rough idea of what is the project "AUTOCOMPLEMENT" about.

reactive    pathogens    mediated    rheumatoid    ptm    unravel    absence    property    lupus    vaccine    carbamylation    function    autoimmune    autoreactivity    direct    hypothesise    post    therapies    auto    questions    translationally    antibodies    potentiate    erythematosus    systemic    prevalent    utilize    autoadjuvant    immunity    adaptive    modifications    breach    physiological    biomarkers    influenced    bind    diagnostic    ra    elucidate    autocomplement    despite    either    diseases    killing    prognostic    efficacy    proteins    protein    strategies    inhibit    immune    positive    block    exogenous    anti    antibody    modified    plan    tolerance    interaction    cell    data    patient    cells    receive    complement    vaccination    binding    suggests    induce    associations    answering    adjuvant    care    examples    preliminary    autoimmunity    pathogenic    unknown    boost    signals    arthritis    formed    autoantibodies    reveal    immunization    wealth    clinical    sle    tools    decrease    citrullination    playing   

Project "AUTOCOMPLEMENT" data sheet

The following table provides information about the project.

Coordinator
ACADEMISCH ZIEKENHUIS LEIDEN 

Organization address
address: ALBINUSDREEF 2
city: LEIDEN
postcode: 2333 ZA
website: www.lumc.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 1˙999˙802 €
 EC max contribution 1˙999˙802 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACADEMISCH ZIEKENHUIS LEIDEN NL (LEIDEN) coordinator 1˙999˙802.00

Map

 Project objective

In many prevalent autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) autoantibodies are used as diagnostic and prognostic tools. Several of these autoantibodies target proteins that have been post-translationally modified (PTM). Examples of such modifications are citrullination and carbamylation. The success of B cell-targeted therapies in many auto-antibody positive diseases suggests that B cell mediated auto-immunity is playing a direct pathogenic role. Despite the wealth of information on the clinical associations of these anti-PTM protein antibodies as biomarkers we have currently no insight into why these antibodies are formed. Immunization studies reveal that PTM proteins can induce antibody responses even in the absence of exogenous adjuvant. The reason why these PTM proteins have ‘autoadjuvant’ properties that lead to a breach of tolerance is currently unknown. In this proposal, I hypothesise that the breach of tolerance towards PTM proteins is mediated by complement factors that bind directly to these PTM. Our preliminary data indeed reveal that several complement factors bind specifically to PTM proteins. Complement could be involved in the autoadjuvant property of PTM proteins as next to killing pathogens complement can also boost adaptive immune responses. I plan to unravel the importance of the complement–PTM protein interaction by answering these questions: 1) What is the physiological function of complement binding to PTM proteins? 2) Is the breach of tolerance towards PTM proteins influenced by complement? 3) Can the adjuvant function of PTM be used to increase vaccine efficacy and/or decrease autoreactivity? With AUTOCOMPLEMENT I will elucidate how PTM-reactive B cells receive ‘autoadjuvant’ signals. This insight will impact on patient care as we can now design strategies to either block unwanted ‘autoadjuvant’ signals to inhibit autoimmunity or to utilize ‘autoadjuvant’ signals to potentiate vaccination.

 Publications

year authors and title journal last update
List of publications.
2019 Douwe J. Dijkstra, Jivan V. Joeloemsingh, Ingeborg M. Bajema, Leendert A. Trouw
Complement activation and regulation in rheumatic disease
published pages: 101339, ISSN: 1044-5323, DOI: 10.1016/j.smim.2019.101339
Seminars in Immunology 45 2020-04-24
2020 R. Lubbers, S. C. Oostindie, D. J. Dijkstra, P. W. H. I. Parren, M. K. Verheul, L. Abendstein, T. H. Sharp, A. Ru, G. M. C. Janssen, P. A. Veelen, E. T. J. den Bremer, B. Bleijlevens, B.‐J. Kreuk, F. J. Beurskens, L. A. Trouw
Carbamylation reduces the capacity of IgG for hexamerization and complement activation
published pages: 1-11, ISSN: 0009-9104, DOI: 10.1111/cei.13411
Clinical & Experimental Immunology 200/1 2020-04-15
2019 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
Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
published pages: 908-916, ISSN: 0003-4967, DOI: 10.1136/annrheumdis-2018-214950
Annals of the Rheumatic Diseases 78/7 2020-04-15
2020 Maaike Biewenga, Arantza Farina Sarasqueta, Maarten E. Tushuizen, Eveline S.M. de Jonge-Muller, Bart van Hoek, Leendert A. Trouw
The role of complement activation in autoimmune liver disease
published pages: 102534, ISSN: 1568-9972, DOI: 10.1016/j.autrev.2020.102534
Autoimmunity Reviews 2020-04-15

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