Objective
Membranous nephropathy (MN) is a paradigm of organ-specific autoimmune disease which affects the kidney glomerulus, resulting in the formation of immune deposits, complement-mediated proteinuria, and renal failure. My group has recently identified 2 causative antigens (neutral endopeptidase and bovine serum albumin) in children, and 2 predisposing genes HLA-DQA1 and PLA2R1 coding for another antigen in adult MN. However, MN is most likely more complex, involving several antigen-antibody systems and immune response genes. To get a comprehensive view of self and food/environmental antigenic targets and of HLA and non-HLA trigger genes, and to design new rapidly acting therapies, I will develop novel technological approaches such as immunopeptidomics, and explore new pathophysiological and therapeutic concepts with 3 major objectives:
1. Identify the immune response targets (epitopes) using unbiased approaches such as HLA-class II peptidomics, random peptide libraries, and sequencing of candidate genes starting with PLA2R1
2. Investigate trigger genes by next generation sequencing (NGS) of the HLA-D locus and of other genes involved in autoimmunity and disease progression, in 150 pairs of donors and recipients with or without recurrence of MN, a situation offering a unique opportunity to analyze effects of genetic background
3. Revisit complement-related innate immunity by NGS sequencing of 18 complement regulatory protein genes in search of variants which may account for disease heterogeneity, by blocking C5b-9 formation with recombinant factor H in 2 murine models of MN, and by searching for C5b-9 antagonists by high-throughput screening of chemical libraries in podocyte cell-based assays.
Our project will provide new biomarkers that will be used to set up reliable tests for diagnosis, monitoring, and prediction of outcome and recurrence of MN. It will result in new therapies, improved monitoring and ontology, and better understanding of organ-specific autoimmunity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences computer and information sciences knowledge engineering ontology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology autoimmune diseases
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-ADG_20120314
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.