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Content archived on 2024-05-29

Marie-Curie grant on primary Immuno-deficiencies and Auto-Immune diseases

Objective

Primary immunodeficiency diseases are rare congenital conditions. They represent an experiment of nature, demonstrating the importance of specific genes and proteins in the host defence against pathogens. In primary immuno deficiencies the susceptibility to infections often goes along with the development of autoimmune conditions. In the most prevalent human primary immunodeficiency requiring medical attention, termed Common Variable ImmunoDeficiency (CVID), the prevalence of autoimmunity is approximately 25%. Mutations in the TNF-like B cell receptor TACI, which is expressed in the germinal centre in secondary lymphoid organs, account for up to 10% of the CVID cases.

In TACI deficiency, lymphoproliferation is observed in 2/3 of the patients and autoimmune conditions in approximately 1/3 of the patients. The ligand of TACI, termed BAFF, has been shown to take a centre stage in common human autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In addition to TACI, BAFF binds also to BCMA and BAFF receptor. Which of these receptors however, contribute to the development of autoimmunity has not yet been studied.

This Marie-Curie application now would like to extend the applicant's findings in TACI deficiency in CVID to other disease entities and would like to address the role of TACI in autoimmunity and ultimately address the hypothesis that some patients with an antibody deficiency syndrome may in fact suffer from an autoimmune condition in which the antibody producing cells ar e the target of autoimmunity.

This hypothesis is supported by following observations:
1. TACI-knockout mice suffer from an SLE-like autoimmune condition
2. Lymphoproliferation is observed in two thirds of patients with TACI and one third have an overt autoimmune disease
3. Autoimmune diseases are common in patients with CVID (approx. 25%) 4. B cell numbers in CVID patients are low (<6% of PBMCs) in 25% of the cases, and tend to decrease over time

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Call for proposal

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FP6-2005-MOBILITY-8
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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

UNIVERSITY COLLEGE LONDON
EU contribution
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Total cost

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