ATRACTion: to change the situation in primary immunodeficiencies with autoimmunity or inflammation

The ATRACTion project, led by Frédéric Rieux-Laucat, at Imagine Institute, is one of 15 winners of the fourth call for projects “University Hospital research in health” of the French Investments for the Future program aiming to support innovative and large-scale research projects in the field of health.
Frédéric Rieux-Laucat explains this project, which aims to reduce misdiagnosis and improve the prognosis of these diseases in order to change the lives of patients by identifying the most suitable treatments.

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What is a primary immunodeficiency?

Frédéric Rieux-Laucat: The immune system is there to protect our body against environmental pathogens and to control the emergence of tumor cells, but it must also self-regulate to prevent the occurrence of autoimmune or autoinflammatory diseases. This system can fail because of a genetic defect. This is known as a primary immunodeficiency. It can result in repeated or severe infections, an increased susceptibility to some cancers, and in at least a quarter of patients it can result in autoimmune or autoinflammatory manifestations. These manifestations can sometimes be life-threatening or damage certain organs. To date, more than 350 different primary immunodeficiencies have been found. These diseases affect about one child in 5,000, i.e. several hundred births each year and several thousand people live with such a disease in France.


What are the main challenges?

FRL : Primary immunodeficiencies most often appear from birth or infancy but they can sometimes clinically present themselves in adulthood. The very diverse and more or less severe symptoms can lead to significant misdiagnosis and treatment. Most often, they require life-long treatment. In forms associated with inflammations or autoimmune diseases, these are immunosuppressants or immunotherapies, i.e. heavy treatments with significant side effects and for which the efficacy reduces over time. To date, it is not known how to distinguish between the different types of primary immunodeficiencies, or anticipate their development and the potential risks. Our goal is therefore to use innovative technologies, which rely on cell by cell analyses coupled with artificial intelligence, to better diagnose these diseases, and in particular stratify them according to the risks, to develop kits to refine the prognosis, to suggest an application to support health professionals in their diagnostic and therapeutic decisions and to develop new therapeutic strategies.


In concrete terms, how will you proceed to change the situation for these diseases?

FRL : Thanks to the Necker-Enfants Malades hospital, we already have a unique database on these diseases. It is an invaluable source of information that we intend to explore thanks to very specialized and innovative technologies: single cell analyses coupled with artificial intelligence.

If the starting point of these diseases is a genetic alteration, the biological consequences vary from one disease to another, even from one cell to another. These variations can be the consequence of gene regulation, known as epigenetics, and the microbial environment (microbiota) of each person. The strength and originality of this project is firstly to carry out analyses on the level of the single cell, which will emerge from new interaction networks or deregulated mechanisms that have not been suspected up to now in these diseases, and secondly to analyze in parallel the composition of the microbiota and the metabolites that it produces. These multiple studies and the analysis of this big data by artificial intelligence are possible due to the consortium of this project, which brings together 11 partners, academic (INSERM, APHP, INRA, CEA, University of Paris) or industrial (Sanofi and Ariana Pharma). This project therefore paves the way for a much more personalized medicine and new therapeutic solutions relying on new molecules or repositioning molecules already used in other diseases.