Proof-of-concept study - Systemic autoinflammatory diseases

Systemic autoinflammatory diseases (SAIDs) are a set of rare heterogeneous conditions characterized by periodic or chronic systemic inflammation caused by the abnormal activation of the innate immunity in the absence of infection or autoimmunity.

Due to the genetic nature of these disorders, most of SAIDs patients developed symptoms early on their life [1,2]. Approximately 60 genes involving different parts of the innate immune system have been identified, as well as a wide spectrum of clinical manifestations. Therefore, diagnosis relies mainly on genetic testing and suspicion, resulting in a delay of 7.3 years as disease-causing mutations cannot be identified for 40-60% of patients [3]. This highlights the need for the identification of objective diagnostic markers and the description of the pathophysiology of SAIDs to avoid delay and inadequate treatments.

Here, we’re planning to use our platform for single-cell measurement to assess cellular dysregulation and activation of innate immune cells and identify involved disease pathways. The aim of this project is to improve and accelerate the diagnosis of SAIDs through the identification of molecular signatures and signaling pathways and contribute further to a better management of symptoms, by the identification of the most appropriate treatment for each disease and patient.

This project is a close collaboration with Dr. Irina Giurgea (Sorbonne University, Laboratory of childhood genetic diseases, INSERM UMR_S933, Paris), an internationally recognized expert in the molecular and cellular biology of SAIDs.

[1] Georgin-Lavialle S, Ducharme-Benard S, Sarrabay G, Savey L, Grateau G, Hentgen V. Systemic autoinflammatory diseases: Clinical state of the art. Best Pract Res Clin Rheumatol. 2020 Aug;34(4):101529. doi: 10.1016/j.berh.2020.101529. Epub 2020 Jun 13.  

[2] Krainer J, Siebenhandl S, Weinhäusel A. Systemic autoinflammatory diseases. J Autoimmun. 2020 May;109:102421. doi: 10.1016/j.jaut.2020.102421. Epub 2020 Feb 1.  

[3] Toplak N, Frenkel J, Ozen S, et al An International registry on Autoinflammatory diseases: the Eurofever experience. Annals of the Rheumatic Diseases 2012;71:1177-1182.