A GENE SIGNATURE FOR DIAGNOSING STIMULATOR OF INTERFERON GENES (STING)-ASSOCIATED VASCULOPATHY WITH ONSET IN INFANCY (SAVI)

Gain-of-function mutations in STING1, that codes for the Stimulator of Interferon Gene (STING), result in a severe autoinflammatory disease termed STING-associated vasculopathy with onset in infancy (SAVI). Although elevated type I interferon (IFN) production is thought to be the leading cause of the symptoms observed in patients, STING can induce a set of pathways, and their role in the onset and severity of SAVI remains to be elucidated. To address this point, the inventors compared a single-cell RNA sequencing (scRNA-seq) dataset of peripheral blood mononuclear cells (PBMCs) from SAVI patients to a dataset of healthy PBMCs treated with recombinant IFN-β. In particular, scRNA-seq clustering identified a patient-specific subset of monocytes, highly inflammatory and expressing a strong integrated stress response (ISR). Even more particularly, the inventors have identified at the transcriptomic level a STING-associated signature of 21 genes that is driven by STING activation, independently of type I IFN. This signature is therefore suitable to better distinguish SAVI from other type I interferonopathy.

Keywords: STING-associated vasculopathy with onset in infancy (SAVI), RNA Signature, Diagnostic, Prognosis, Treatment response prediction
Patent Application number: International Procedure (PCT) - 27 Mars 2023 - PCT/IB2023/000159
Inventors:
MENAGER Mickaël; RIEUX-LAUCAT Frédéric
Publications:
Cell Rep Med, 2023 Dec 19;4(12):101333., De Cevins et al. , Single-cell RNA-sequencing of PBMCs from SAVI patients reveals disease-associated monocytes with elevated integrated stress response, doi: 10.1016/j.xcrm.2023.101333.

Reference:

BIO23085-D1

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Patent filling date: 2023-03-27
Rare disease: Yes

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