• C David and M-L Frémond.
• Université de Paris, Institut Imagine, laboratoire de neurogénétique et neuroinflammation, 24, boulevard du Montparnasse, 75015 Paris, France.
• Rev Med Interne. 2022 Jun 1; 43 (6): 347-355.

AbstractType I interferonopathies (IP1) are a heterogeneous group of Mendelian diseases characterized by overactivation of the type I interferon (IFN) pathway. They are caused by monogenic (rarely digenic) mutations of proteins involved in this key pathway of innate immunity. IP1 transmission can be dominant, recessive or X-linked and penetrance differs from one IP1 to another. The clinical spectrum is broad and mainly includes central nervous system involvement with calcifications of the basal ganglia, skin disorders such as cutaneous vasculitis that can be mutilating. Joint disorders including non-destructive deforming arthropathy, pulmonary involvement such as intra-alveolar haemorrhage or interstitial lung disease, and haematological symptoms with cytopenia and/or immune deficiency are also seen. The clinical manifestations vary from one IP1 to another and their spectrum is constantly expanding along with the description of new IP1s and patients. The inflammatory syndrome is generally mild and autoimmune stigmata are frequently found. Almost all patients display overexpression of the type I IFN pathway detected, for instance, by the evaluation of IFN-stimulated genes expression, referred as "interferon signature". The related morbidity and mortality are high. However, the beneficial effect on certain symptoms of targeted therapies inhibiting type I IFN, such as JAK inhibitors, has led to a promising improvement in the management of these patients.Copyright © 2021 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

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