Isabelle Melki1,2,3,4, Marie-Louise Frémond5. 1. Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France. isabelle.melki@aphp.fr. 2. General Paediatrics, Infectious Disease and Internal Medicine Department, Hôpital Robert Debré, AP-HP, Paris, France. isabelle.melki@aphp.fr. 3. Paediatric Haematology-Immunology and Rheumatology Department, Hôpital Necker-Enfants Malades, AP-HP, Paris, France. isabelle.melki@aphp.fr. 4. Reference centre for Rheumatic, AutoImmune and Systemic diseases in childrEn (RAISE), Paris, France. isabelle.melki@aphp.fr. 5. Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, Paris, France.
Abstract
PURPOSE OF THE REVIEW: Type I interferonopathies are monogenic autoinflammatory diseases induced by constitutive activation of type I interferon. Here, we provide an overview of these diseases and describe underlying molecular pathways, related phenotypes, suggestive clinical signs and investigations for helping diagnosis process and therapeutic management. RECENT FINDINGS: Recent genetic and functional discoveries have enabled deciphering mechanisms involved in the pathogenesis of the type I interferonopathies and considering promising targeted treatments, such as JAK inhibitors, both for monogenic and multifactorial interferon-related diseases. The concept of the type I interferonopathies rests on the assumption that some diseases arise from a disturbance of interferon signalling pathway. In the presence of suggestive clinical signs (especially involving the central nervous system and the skin), a consistent positive type I interferon assessment is a further point in favour of genetic investigations in patients. This review also highlights the potential value of targeted therapeutics that should improve features of type I interferonopathies, thereby providing a validation of the underlying hypothesis.
PURPOSE OF THE REVIEW: Type I interferonopathies are monogenic autoinflammatory diseases induced by constitutive activation of type I interferon. Here, we provide an overview of these diseases and describe underlying molecular pathways, related phenotypes, suggestive clinical signs and investigations for helping diagnosis process and therapeutic management. RECENT FINDINGS: Recent genetic and functional discoveries have enabled deciphering mechanisms involved in the pathogenesis of the type I interferonopathies and considering promising targeted treatments, such as JAK inhibitors, both for monogenic and multifactorial interferon-related diseases. The concept of the type I interferonopathies rests on the assumption that some diseases arise from a disturbance of interferon signalling pathway. In the presence of suggestive clinical signs (especially involving the central nervous system and the skin), a consistent positive type I interferon assessment is a further point in favour of genetic investigations in patients. This review also highlights the potential value of targeted therapeutics that should improve features of type I interferonopathies, thereby providing a validation of the underlying hypothesis.
Entities:
Keywords:
Autoimmunity; Autoinflammation; JAK inhibitors; Reverse-transcriptase inhibitors; Type I interferon; Type I interferonopathies
Authors: Mirjam A Beck; Heinz Fischer; Lisa M Grabner; Tamara Groffics; Mircea Winter; Simone Tangermann; Tina Meischel; Barbara Zaussinger-Haas; Patrick Wagner; Carina Fischer; Christina Folie; Julia Arand; Christian Schöfer; Bernard Ramsahoye; Sabine Lagger; Georg Machat; Gregor Eisenwort; Stephanie Schneider; Alexandra Podhornik; Michael Kothmayer; Ursula Reichart; Martin Glösmann; Ido Tamir; Michael Mildner; Raheleh Sheibani-Tezerji; Lukas Kenner; Peter Petzelbauer; Gerda Egger; Maria Sibilia; Andrea Ablasser; Christian Seiser Journal: EMBO J Date: 2021-09-29 Impact factor: 11.598