Type I interferon (IFN) is a potent substance. As such, the induction, transmission and resolution of the type I IFN-mediated immune response are tightly regulated. The type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system due to Mendelian mutations, and their molecular definition has the potential to dissect fundamental aspects of IFN control in the human context. Of note, the recognition of type I interferonopathies is becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both IFN and non-IFN related, and that a primary disturbance of the innate immune system can ‘spill-over’ into autoimmunity in some cases. Indeed, the fact that a number of non-Mendelian disorders, particularly systemic lupus erythematosus (SLE) and dermatomyositis, are also characterized by an upregulation of type I IFN signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.

Learning Objectives

• Describe the phenotypic breadth of the type I interferonopathies

• Describe the molecular basis of the type I interferonopathies

• Describe the status of interferon signalling in the type I interferonopathies

• Describe the clinical link between the type I interferonopathies and SLE

• Describe the link between the molecular pathology of the type I interferonopathies and SLE