Imaging findings in pediatric interferonopathies

Type I interferon (IFN-I) is a proinflammatory cytokine that activates signalling pathways crucial for antiviral defence in innate immunity. The IFN-I system is a self-preserving mechanism that normally responds to exogenous nucleic acids derived from pathogens, but not to endogenous nucleic acids from host cells. However, genetic defects that constitutively activate this pathway can lead to aberrant IFN-I production (the "IFN signature") and sterile inflammation (autoinflammation), giving rise to a group of monogenic disorders collectively termed "autoinflammatory interferonopathies." This emerging perspective was initially prompted by the phenotypic similarities between Aicardi-Goutières syndrome and congenital toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex (TORCH) infection. Autoinflammatory interferonopathies can manifest with variable combinations of cutaneous changes, encephalopathy, vasculopathy, interstitial lung disease, and other features (e.g., skeletal changes), and are commonly accompanied by autoimmunity. More recently, the IFN signature has also attracted attention in autoimmune diseases such as systemic lupus erythematosus and dermatomyositis, which have been increasingly referred to as "autoimmune interferonopathies." Collectively, interferonopathies provide a novel framework for immune-mediated diseases spanning an autoinflammatory-autoimmune continuum. Here, we outline the clinical, imaging, and pathogenic features of paediatric interferonopathies. While each disorder has distinctive imaging findings, many share common patterns reflecting common underlying pathophysiology.