Type I Interferons in Systemic Autoimmune Diseases: Distinguishing Between Afferent and Efferent Functions for Precision Medicine and Individualized Treatment

A sustained increase in type I interferon (IFN-I) may accompany clinical manifestations and disease activity in systemic autoimmune diseases (SADs). Despite the very frequent presence of IFN-I in SADs, clinical manifestations are extremely varied between and within SADs. The present short review will address the following key questions associated with high IFN-I in SADs in the perspective of precision medicine. 1) What are the mechanisms leading to high IFN-I? 2) What are the predisposing conditions favoring high IFN-I production? 3) What is the role of IFN-I in the development of distinct clinical manifestations within SADs? 4) Would therapeutic strategies targeting IFN-I be helpful in controlling or even preventing SADs? In answering these questions, we will underlie areas of incertitude and the intertwined role of autoantibodies, immune complexes, and neutrophils.