Editorial: DADA2 and other monogenic vasculitides

Abstract

Editorial on the Research Topic DADA2 and other monogenic vasculitidesSystemic vasculitis broadly defines a heterogenous group of inflammatory diseases that primarily affect blood vessels (1). The etiology of most systemic vasculitides remains unknown and the forms of vasculitis in children and adults are not the same. Among primary vasculitides, IgA vasculitis and Kawasaki disease are common in young children, whereas some such as Takayasu arteritis and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis are more common in adults. The landmark discoveries of deficiency of adenosine deaminase 2 (DADA2) and STING-associated vasculopathy of infancy (SAVI) redefined the paradigm of systemic vasculitis (2-4). These monogenic forms of secondary vasculitis often manifest early in life and inflict devastating consequences in children and adults (5). While the causal genes for DADA2 and SAVI are defined, we have much more to learn about the complex pathophysiology of these conditions. In the Research Topic "DADA2 and other Monogenic Vasculitides," we aim to advance the pathophysiology, diagnostic evaluation, and treatment for these intriguing yet potentially fatal diseases. An overview of monogenic vasculitidesReview articles by Signa et al. and Wobma et al. provide excellent summaries of DADA2 and SAVI, respectively. Although the precise mechanism linking defective ADA2 function to the plethora of manifestations in DADA2 remains unclear, Signa et al. synthesize the abundant evidence pointing to abnormalities in both innate immunity and adaptive immunity. Aberrant monocyte polarization and neutrophil extracellular traps are potential explanations for the excess tumor necrosis factor (TNF) production (4, 6). Recent studies also suggest dysregulation of type I interferons (IFN-I) in DADA2 (7-9), although the role of these antiviral cytokines awaits further clarification. Wobma et al. review the stimulator of interferon genes (STING) axis of IFN-I production and discuss how dysregulation of this pathway leads to immune activation and progressive Frontiers in Immunology frontiersin.org 01