The role of innate immunity in disease initiation and damage control in anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.

Anti-neutrophil cytoplasmic antibody (ANCA)-mediated vasculitis (AAV) with its most prevalent manifestation, pauci-immune necrotizing crescentic glomerulonephritis (ANCA GN), is a potentially life-threatening autoimmune disease. This unique disease is characterized by antibodies directly affecting the activity and behavior of innate immune cells. It is a chronic condition with substantial risk of relapsing disease. The initial hyperinflammatory state is dominated by the innate immune system, but ongoing crosstalk with the adaptive immune system and the balance between damage and repair are crucial during the course of disease. Although we recognize the importance of the adaptive immune system in the pathogenesis of AAV, in this narrative review we provide an overview of the leading role of neutrophils and macrophages and their interplay with other components of the innate immune system in the pathogenesis of AAV and ANCA GN. Their central involvement is substantiated by increasing numbers of in vitro, in vivo, clinicopathological, molecular, and genetic studies. Classical evidence that neutrophil degranulation and reactive oxygen species play a role in ANCA GN is being expanded by recent insights into the damaging and communicative effects of neutrophil extracellular traps in ANCA GN. Macrophages, one of the most prevalent inflammatory cell types at the site of early ANCA GN, differentially contribute to inflammation, resolution, and chronicity in ANCA GN. In this narrative review, we discuss the current knowledge pertaining to the role of the innate immune system in the development and progression of ANCA GN.