What is myeloperoxidase doing in ANCA-associated glomerulonephritis? William G. Couser, Richard J. Johnson  Kidney International  Volume 88, Issue 5, Pages 938-940 (November 2015) DOI: 10.1038/ki.2015.259 Copyright © 2015 International Society of Nephrology Terms and Conditions

Figure 1 Schematic depiction of the three established roles for MPO in mediating glomerular injury in AAV. Etiologic agents, primarily environmental exposures such as infections and drugs, activate the innate immune system with cytokine-induced neutrophil activation and release of extracellular MPO in free form or within neutrophil extracellular traps (NETs). MPO localizes in glomeruli on the basis of charge interactions with glomerular anionic sites. Subsequent activation of the adaptive immune response to MPO includes both antibody (ANCA) and T-cell components. Both can contribute to the final necrotizing, crescentic glomerular lesion. In addition, the glomerular bound MPO demonstrated by O’Sullivan et al1 can react in situ with H2O2 and a halide to induce halogenation of glomerular capillaries that also likely contributes to the severity of injury. Although all three of these MPO-induced responses have been well documented to induce severe glomerular injury in vivo in animal models, the relative contribution of each pathway in humans is unknown. Blue: immune responses to MPO; purple: genetic modulation of the immune response; red: direct toxicity of MPO; yellow: release of MPO from neutrophils and glomerular localization; green: components of the glomerular pathology in AAV. Kidney International 2015 88, 938-940DOI: (10.1038/ki.2015.259) Copyright © 2015 International Society of Nephrology Terms and Conditions