The role of monocytes in ANCA-associated vasculitides

Abstract

The anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are a heterogeneous group of diseases causing inflammation in small blood vessels and linked by the presence of circulating ANCA specific for proteinase 3 (PR3) or myeloperoxidase (MPO). These antigens are present both in the cytoplasmic granules and on the surface of neutrophils, and the effect of ANCA on neutrophil biology has been extensively studied. In contrast, less attention has been paid to the role of monocytes in AAV. These cells contain PR3 and MPO in lysosomes and can also express them at the cell surface. Monocytes respond to ANCA by producing pro-inflammatory and chemotactic cytokines, reactive-oxygen-species and by up-regulating CD14. Moreover, soluble and cell surface markers of monocyte activation are raised in AAV patients, suggesting an activated phenotype that may persist even during disease remission. The presence of monocyte-derived macrophages and giant cells within damaged renal and vascular tissue in AAV also attests to their role in pathogenesis. In particular, their presence in the tertiary lymphoid organ-like granulomas of AAV patients may generate an environment predisposed to maintaining autoimmunity. Here we discuss the evidence for a pathogenic role of monocytes in AAV, their role in granuloma formation and tissue damage, and their potential to both direct and maintain autoimmunity. ANCA-activation of monocytes may therefore provide an explanation for the relapsing-remitting course of disease and its links with infections. Monocytes may thus represent a promising target for the treatment of this group of life-threatening diseases.

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“…Inflammation has been suggested to be the underlying pathogenesis of a range of the most common cardiovascular diseases [23,24]. Myeloblastin is a protease that degrades proteins such as elastin, fibronectin, laminin and collagen and has mainly been investigated in vasculitis [25]. Azurocidin, also known as cationic antimicrobial protein CAP37 or heparin-binding protein is an important multifunctional inflammatory mediator [26].…”

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Biomarkers in Renal Vasculitis

“…Furthermore, monocyte-derived macrophages and giant cells within affected tissues and granulomas may be responsible for maintaining autoimmunity. These data suggest that monocytes may account for disease relapse, thus be used as a prognostic biomarker of negative outcome [21].…”