Macrophage immunity in ANCA-associated vasculitis

This thesis examines the pathophysiology of the systemic autoimmune disease ANCA-associated vasculitis (AAV), focusing on both acute and long-term effects. Part I explores the role of macrophages in renal inflammation. Despite being the primary infiltrating immune cells in early glomerular lesions, their exact functions have long remained unknown. Chapter 2 reviews the role of monocytes and macrophages in AAV pathophysiology. Chapter 3 presents a single-cell RNA sequencing study using kidney biopsies from AAV patients and controls, revealing increased proportions of CD163⁺ macrophages, primarily classical monocyte-derived macrophages expressing specific pro-inflammatory mediators, alongside a distinctive SPP1⁺ macrophage subset linked to lipid metabolism and fibrosis.
Part II delves into the pathophysiology and risk factors for cardiovascular disease. Chapter 4 reveals alterations in monocyte phenotype during active disease, while intrinsic adhesion and migration capacities remain unchanged. This chapter also delineates differences between the PR3-AAV and MPO-AAV subtypes. Chapter 5 identified risk factors for cardiovascular events in AAV, such as age, HbA1c levels, the presence of diabetes mellitus, and cardiovascular history.
Part III emphasizes the high risk of AAV recurrence and the need for reliable biomarkers. Chapter 6 evaluates the value of monitoring ANCA levels, revealing a moderately elevated odds of a disease relapse within 6 and 12 months of an ANCA rise. A larger effect was found by examining the odds of a positive test during an episode of recurrent inflammation. Collectively, this research enhances our comprehension of AAV's inflammatory cascade, offering prospects for enhanced diagnostics and targeted therapeutics.