Extracellular Vesicles Tune the Immune System in Renal Disease: A Focus on Systemic Lupus Erythematosus, Antiphospholipid Syndrome, Thrombotic Microangiopathy and ANCA-Vasculitis

Abstract

Extracellular vesicles (EV) are microparticles released in biological fluids by different cell types, both in physiological and pathological conditions. Owing to their ability to carry and transfer biomolecules, EV are mediators of cell-to-cell communication and are involved in the pathogenesis of several diseases. The ability of EV to modulate the immune system, the coagulation cascade, the angiogenetic process, and to drive endothelial dysfunction plays a crucial role in the pathophysiology of both autoimmune and renal diseases. Recent studies have demonstrated the involvement of EV in the control of renal homeostasis by acting as intercellular signaling molecules, mediators of inflammation and tissue regeneration. Moreover, circulating EV and urinary EV secreted by renal cells have been investigated as potential early biomarkers of renal injury. In the present review, we discuss the recent findings on the involvement of EV in autoimmunity and in renal intercellular communication. We focused on EV-mediated interaction between the immune system and the kidney in autoimmune diseases displaying common renal damage, such as antiphospholipid syndrome, systemic lupus erythematosus, thrombotic microangiopathy, and vasculitis. Although further studies are needed to extend our knowledge on EV in renal pathology, a deeper investigation of the impact of EV in kidney autoimmune diseases may also provide insight into renal biological processes. Furthermore, EV may represent promising biomarkers of renal diseases with potential future applications as diagnostic and therapeutic tools.

The functional role of soluble proteins acquired by extracellular vesicles

“…EVs may have a role in mediating inflammatory autoimmune disorders with a significant type III hypersensitivity component, including rheumatoid arthritis and systemic lupus erythematous, by contributing to the formation of antigen-immunoglobulin complexes (immune complexes) (Buzas et al, 2014;Mazzariol et al, 2021). Cloutier et al assessed the role of medium-sized EVs in the formation of immune complexes in rheumatoid arthritis, by using EVs isolated from the synovial fluid from patients with rheumatoid arthritis and EVs released by cultured platelets (Cloutier et al, 2013).…”

Extracellular vesicles in kidney disease

“…For example, in pre-eclampsia, placenta-derived extracellular vesicles carrying anti-angiogenic factors that are released into the maternal circulation might lead to glomerular endothelial dysfunction and proteinuria 34 . Circulating extracellular vesicles in autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome and ANCA-associated vasculitis, might promote coagulation, thrombosis and immune-mediated renal pathological conditions 35 .…”

The pathobiology of platelet and megakaryocyte extracellular vesicles: A (c)lot has changed

“…Several studies report an increase in PEV levels in SLE patients, which correlates with chronic platelet activation and thrombocytopenia that often occur in SLE. [43][44][45][46][47] Circulating PEVs can form immune complexes with immunoglobulins, which activate monocytes and increases levels of proinflammatory cytokines, including IL-1β, tumor necrosis factorα, and interferonα. 48 This enhancement in SLE pathology was concluded to occur because of the effect of PEV-immunoglobulin-G+ immune complexes on monocyte signaling, leading to inflammation and tissue damage.…”

“…Systemic lupus erythematosus (SLE) is an autoimmune disease characterized in part by an increase in autoantigens and immune complex deposition resulting in chronic inflammation and damage to tissues and organs. Several studies report an increase in PEV levels in SLE patients, which correlates with chronic platelet activation and thrombocytopenia that often occur in SLE 43–47 48 …”