Immune Cells Profiling in ANCA-Associated Vasculitis Patients—Relation to Disease Activity

Abstract

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of necrotizing multiorgan autoimmune vasculitides that predominantly affect small blood vessels and are associated with the presence of ANCAs. The aim was to assess regulatory and effector cell populations accompanied by the suPAR biomarker level and link the so-defined immune state to the AAV disease activity. The research involved a multicomponent description of an immune state encompassing a range of B and T cell subsets such as transitional/regulatory B cells (CD19+CD24++CD38++), naïve B cells (CD19+CD24INTCD38INT), Th17 cells, T regulatory cells (CD4+CD25+FoxP3+) and cytotoxic CD4+CD28− cells by flow cytometry. The suPAR plasma level was measured by ELISA. The results indicate that AAV is associated with an increased suPAR plasma level and immune fingerprint characterized by an expansion of Th17 cells and T cells lacking the costimulatory molecule CD28, accompanied by a decrease of regulatory populations (Tregs and transitional B cells) and NK cells. Decreased numbers of regulatory T cells and transitional B cells were shown to be linked to activation of the AAV disease while the increased suPAR plasma level—to AAV-related deterioration of kidney function. The observed immune fingerprint might be a reflection of peripheral tolerance failure responsible for development and progression of ANCA-associated vasculitides.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) in Autoimmune Rheumatic and Non Rheumatic Diseases

“…In 2021, Zabinska et al observed a statistically significant correlation between suPAR levels and kidney function in AAV with renal involvement associated with the immune activation state. So, the observed correlation between suPAR and the reported clinical characteristics may suggest that suPAR has the capacity to indicate renal involvement and disease severity [44].…”

“…The kidney is the most organ susceptible to the disease. MyeloPeroxidase (MPO) and PRoteinase 3 (PR3) are the two most significant target antigens of ANCAs, which are the serologic markers of AAV [44]. SuPAR is linked to kidney disorders and has been used to predict the progression of renal function loss.…”

Pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis

“…Abnormal activation of B cells was observed in AAV patients and was associated with disease severity or poor outcomes. [ 92 , 93 , 94 ] Clinical trials have shown that depletion of B cells with rituximab is a useful treatment for AAV. [ 41 , 42 ] All evidence suggests that B cells have a vital role in the pathogenesis of AAV.…”

Potential effects of shift work on skin autoimmune diseases

“…T cells play key roles in a variety of autoimmune diseases ( 239 , 240 , 247 , 250 , 258 , 260 ) and can enter and reside in the epidermis and dermis. Their recirculation between blood, lymphoid organs and other tissues is regulated by the circadian system ( 190 , 382 , 386 ) and by sleep ( 387 , 388 ).…”