T-lymphocyte in ANCA-associated vasculitis: what do we know? A pathophysiological and therapeutic approach

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune condition that commonly causes kidney impairment and can be fatal. The key participation of B-lymphocytes as ANCA producers and neutrophils as target of these antibodies is widely described as the mechanism of endothelial damage in this disease. There has been a rising interest in the role of T-lymphocytes in AAV in recent years. Evidence is strong from animal models, and T-lymphocytes can be found infiltrating kidney tissue and other tissue sites in AAV patients. Furthermore, the different subsets of T-lymphocytes are also key players in the aberrant immune response observed in AAV. Polarization towards a predominant Th1 and Th17 response in the acute phase of the disease has been described, along with a decline in the number of T-regulatory lymphocytes, which, in turn, show functional impairment. Interactions between different T-cell subsets, and between T-cells and neutrophils and B-cells, also enhance the inflammatory response, constituting a complex network. Novel therapies targeting T-cell immunity are emerging in this scenario and may constitute an interesting alternative to conventional therapy in selected patients. This review aims to summarize the available evidence regarding T-cell imbalances and functional impairment, especially focusing on renal involvement of AAV.

Circulating B Cells, Plasma Cells, and Treg Associate with ANCA Levels in ANCA-associated Vasculitis

“…Exhausted T cells have been shown to be increased in AAV patients. 4 Although cells expressing exhaustion markers were also increased in AAV patients compared with HCs in our study, they were not significantly different than CKD controls, suggesting that such difference is shared across individuals with kidney impairment. We did not observe significant differences in cytokine production in phorbol myristate acetate plus ionomycin-stimulated T and B cells across the 3 study groups (data not shown).…”

Immunopathogenesis of ANCA-Associated Vasculitis

“…Th1 cells are overexpressed in ANCA-associated vasculitis, and during acute phases of the disease, it was demonstrated that a higher Th1/Th2 ratio corresponded to higher expression of IFN-γ in the kidneys [ 130 ]. Th1 polarization is mediated in ANCA-associated vasculitis by a decrease in CD28, a costimulatory signal which promotes Th2 differentiation [ 131 ]. Th1 effector cells promote the secretion of IFN-γ and IgG3, the strongest immunoglobulin subclass in inducing neutrophil activation.…”

Checkpoint inhibitor-related renal vasculitis and use of rituximab

“…23 Nonetheless, there is growing evidence of T lymphocytes' role in the pathogenesis of ANCA vasculitis, 24 25 and promoting the unopposed activity of these cells, as observed with CPI use, might explain to some degree the observed association between CPI use and renal vasculitis. [24][25][26] For example, CPIs can expand T cells (effector and follicular cells) and increase T and B cell interaction with potentially subsequent production of interferon gamma and interleukin 21-both cytokines have been previously reported to be associated with ANCA vasculitis. [27][28][29][30] CD4+ regulatory T cells (Tregs) are a highly immune-suppressive subset of CD4+ T cells and their expression of regulatory transcription factor FOXP3 is critical in maintaining self-tolerance.…”