The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis

Abstract

Objectives. T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self-harming immune responses and prevent the development of autoimmune diseases. In anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice-variant lacking exon 2 in T cells (FOXP3D2 CD4 + T cells). However, the suppressive capacity of Tregs varies between subsets. We evaluated the frequency of Treg subsets in ANCA vasculitis as a potential explanation for diminished suppressive capacity. Methods. We developed a custom mass cytometry panel and performed deep immune profiling of Tregs in healthy controls, patients with active disease and in remission. Using these data, we performed multidimensional reduction and discriminant analysis to identify associations between Treg subsets and disease activity. Results. Total Tregs were expanded in ANCA vasculitis, which was associated with remission and the administration of rituximab and/or prednisone. The frequency of FOXP3D2 CD4 + T cells did not distinguish disease activity and this population had high expression levels of CD127 and lacked both CD25 and Helios, suggesting that they are not conventional Tregs. The frequency of CXCR3 + , CD103 + and CCR7 + Tregs distinguished disease activity, and the combination of the frequency of these three Treg subsets segregated active patients from patients in remission and healthy controls. From these three subsets, the frequency of CXCR3 + Tregs distinguished patients with active disease with renal involvement. Conclusion. Treg heterogeneity can discriminate disease activity and should be explored as a biomarker of disease activity in ANCA vasculitis.

Causal relationship between immune cells and the risk of myeloperoxidase antineutrophil cytoplasmic antibody‐associated vasculitis: A Mendelian randomization study

“…Research has shown that MPO + ANCA EGPA is associated with an increased count of three immunophenotypes in the Treg panel. In AAV, there is an increase in the count of Tregs 22 . However, during the progression stage, the expression of CD8+ CD25+ Tregs is downregulated and plays a crucial role in maintaining immune tolerance and regulating immune responses 48 .…”

“…Observational studies have found that functional defects in Tregs are associated with various human autoimmune diseases 20,21 . In the case of AAV, a significant decrease in the proportion of activated Tregs was discovered, along with a reduction in their cellular functionality 22 . Research has indicated that heightened disease activity in EGPA is linked to decreased levels of Tregs 23 .…”

“…discovered, along with a reduction in their cellular functionality. 22 Research has indicated that heightened disease activity in EGPA is linked to decreased levels of Tregs. 23 Tregs have a protective function to prevent the development of autoimmune diseases by maintaining immune homeostasis and peripheral tolerance.…”

“…In AAV, there is an increase in the count of Tregs. 22 However, during the progression stage, the expression of CD8+ CD25+ Tregs is downregulated and plays a crucial role in maintaining immune tolerance and regulating immune responses. 48 Additionally, CD39+ Tregs can attenuate the chronic and persistent T-cell activation commonly observed in AAV, potentially contributing to the remission phase of the disease.…”

Update on antineutrophil cytoplasmic autoantibody vasculitis in children

“…T regulatory cells (Tregs), which dampen immune responses, are expanded in AAV patients in remission. Tregs subsets may distinguish disease activity with expanded CD103þ and CCR7þ subsets and decreased CXCR3þ subsets during active disease [8]. B-cell autoreactivity and autoantibody production are also important in AAV pathogenesis.…”