Elevated Level of Serum Interleukin-21 and Its Influence on Disease Activity in Anti-Neutrophil Cytoplasmic Antibodies Against Myeloperoxidase-Associated Vasculitis

Xu, Junan; Zhao, Huanhuan; Wang, Sen; Zheng, Meijuan; Shuai, Zongwen

doi:10.1089/jir.2022.0014

Cited by 1 publication

(4 citation statements)

References 42 publications

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“…Circulating CD4 + CXCR5 + ICOS + Tfh cells were elevated and correlated with disease activity in patients with Henoch-Schönlein purpura (HSP) ( 72 ). The same results were observed in patients with active MPO-AAV ( 19 ) and Behcet’s disease ( 73 ). In patients with active AAV, the serum concentration of soluble ICOS was also higher than HCs ( 57 ).…”

Section: Co- Stimulatory Signal Pathwayssupporting

confidence: 78%

“…Compared to HCs, the expression intensity of PD-1 in Tfh cells was higher in patients with MPO-AAV. We also found that the expression of ICOS/PD-1 instead of PD-1 was associated with the levels of MPO-ANCA ( 19 ), indicating that co-stimulatory and co-inhibitory molecules were involved in the activation of T cells together. Although the fusion proteins containing an anti-PD-1 single-chain variable fragment could improve symptoms of type 1 diabetes (TID) and EAE models ( 132 ), its effects in AAV have yet to be explored.…”

Section: Co-inhibitory Signal Pathwaysmentioning

confidence: 78%

“…Several studies focused on the differences of ICOS + Tfh cells in vasculitis ( 19 , 72 , 73 ). Circulating CD4 + CXCR5 + ICOS + Tfh cells were elevated and correlated with disease activity in patients with Henoch-Schönlein purpura (HSP) ( 72 ).…”

Section: Co- Stimulatory Signal Pathwaysmentioning

confidence: 99%

“…T cells play essential and pivotal roles in autoimmunity. Studies have revealed that subgroups of T cells, including regulatory T cells (Treg) and helper T cells (Th), especially follicular Th cells (Tfh), Th2 and Th17, were involved in the pathogenesis of AAV ( 16 – 19 ). The exhaustion of T cells could predict the favorable prognosis of AAV ( 20 ).…”

Section: Introductionmentioning

confidence: 99%

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Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future

et al. 2023

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Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T‐cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV.

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