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The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.


ABSTRACT:

Background

The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis.

Methods

Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1β, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated.

Results

The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1β, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils.

Conclusion

S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis.

SUBMITTER: Bai X 

PROVIDER: S-EPMC9464401 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis.

Bai Xue X   Xu Peng-Cheng PC   Chen Tong T   Zhang Hao-Miao HM   Wu Si-Jing SJ   Yang Xia X   Gao Shan S   Jia Jun-Ya JY   Jiang Jian-Qing JQ   Yan Tie-Kun TK  

BMC immunology 20220910 1


<h4>Background</h4>The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis.<h4>Methods</h4>Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apopto  ...[more]

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