AI Article Synopsis
- - This study investigates the roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis, focusing on their potential impact on disease progression and severity.
- - Researchers assessed blood and urine levels of these proteins in 42 AAV patients and discovered that higher levels were linked to more severe disease compared to inactive AAV or healthy controls.
- - The findings suggest that S100A8/A9 and S100A12 could be important biomarkers for AAV and may contribute to the disease's development through specific pathways in activated neutrophils.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9464401 | PMC |
| http://dx.doi.org/10.1186/s12865-022-00513-4 | DOI Listing |
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