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Significance of Gasdermin-D in the Incidence of ANCA-Associated Vasculitis
Authors:  Ran Liu, M.M., Xiaojuan Guo, M.M., Luling Li, M.D., Yongfeng Zhang, M.D., Xin Dong, M.D., Qiang Fu, M.D., and Yi Zheng, M.D.
  Objective: To explore the involvement of GSDMD in the pathogenesis of antineutrophil cytoplasmic antibodies (ANCA)–associated vasculitis (AAV) through neutrophil extracellular traps (NETs). It is currently believed that the pathogenesis of AAV is caused by the direct pathogenic effects of ANCAs and NETs. The latest study found that the perforation activity of GSDMD is the key to inflammatory cell death and participates in regulating the formation of NETs.
Study Design:
The clinical data of patients with AAV were collected, and their serum DNA/NET concentration (prompt NETs level) and GSDMD concentration were detected. Comparison of measurement data between groups used t test or Mann-Whitney U test, and count data used χ2 test or Fisher’s exact test. Spearman rank correlation analysis was used to analyze the correlation between serum GSDMD and other continuous variables.
Serum GSDMD level and DNA/NETs level has nothing to do with age. Serum GSDMD level and DNA/NETs level in the AAV group were higher than the control group. Serum GSDMD level in AAV active disease group was higher than AAV stable disease group. AAV active disease group serum GSDMD level was positively correlated with neutrophil ratio and CRP level, and negatively correlated with serum albumin level and hemoglobin level. AAV serum GSDMD level was positively correlated with serum DNA/NETs level. There was no correlation between GSDMD level and DNA/NETs level and ANCA antibody level. ANCA antibody has nothing to do with AAV disease activity status.
Serum gasdermin D levels and serum DNA/NETs levels in AAV patients are related to the pathogenesis of AAV and provide a specific experimental basis for the impact of GSDMD and NETs in the pathogenesis of AAV. The increase of serum GSDMD in AAV patients may be related to disease activity status. Serum ANCA antibodies cannot indicate the active state of AAV disease.
Keywords:  antineutrophil cytoplasmic antibodies, ANCA-associated vasculitis, gasdermin D, GSDMD, NETosis, vasculitis
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