[The expression and clinical significance of neutrophil myeloperoxidase in patients with myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis].

ABSTRACT

Objective: To investigate the expression and clinical significance of neutrophil myeloperoxidase (MPO) in patients with MPO-antibody associated vasculitis (AAV). Methods: Thirty-six newly diagnosed MPO-AAV patients who were hospitalized in the First Affiliated Hospital, Anhui Medical University from July 2018 to June 2021 were enrolled,and 36 age and sex matched healthy subjects were selected as controls. Neutrophil MPO level was detected by flow cytometry (FCM) and MPO mRNA was tested by real time quantitative polymerase chain reaction (RT-qPCR) in all subjects. Serum complement fragment C5 (C5a) and MPO in both groups and serum MPO-anti-antineutrophilic cytoplasmic antibody(ANCA) in MPO-AAV group were measured by enzyme linked immunosorbent assay (ELISA), while the disease activity was evaluated by Birmingham vasculitis activity score-V3 (BVAS-V3). Results: Compared with the heathy control group, the expression of MPO mRNA in neutrophils, serum MPO and complement C5a in MPO-AAV group were significantly higher[MPO mRNA30.2±11.5 vs. 1.9±0.6, P<0.001;MPO(112.0±68.7) IU/L vs. (87.4±22.9) IU/L, P=0.01; C5a(187.3±90.3) ng/ml vs. (107.3±31.1) ng/ml, P<0.001; respectively], while the mean fluorescence intensity (MFI) of MPO in neutrophils were significantly lower [ 1 343.3±723.4 vs. 2 868.0±1 136.5, P<0.001]. In MPO-AAV group, the expression of neutrophil MPO mRNA was positively correlated with serum MPO-ANCA and MPO levels (r=0.537, P=0.001 and r=0.358, P=0.032; respectively). Multiple regression analysis suggested that neutrophil MPO mRNA expression was positively correlated with serum MPO-ANCA level (ß=0.695, P=0.006); neutrophil MPO level was negatively correlated with serum MPO-ANCA, MPO and complement C5a levels (r=-0.335, P=0.046; r=-0.372, P=0.026; r=-0.577, P<0.001; respectively). Further, neutrophil MPO level was negatively correlated with serum complement C5a level (ß=-0.374, P=0.043). BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils, serum MPO-ANCA, MPO and complement C5a (r=0.598, P<0.001; r=0.599, P<0.001; r=0.537, P=0.001; r=0.415, P=0.012; respectively) and negatively correlated with MPO level in neutrophils (r=-0.342, P=0.041). In multiple regression analysis it suggested that BVAS-V3 was positively correlated with MPO mRNA expression in neutrophils (ß=0.511, P=0.002). Conclusion: In MPO-AAV patients, MPO synthesis and release in neutrophils are both significantly increased, which might be influenced by serum MPO-ANCA and C5a, respectively. Furthermore, MPO synthesis activity in neutrophils is an independent factor related to disease activity.