A preliminary study on the change and clinical significance of peptidylarginine deiminase 4 expression on the neutrophils in the peripheral blood from the patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis / 中华风湿病学杂志

ABSTRACT

Objective:To investigate the change of peptidylarginine deiminase 4 (PAD4) expression in the neutrophils of peripheral blood of patients with anti-neutrophil cytoplasmic myeloperoxidase antibody-associated vasculitis (MPO-AAV), and to analyze the relationship between the change and disease activity.Methods:Thirty-nine untreated patients with active MPO-AAV (patient group) and thirty-nine healthy volunteers (control group) were enrolled into this study. The PAD4 expressed on neutrophils was detected by flow cytometry (FCM). The serum neutrophil extracellular traps (NETs), fragments from the activated complement C5 (C5a) and anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA) were measured by enzyme-linked immuno sorbent assay (ELISA). Their disease activity was evaluated by Birmingham vasculitis activity score (BVAS). All the detected results were compared between the 2 groups by t test, Spearman correlation analysis and multivariate linear regression analysis were employed to analyze the relationship between BVAS and the Lab test results in patient group. Results:The proportion of neutrophil expressing PAD4, the mean fluorescence intensity (MIF) of PAD4, the levels of NETs and C5a in patient group were significantly higher than those in the control group [(71±11)% vs (26±6)%, t=22.456, P<0.01; (33±4) vs (14±4), t=18.668, P<0.01; (0.62±0.22) vs (0.26±0.15), t=8.466, P<0.01 and (4.6±1.0) vs (2.9±1.0), t=7.697, P<0.01, respectively]. In patient group, BVAS was positively associated with the proportion of PAD4 + neutrophil, MFI of PAD4, the serum level of NETs, C5a and MPO-ANCA ( r=0.843, P<0.01; r=0.821, P<0.01; r=0.411 1, P<0.01; r=0.613, P<0.01 and P=0.790, P<0.01, respectively), however, the results of multiple linear regression analysis showed only the percentage of PAD4 + neutrophils and the level of MPO-ANCA were independent influencing factors on BVAS ( β=0.324 6, P<0.01 and β=0.796, P<0.01, respectively). Conclusion:The percentage of neutrophils expressed PAD4 in the peripheral blood of patient with active MPO-AAV is significantly increased, and it is an independent factor affecting the disease activity. Intervention on this expression might be a potential new pathway for MPO-AAV treatment.