Objective To explore the expression and significance of neutrophil extracellular traps(NETs)in peripheral blood of primary Sj?gren's syndrome(pSS)patients across different disease activity levels,and the predictive value of NETs and routine laboratory markers antithrombin Ⅲ(AT Ⅲ),alkaline phosphatase(ALP)and carbohydrate antigen 125(CA125)for pSS disease activity.Methods A total of 94 newly diagnosed pSS patients at the Affiliated Lianyungang Hospital of Xuzhou Medical University from October 2021 to December 2023 were categorized into active(n=49)and non-active(n=45)groups based on the European League Against Rheumatism(EULAR)Sj?gren's Syndrome disease activity index(ESSDAI).The levels of NETs biomarkers,namely serum myeloperoxidase(MPO)-DNA,were measured using ELISA.Laboratory routine indicators and MPO-DNA were integrated into multivariate Logistic regression to screen for independent influencing factors of pSS disease activity.Pearson's correlation was used to evaluate the relationship between MPO-DNA levels and ESSDAI scores.The efficacy of MPO-DNA alone or in combination with AT Ⅲ,ALP and CA125,for predictors of disease activity was evaluated using ROC curve.Results Serum MPO-DNA(23.884±3.494 μg/L),ALP(80.159±34.318 U/L)and CA125(20.300±16.560 U/ml)levels of active pSS patients were higher than those in the non-active patients(19.024±3.324 μ g/L,67.500±21.166U/L,13.200±6.340 U/ml),while AT Ⅲ(89.180±15.040 ng/ml)was lower than that in non-active patients(94.650±11.620 ng/ml),with significant differences(t=-7.921,-2.426,-2.925,2.094,all P＜0.05).Multivariate Logistic regression analysis showed laboratory indicator MPO-DNA,ALP and CA125 were independent risk factors,while AT Ⅲ was an independent protective factor(all P＜0.05).MPO-DNA was positively correlated with ESSDAI scores(r=0.602,P＜0.01).The AUC(95％CI)of the combination of ALP,CA125 and AT Ⅲ for predicting disease activity in pSS was 0.711(0.612～0.810).The AUC(95％CI)of MPO-DNA alone for predicting disease activity in pSS was 0.837(0.758～0.915),and the AUC(95％CI)of combination of MPO-DNA,ALP,CA125 and AT Ⅲ for predicting disease activity in pSS was 0.866(0.797～0.935),showing an improving in the predictive value.Conclusion The involvement of NETs in the occurrence and expression levels of pSS is related to its disease activity.NETs combined with ALP,CA125 and AT Ⅲ have effective diagnostic performance for the disease activity of pSS.This tool can serve as a biological indicator for predicting the disease activity of pSS.