Objective:To evaluate the clinical performance of anti-peptidylarginine deiminase 2 (PAD2) and anti-PAD4 antibodies combined testing in a Chinese rheumatoid arthritis (RA) cohort.Methods:A total of 148 RA inpatients and 35 patients with non-RA arthritis as controls (DC) were recruited from November, 2018 to November, 2019 in Peking University People′s Hospital. In addition, a total of 44 healthy controls (HC) who went to Peking University People′s Hospital for annual physical examination were collected from June 2019 to July 2019. The α-PAD2 and α-PAD4 level in clinical specimens were determined by ELISA. Statistical analysis was performed by the Mann-Whitney U test, the Kruskal-Wallis (KW) test, the χ 2 test or the Fisher′s Exact Test, as necessary. Correlation analysis were performed by logistic regression. Results:α-PAD2 and α-PAD4 were present in 26.4% (39/148) and 20.9% (31/148) patients with RA, 5.7% (2/35) and 5.7% DC (2/35) and 4.5% (2/44) and 2.3% HC (2/44), respectively. α-PAD4-positive RA patients displayed significantly longer disease duration compared to α-PAD4-negative RA patients (17.3±13.2 years vs 8.6±10.2 years, P<0.001). α-PAD4-positive RA patients showed a significantly higher incidence of interstitial lung disease (ILD) compared to those without α-PAD4 (54.8% vs 25.6%, P=0.002). No associations between α-PAD2 and ILD were found ( OR: 0.797, P=0.579). In contrast, significant associations between α-PAD4 and ILD were found ( OR: 3.521, P=0.002). In seropositive RA, α-PAD4 displayed a weak correlation with ILD ( OR: 2.324, P=0.046), but this association was greatly enhanced when combined with α-PAD2 [anti-PAD2 (-)] ( OR: 4.059, P=0.007). Conclusions:The findings delineate the clinical relevance of α-PAD2 and α-PAD4 in RA and suggest that the combined testing for α-PAD2 and α-PAD4 may provide additional diagnostic value to the current clinically available assays in RA, in particular in identifying patients at risk of RA-ILD.