Long non-coding RNA expression profiles in neutrophils revealed potential biomarker for rapidly progressive interstitial lung disease in MDA5+ dermatomyositis

OBJECTIVES: The long non-coding RNAs play important roles in the pathogenesis of autoimmune rheumatic diseases. This study aims to screen and identify dysregulated lncRNAs in neutrophils of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (MDA5+DM) and explore the relationship between candidate lncRNA levels and well-recognised disease activity-related indicators. METHODS: RNA-Seq was used to identify differentially expressed lncRNAs in neutrophils from MDA5+DM, Jo1+ASyS and healthy controls. Following the screening process, levels of the candidate lncRNAs were confirmed using real-time quantitative polymerase chain reaction in 280 participants, including 103 MDA5+DM, 85 Jo1+ASyS, 12 MDA5-DM, 26 SLE, 54 healthy controls. RESULTS: LncRNA expression profiling analysis identified 412 up-regulated and 201 down-regulated lncRNAs in neutrophils of MDA5+DM compared to healthy controls. Moreover, 144 lncRNAs were up-regulated, and 191 lncRNAs were down-regulated between MDA5+DM and Jo1+ASyS. RT-qPCR assay confirmed that the level of Lnc-ZCCHC13-18:1 was significantly higher in neutrophils of MDA5+DM compared to MDA5-DM, Jo1+ASyS, SLE, and healthy controls (all p-values <0.001). Notably, Lnc-ZCCHC13-18:1 (OR: 9.94, 95%CI: 2.71-47.12, p=0.001) was identified as an independent risk factor for RPILD, along with other well-recognised risk factors, such as the percentage of predicted diffusing capacity for carbon monoxide (OR: 6.23, 95%CI: 1.88-24.29, p=0.004), Krebs von den Lungen-6 (OR: 4.26, 95%CI: 1.31-15.63, p=0.02), serum ferritin (OR: 6.14, 95%CI: 1.75-26.41, p=0.008) and age at admission (OR: 1.07, 95%CI: 1.01-1.13, p=0.031). CONCLUSIONS: LncRNA expression profiling in neutrophils of MDA5+DM revealed differentially expressed lncRNAs. Lnc-ZCCHC13-18:1 has been identified as a possible biomarker for RPILD in MDA5+DM.