Long Non-Coding RNA Negative Regulator of Interferon Response (NRIR): A Potential Marker for Disease Activity in Lupus Nephritis Patients

Abstract

Background: Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). Existing biomarkers lack consistent sensitivity, emphasizing the need for non-invasive alternatives. The long non-coding RNA NRIR (LncRNA-NRIR), an interferon-inducible molecule that downregulates type I interferon (IFN) signaling, may serve as a biomarker for SLE activity due to its association with IFN-driven immune activation.Objectives: To evaluate the relative expression (RE) of circulating lncRNAs-NRIR in peripheral blood mononuclear cells (PBMCs) of Egyptian patients with SLE and assess its association with LN activity.Patients and methods: This case-control study included 45 participants: 15 healthy controls (HC), 15 SLE patients with LN, and 15 Non-lupus nephritis (NLN) SLE patients. Circulating lncRNA-NRIR was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Clinical, laboratory, and disease activity indices were recorded and statistically evaluated.Results: The NRIR RE was significantly upregulated in LN patients compared with NLN and HC ( p<0.001). When both SLE groups were analyzed together, NRIR RE showed significant positive correlations with various markers of disease activity. Receiver operating characteristic (ROC) curve analysis of NRIR RE demonstrated excellent diagnostic performance in discriminating LN from NLN patients (AUC=0.871,95%CI=0.73–1.00), achieving 80% sensitivity and 93.3% specificity at a cutoff > 6.45 (fold change in relative expression). Multivariate regression confirmed NRIR RE (p=0.001) as an independent predictor of disease activity.Conclusion: Circulating lncRNA-NRIR is markedly upregulated in LN and correlates with disease activity. It effectively distinguishes SLE patients with nephritis and serves as an independent predictor of disease activity.