Comparison of Renal Transcriptome Profiles in Patients with Active Lupus Nephritis Reveals Possible New Mechanisms of Disease Progression

To identify factors that influence the progression of lupus nephritis (LN), we performed RNA sequencing on renal biopsy samples obtained from patients with active LN. The renal biopsy pathology followed the classification of the International Society of Nephrology and Renal Pathology Society (ISN/RPS) for 21 lupus nephritis patients: 2 in Class II, 3 in Class III, 10 in Class IV, 5 in Class V, and 1 patient with mixed type LN. The duration of disease from onset of systemic lupus erythematosus (SLE) to the onset of lupus nephritis was 26 months. Proteinuria was 2.5 (g/gCr or g/24hr), estimated Glomerular Filtration Rate (eGFR) was 72.9 (ml/min/1.73 m2), Index of activity was 5, and Index of chronicity was 3. Among different gene expression variations, the type I interferon (IFN) signature showed high expression in patients with shorter disease duration, preserved eGFR, and lower Index of chronicity. The type I IFN signature contributes to fibrosis in the tubulointerstitial space and worsens chronic lesions. Early control of the type I IFN signature may limit disease progression. Our results reveal a potential molecular mechanism for active LN and the link between functional and structural changes and differential gene expression observed in patients with early-stage LN. Overall design: Twenty-one patients with lupus nephritis (LN) proven by renal biopsy who were admitted to Nagasaki University Hospital between January 2012 and May 2018 were enrolled in this study.RNA-seq was performed on 21 LN samples.