Deep-sequencing reveals WHO class-specific urinary microRNAs in human lupus nephritis (P3245)

Abstract

Abstract Lupus nephritis (LN) is associated with significant morbidity and mortality. microRNAs (miRs) are small, non-coding RNAs that regulate translation. Previous, studies report changes in miR expression in kidney tissue, urine and PBMC that correlate with LN disease activity. However, LN WHO class-specific miRs have not been described. Using deep-sequencing, we aimed to identify WHO class-specific miRs in urine from adult and pediatric patients with biopsy-proven LN. Cell-free urine from adult (n=25) and pediatric (n=8) female patients with WHO class IV and V LN were obtained at time of active disease and during remission. Total RNA was used to prepare small RNA cDNA libraries for sequencing. Multiplexing through sample-specific 3' adapters was applied. Sequence reads were mapped to the human genome and small RNA databases. miRs were quantified by relative read abundance. We obtained reproducible profiles of miRs. In a paired-sample analysis comparing miR abundance in urine of adult and pediatric patients with active class IV versus class V LN, we found significant changes in 6 miRs, including up-regulation of miR-193a-5p, -423, 501-3p, and -874 by 400-1,000x in WHO class IV LN. In conclusion, we detected higher counts of specific miRs in urine of adult and pediatric patients with LN class IV, versus class V. Given the worse prognosis of class IV LN identifying miRs associated with this LN class is an important step in biomarker discovery of this particulary aggressive disease.