Background/Purpose: Lupus nephritis (LN), particularly, ISN/RPS class IV 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 PBMCs that correlate with LN disease activity. However, LN class-specific miRs have not been previously described.

Using deep-sequencing, we aimed to identify class-specific miRs in urine from adult and pediatric patients with biopsy-proven LN.

Methods: Cell-free urine from adult (n=25) and pediatric (n=8) female patients with ISN/RPS class III, IV (proliferative) and class 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 to limit batch effects and cost. Sequence reads were mapped to the human genome and small RNA databases. miRs were quantified by relative read abundance. qRT-PCR was used for quantitative validation.

Results: We had specimens from adult patients with distinct class III, IV, and V LN and pediatric patients with class III and IV. Samples from pediatric patients with class V LN were mixed with another class LN. We obtained reproducible miR profiles. In a paired-sample analysis we compared miR abundance in adult and pediatric active vs inactive LN, proliferative vs non-proliferative LN, class IV vs class III LN, active class III vs inactive class III LN, active class IV vs inactive class IV LN, and adult active class V vs inactive class V LN. In this analysis, we found significant changes in miR-324, -320, -200c (adult), -375 (pediatric), -200c, -30a, and -671*, respectively. All changes had a p value of <0.001, except for miR-30a (p=0.0011). Changes in miR abundance ranged from -11.8-log fold change to 11.3-log fold change.

Conclusion: In this study, we detected significant changes in miR abundance related to specific LN classes. Given that the prognosis of class IV LN is significantly worse than that of class III, identifying miRs that are associated with class IV LN is an important step in biomarker discovery of this particular aggressive form of LN. Identification of target genes of these miRs may open a venue for the discovery of new pathogenic pathways in this devastating disease.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/deep-sequencing-reveals-class-specific-urinary-micrornas-in-human-lupus-nephritis/