Kidney Week

Abstract: TH-PO0325

Integrative Small RNA and Transcriptomic Profiling of Formalin-Fixed Paraffin Embedded Kidney Biopsies from a Lupus Nephritis Inception Cohort Reveals Novel and Clinically Relevant MicroRNA Signatures

Session Information

• Glomerular Diseases: Omics
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Shumway, Alexandria, The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Alexandria Shumway, PhD

• Arias, Antonio, The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Antonio Arias

• Derebail, Vimal K., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Vimal K. Derebail, MD, MPH, FASN

• Saxena Beem, Shruti, The University of North Carolina at Chapel Hill Thurston Arthritis Research Center, Chapel Hill, North Carolina, United States

Shruti Saxena Beem

• Gartner, Valerie, The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Valerie Gartner, PhD

• Schaner, Matthew, The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Matthew Schaner

• Poulton, Caroline J., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Caroline J. Poulton, MSW

• Hogan, Susan, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Susan Hogan, PhD, MPH

• Saha, Manish K., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Manish K. Saha, MD

• Gibson, Keisha L., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Keisha L. Gibson, MD, MPH, FASN

• Jennette, John Charles, The University of North Carolina at Chapel Hill Department of Medicine, Chapel Hill, North Carolina, United States

John Charles Jennette, MD, FASN

• Falk, Ronald, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Ronald Falk, MD, FASN

• Sethupathy, Praveen, Cornell University College of Veterinary Medicine, Ithaca, New York, United States

Praveen Sethupathy, PhD

• Furey, Terrence, The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Terrence Furey, PhD

• Sheikh, Saira Z., The University of North Carolina at Chapel Hill Thurston Arthritis Research Center, Chapel Hill, North Carolina, United States

Saira Z. Sheikh, MD

• Sheikh, Shehzad Z., The University of North Carolina at Chapel Hill Center for Gastrointestinal Biology and Disease, Chapel Hill, North Carolina, United States

Shehzad Z. Sheikh, MD

Background

Lupus nephritis (LN) is a severe and life-threatening complication of systemic lupus erythematosus (SLE) for which existing clinical tests fail to reliably predict disease progression or long-term renal outcomes. Formalin-fixed paraffin-embedded (FFPE) biopsy specimens archived in clinical biobanks represent an underutilized resource for molecular discovery.

Methods

The Multi-Omic iNtegrated Analysis of Lupus (MONA Lupus) project leveraged the Glomerular Disease Collaborative Network's (GDCN) LN inception cohort (N=95) to perform RNA sequencing (RNA-seq) and small RNA sequencing (smRNA-seq) on FFPE kidney biopsies obtained at diagnosis. Only LN patients with available FFPE and concurrent blood samples were included. FFPE tissue from zero-hour renal transplant biopsies were used as healthy controls (N=31).

Results

RNA-seq analysis demonstrated that FFPE-derived transcriptional signatures successfully stratify normal kidney from LN, validating Type I interferon signaling, inflammatory macrophage activation, and extracellular matrix remodeling as key pathogenic pathways consistent with emerging molecular signatures identified through the Accelerating Medicines Partnership (AMP) consortium. Integrative smRNA-seq identified 41 differentially expressed (DE) microRNAs shared across LN classifications versus controls (baseMean >500, |log2FC| >0.75, padj <0.05). Notably, miR-142-5p, miR-150-5p, and miR-155-5p emerged as DE across all comparisons and are predicted to function as master regulators of T-cell, B-cell, and innate immune responses by targeting immune genes. miR-21-5p and miR-22-3p were identified as additional master regulators, with established roles in SLE disease activity and LN pathogenesis. miR-146b-5p, uniquely DE between proliferative (Class III/IV) and membranous (Class V) LN, targets the TLR4/IRAK1/TRAF6 axis and serves as a class-discriminating biomarker.

Conclusion

Integrative RNA-seq and smRNA-seq on FFPE biopsies from an LN inception cohort yielded mechanistically grounded master regulatory miRNAs and novel class-specific candidates with direct implications for prognostic stratification and therapeutic targeting in LN.

Acknowledgment

We would like to acknowledge Dr. Richard Loeser, Director of the UNC Thurston Arthritis Research Center, for his leadership and support. This project was supported by the Fund for Excellence in Lupus & Sjogren's and the Virginia A. and Douglas R. Ware Fund for Excellence in Autoimmune Diseases at the UNC Thurston Arthritis Research Center.