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Abstract: FR-PO848

Peripheral Blood RNA Signatures for Active Kidney Injury in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Zhang, Xiaolan, Ohio State University, Columbus, Ohio, United States
  • Greco, Jessica M., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Zhang, Li, Ohio State University, Columbus, Ohio, United States
  • Nadasdy, Tibor, Ohio State University, Columbus, Ohio, United States
  • Fadda, Paolo, Ohio State University, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

Because lupus nephritis (LN) is a manifestation of a systemic process it is reasonable to ask whether circulating leukocytes can serve as a source of biomarkers of active kidney disease. To begin to examine this question we characterized the immune transcriptome of peripheral blood cells at the time of kidney biopsy and looked for associations with renal histology.

Methods

We studied 44 patients with SLE and kidney biopsies consistent with LN, 9 patients with IgAN as immune complex disease controls, and 5 healthy controls. Total RNA was extracted from buffy coats collected at the time of kidney biopsy and tested on a customized gene expression nCounter GX CodeSet. The Nano-String raw data were analyzed with nSolver™ 4.0 software and JMP 14 pro statistical program. Differential expression of significant transcripts was further confirmed by TaqMan gene expression real-time RT-PCR. The NIH activity (AI) and chronicity (CI) indices of the patients’ kidney biopsies were scored by a renal pathologist.

Results


Compared to healthy and disease controls 57 out of 199 transcripts were overexpressed in LN patients. Of these, 25 genes were significantly increased 2-fold or more in active LN (P<0.0001). Over half of these 25 genes are involved in type I interferon signaling. Other differentially-activated pathways included cytokine-mediated responses, B-cell activation and apolipoprotein metabolism. The top overexpressed transcripts in LN were IFI27, CD169, LAMP3 and DNAPTP6 which were 49, 21, 18 and 12-fold higher than healthy and disease controls. PCR confirmed these RNA signatures with IFI 243-fold and CD169 24-fold higher than disease controls. AI correlated positively with APOEBC3A and IL-1A (both R2=0.19) and negatively with TRADD (R2=0.31), while MIP-1a (R2=0.2368) positively correlated with CI (all, P<0.01).

Conclusion

Interferon-I signaling, cytokine response, B-cell activation and lipoprotein metabolism are the major differentially-activated in peripheral blood cells during LN flares. AI and CI correlates are mainly cytokines, mediators of innate immunity, and apoptosis.

Funding

  • Clinical Revenue Support