Abstract: SA-PO102

Characterizing the Glomerular Immune Response to Induction Therapy in Lupus Nephritis (LN) through Molecular Imaging of Serial Kidney Biopsies

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Parikh, Samir V., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Fadda, Paolo, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Eadon, Michael T., Indiana University Division of Nephrology, Indianapolis, Indiana, United States
  • Birmingham, Daniel J., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Malvar, Ana, HOSPITAL FERNANDEZ, Buenos Aires, Argentina
  • Song, Huijuan, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Shapiro, John P., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Alberton, Valeria Gabriela, hospital Fernandez, Buenos Aires, Argentina
  • Mejia-Vilet, Juan M., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Ayoub, Isabelle, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Satoskar, Anjali A., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Zhang, Jianying, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
Background

The effects of LN therapy on the molecular profile of kidney is unknown. To address this question we examined the glomerular transcriptomes before and after induction therapy.

Methods

Patients with proliferative LN (n=56) were diagnosed by kidney biopsy (Bx1), treated with steroids plus cyclophosphamide (CYC) or mycophenolate (MMF) and re-biopsied after induction (Bx2). At Bx2 14 CYC and 13 MMF patients achieved a complete renal response (CR) and 6 CYC and 3 MMF patients had no response (NR). Glomeruli were isolated by laser capture microdissection and RNA was analyzed by Nanostring technology. Transcript expression was compared between Bx1 and Bx2 for each group. Only transcripts with at least 2-fold change (FC) and p<0.01 were considered differentially-expressed.

Results

After treatment, transcripts that were differentially overexpressed at Bx1 decreased in expression at Bx2 in CR treated with CYC or MMF. This included significant downregulation of pro-inflammatory, complement and fibrosis genes including FCER1G, C1QB, CCL2, FN1, and TGFBI. Conversely, NR after CYC showed persistent overexpression of transcripts upregulated at Bx1 and increased expression of additional transcripts including CR1 (FC: 2.0, P=0.001), C8G (P=2.1, FC=0.002), MIF (FC-2.0, P=0.009), STAT6 (FC: 1.9, P=0.0009) and LGALS3 (FC: 1.9, P=0.005). NR after MMF also showed persistent overexpression of transcripts upregulated at Bx1 but also increased expression of over 20 additional transcripts, including dendritic cell, neutrophil, and NK cell signatures, such as IL3 (FC: 2.5, P=0.0004), CSF2RB (FC: 3.1, P=0.0001), KLRF1 (FC: 3.4, P=0.0003), TNFSF12 (FC: 2.7, P=0.001), IL21R (FC: 3.5, P=0.0003), FN1 (FC:3.9, P=0.001), and LAMP3 (FC:2.2, P=0.0003).

Conclusion

The glomerular immune signature in NR after MMF therapy is different than after CYC. These data suggest that different approaches may be needed to rescue NR depending on choice of induction treatment.

Funding

  • Other NIH Support