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Abstract: TH-OR068

Molecular Profiling of Renal Compartments from Serial Lupus Nephritis Kidney Biopsies to Identify Markers of Response

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Parikh, Samir V., 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
  • Yu, Lianbo, 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 Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

Molecular profiling of kidney compartments from serial renal biopsies of proliferative lupus nephritis (LN) may provide novel information to improve treatment. Here we present results of molecular profiling of the glomeruli and tubulointerstitum (TI).

Methods

A kidney biopsy was done at flare (Bx1) and after induction therapy (Bx2) in 56 LN patients. Controls were living donor transplant biopsies (n=7). Glomeruli and TI were isolated using laser capture microdissection, RNA was extracted and analyzed by Nanostring. Transcript expression of LN flares was compared to controls, and complete renal responders (CR, n=28) were compared to non-responders (NR, n=9).

Results

The top upregulated glomerular transcripts were TGFBI(fold-change (FC): 10.6, P=6x10-9), FCER1G (FC:8.2, P=2x10-7), CCL2(FC:3.5, P=0.001), FN1(FC:3.5, P=2x10-7), ICAM1(FC:3.2, P=0.0001) and VCAM1 (FC:2.7, P=6x10-13). The top upregulated TI transcripts were CCR10(FC:2.8, P=5x10-9), STAT1(FC:2.8, P=6x10-8), HLA-DRB3(FC:2.6, P=2x10-12), CCL19(FC:2.8, P=2x10-7), CD74(FC:2.3, P=1x10-15) and CFD(FC:2.2, P=0.00001). At Bx1 26 glomerular and 39 TI transcripts differentiated CR from NR. After treatment several glomerular and TI transcripts differentially-expressed in Bx1 trended toward control levels in Bx2, but 15 transcripts significantly increased in expression, suggesting increased infiltration of T cells (CD5, CD7, ICOS, CD45), NK cells (CD2, KLRB1), and neutrophils (CSF3RB) in NR TI.

Conclusion

The inflammatory profiles of glomeruli and TI at LN flare and after treatment are different. CR and NR also have unique profiles at flare that may be helpful in predicting response to therapy. After treatment NR are characterized by increased infiltration of T cells, NK Cells and neutrophils in the TI compared to CR. These transcripts may be used to refine subsequent treatment of NR and convert these patients to CR.

Funding

  • Other NIH Support