Abstract: SA-PO101

Molecular Profiling of the Kidney Biopsy in Class V Lupus Nephritis: Implications for Therapy

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Mejia-Vilet, Juan M., Ohio State University Wexner Medical Center , Columbus, United States
  • Parikh, Samir V., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Fadda, Paolo, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Uribe-uribe, Norma O., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
  • Shapiro, John P., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Yu, Lianbo, Ohio State University Wexner Medical Center , Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center , Columbus, Ohio, United States
Background

Class V lupus nephritis (LN) is often grouped with proliferative LN in clinical trials of experimental therapeutics. Given its distinctly different histology there is concern that class V patients may confound trial results of proliferative LN. We used molecular profiling of the kidney biopsy to identify potential differences in the immune pathogenesis of class V LN and proliferative LN.

Methods

Kidney biopsies from 21 patients having their first episode of LN were used. The glomeruli and tubulointerstitium (TI) were isolated by laser capture microdissection. RNA was extracted from each compartment and a panel of 578 immune-response genes was measured by Nanostring. Transcript expression was compared between proliferative (PF; classes III/IV) LN (n=7), membranous (MLN, class V) LN (n=5) and mixed (MT, classes III/IV+V) LN (n=9). Living transplant donor kidneys (n=10) were used as normal controls (NC).

Results

Principal component analysis showed clustering of patients by LN class in both renal compartments, but this was particularly striking for MLN and NC groups. A total of 42, 29 and 8 genes were differentially expressed in the glomeruli between MLN and MT, MLN and PF and MT and PF groups, respectively. Interferon-α2 (IFNA2)-regulated genes had higher expression in MLN glomeruli compared to MT and PF glomeruli. In contrast, 20 transcripts regulated by TGF-b1 had lower expression in MLN glomeruli compared to MT. In the TI, a total of 108, 21 and 25 genes were differentially expressed between MLN and MT, MLN and PF and MT and PF. In par ticular, transcripts regulated by IL-3 and IL-18 had higher expression in MLN than MT.

Conclusion

MLN has a distinctive gene expression pattern when compared to MT and PF LN which likely reflects a different pathogenesis. This has implications for treatment and for inclusion in clinical trials of experimental therapeutics.

Funding

  • Other NIH Support