Abstract: SA-PO107

Characterization of the Molecular Profile of the Kidney at the Initial Episode of Lupus Nephritis and at Renal Flare in the Same Patients

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
  • Shapiro, John P., 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
  • Song, Huijuan, 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

Renal flares are common in lupus nephritis (LN), and are generally treated in the same way as previous episodes of active LN. It is conceivable however, that after long-term immunosuppression the immune pathogenesis of a flare is different than the first episode of LN. We tested this hypothesis.

Methods

A cohort of 14 patients had kidney biopsies done at their first episode of LN, were successfully treated but subsequently flared and were biopsied again. These 28 pairs of renal biopsies were studied. LN class was the same between first and repeat biopsy. Glomeruli and tubulointerstitium (TI) were isolated by laser capture microdissection, RNA was extracted from each compartment and the expression of 578 immune-response genes was measured by Nanostring technology. Intra-renal transcript expression was compared between the first biopsy and the flare biopsy for each patient. Living transplant donor kidney biopsies at implantation (n=10) were used as normal controls.

Results

All patients were female and naïve to LN induction treatment at the time of the first biopsy. A principal component analysis did not show broad differences in gene expression between first and recurrent episodes of LN. However, glomeruli from flare biopsies demonstrated a significantly higher expression of complement pathway genes (CFH, C3, C1R, C1QB), TNF-regulated genes, and FN1, ITGA5, VCAM1 and IGF2R transcripts Conversely, in the TI there was lower expression of genes regulated by interferon-alpha 2 (CCL3, CXCL9, MX1, PML).

Conclusion

Although the expression of most immune genes was similar in the glomeruli and TI from initial and flare kidney biopsies, there were several differentially-expressed transcripts at flare. Knowledge of these differences may allow optimization of LN flare treatment, especially as targeted therapies become available.

Funding

  • Other NIH Support