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Abstract: SA-OR045

Molecular Profiling of Serial Kidney Biopsies to Identify Markers That Predict Long Term Outcomes in Lupus Nephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

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
  • Lococo, Bruno Jorge, Hospital Fernandez, Buenos Aires, Argentina
  • 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
  • Fadda, Paolo, 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
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background

Proliferative lupus nephritis (LN) is treated with induction therapy followed by prolonged maintenance therapy for several years. The intra-renal molecular changes that occur during this treatment period is unknown. Here we present results of molecular profiling of the LN glomeruli using protocol kidney biopsies to identify markers of long term response.

Methods

A protocol kidney biopsy was done at flare (Bx1), after induction therapy (Bx2) and after 3 years of maintenance therapy (Bx3) in 9 LN patients. Controls were living donor transplant biopsies (n=6). Glomeruli were laser dissected and RNA was extracted and analyzed by nanostring. Transcript expression from LN glomeruli was compared to controls, and complete responders (CR, n=5) were compared to non-responders (NR, n=4). Response was determined by proteinuria level and renal function at Bx3. All patients were treated with standard induction and maintenance therapy for LN.

Results

There were 110 differentially expressed glomerular transcripts between NR and CR. Pathway analysis revealed upregulation of several T cell pathways in NR compared to CR including Th1, Th2, NFAT, ICOS-ICOSL, CD28 and PKC signaling in T lymphocytes. Additionally, toll-like receptor, trem1, complement, and interferon signaling were upregulated in NR. The expression of 8 glomerular transcripts significantly increased in NR and decreased in CR from Bx1 to Bx3. This included HLA-DQA1 (FC:3.9 P: 0.03), LAIR1 (FC:4.2, P:0.004), GBP1 (FC:2.7, P:0.001), CCR1 (FC: 3.4 P:0.04), JAK1 (FC:2.0 , P:0.02), C1R (FC:2.5 , P:0.01), CTSC (FC:2.6 , P:0.04), and C1QA (FC:4.2, P:0.01).

Conclusion

Transcript expression from serial kidney biopsies in LN after prolonged maintenance therapy predicts T cell activation and persistent inflammation in NR compared to CR glomeruli. These pathways could be specifically targeted to improve response in NR. Several glomerular transcripts were identified to predict response in this cohort. These transcripts should be studied further to determine their utility as predictive markers of long-term outcomes in LN.

Funding

  • NIDDK Support