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Abstract: TH-PO829

Molecular Profiling of the Kidney in Lupus Nephritis (LN) to Identify Heterogeneity in Different Races and Ethnicities

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Ayoub, Isabelle, Ohio State University Medical Center, Columbus, Ohio, United States
  • Malvar, Ana, HOSPITAL FERNANDEZ, Buenos Aires, Argentina
  • Parikh, Samir V., Ohio State University Medical Center, Columbus, Ohio, United States
  • Song, Huijuan, Ohio State University, Upper Urlington, Ohio, United States
  • Shapiro, John P., Ohio State University, Columbus, Ohio, United States
  • Fadda, Paolo, Ohio State University, Columbus, Ohio, United States
  • Yu, Lianbo, Ohio State University, Upper Urlington, Ohio, United States
  • Satoskar, Anjali A., Ohio State University, Upper Urlington, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
Background


Black and Hispanic LN patients have worse kidney outcomes than white patients. Beyond socioeconomic status, we postulated that differential activation/inactivation of molecular pathways during LN flare may contribute to this racial and ethnic difference. To test this hypothesis we examined the intrarenal transcript profiles of African American (AA), Caucasian (Cau) and Caucasian Hispanic (H) patients at their first “induction naïve” LN flare

Methods

Kidney biopsies were done at the first episode of class III or IV LN in 13 AA, 11 Cau, and 8 H patients. Glomeruli were isolated by laser capture microdissection. RNA was analyzed using Nanostring technology. The expression of 579 genes was compared between groups. Transcripts with at least a 2-fold change and p <0.01 were considered differentially expressed

Results

Eight transcripts differentiated AA from Cau, one was upregulated. The expression of HLADRA was 2-fold higher and the immune-modulator HLADOB was 2-fold lower in AA compared to Cau. IL-4, a Th2 pathway gene was downregulated in AA compared to Cau. One hundred transcripts differentiated Cau from H. Thirty-three of these were upregulated in Cau compared to H. The top 3 upregulated transcripts were: fibronectin (FN1, fold change (FC) =34.82; p=1.8x10-12), osteopontin (SPP1, FC= 24.43; p=1.27x10-07) and FCER1G (FC 17.68; p=5.28x10-09). Pathway analysis revealed downregulation of INF (A1, A2 and B1) and Th2 signaling in Cau compared to H. Hundred and nine transcripts were downregulated in AA compared to H. The main pathways affected were T helper cell differentiation, Th1 and Th2 activation and T/B cell signaling.

Conclusion

Molecular signatures appear to be different for the same histologic class of LN in different races and ethnicities. The differences in HLA, IL4 and T/B cell signaling genes suggest a greater propensity toward immune activation and inflammation in AA compared to Cau. This may partly explain why AA LN patients have more severe kidney injury. The molecular signature of Cau compared to H suggests more inflammatory disease in Cau but more T cell-mediated immune activation in H

Funding

  • NIDDK Support