Abstract: SA-PO104

Molecular Heterogeneity of the Kidney in Lupus Nephritis (LN) in Patients of Different Races and Ethnicities

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Ayoub, Isabelle, Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Rovin, Brad H., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico, Mexico
  • Birmingham, Daniel J., Ohio State University Wexner Medical Center, Columbus, Ohio, 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
  • 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
  • Satoskar, Anjali A., Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Yu, Lianbo, Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Group or Team Name

  • CKD Biomarker Consortium
Background

Black and Hispanic LN patients often have a more severe course and worse renal outcomes than white patients. This has been attributed to several factors, including socioeconomic status. We postulated that activation of different pathogenic pathways during LN may account, in part, for these racial/ethnic differences. To test this hypothesis the kidney transcriptomes of black, Hispanic and white patients were examined at LN flare.

Methods

Kidney biopsy was done at the first episode of LN in black (n=5), white (n=2) and Hispanic (n=3) SLE patients. All showed class III or IV LN. Glomeruli were isolated using laser capture microdissection. RNA was extracted and transcript expression analyzed by Nanostring technology. The expression of 358 immune/inflammatory genes was compared in blacks, whites and Hispanics

Results

As shown in the table, 3 transcripts were significantly upregulated and 3 transcripts were significantly decreased in glomeruli from black and Hispanic patients compared to glomeruli from white patients. Two transcripts were significantly upregulated in glomeruli from black and white patients compared to Hispanic patients (table)

Conclusion

Intra-renal molecular signatures appear to be different for the same histologic classes of LN among different races and ethnicities. The data suggest, for example, that interferonγ may be higher in black and Hispanic patients given the upregulation of SPP1 and CD276. In contrast, downregulation of the protective HLA-DRB1and HLA-DQA1 in black and Hispanic patients may predispose to more severe injury. Such differences may help explain why standard treatments appear to be less effective in black and Hispanic than white patients. Understanding these pathways may allow more targeted therapies for specific groups of patients and improve long-term kidney outcomes.

Table
GeneBlack vs WhiteHispanic vs WhiteBlack vs HispanicWhite vs Hispanic
SPP15.0-fold; p=0.026.3-fold; p=0.02--
CXCL124.3-fold; p=0.046.3-fold; p=0.02--
CD2762.0-fold; p=0.022.3-fold; p=0.02--
CD340.3-fold; p<0.030.3-fold; p=0.03--
HLA-DQA10.04-fold; p<0.050.04-fold; p<0.001--
HLA-DRB10.04-fold; p<0.0010.017-fold; p=0.02--
TNFSF12--2.3-fold; p=0.023.9-fold; p=0.006
NFATC1--2.0-fold; p=0.013.0-fold; p=0.01

Funding

  • NIDDK Support