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Abstract: TH-PO1055

Spatialomic Evaluation of Kidney Allograft Biopsies Reveals Distinct Glomerular and Nonglomerular Cortex Molecular and Cellular Profiles in T-Cell-Mediated Rejection and Antibody-Mediated Rejection (ABMR)

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Dorr, Casey R., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Rao, Zexi, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Guan, Weihua, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Grande, Joseph P., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Onyeaghala, Guillaume Chinedu, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Schladt, David P., Hennepin Healthcare Research Institute, Minneapolis, Minnesota, United States
  • Mohamed, Moataz, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Khan, Kohinoor, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Saqr, Abdelrahman, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Hudson, Erin E., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Barthel, Grant M., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Vo, Duy, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Gupta, Kajal, The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
  • Oetting, William S., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Bayat, Mahdi, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Klomjit, Nattawat, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Ding, Yanli, University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Mannon, Roslyn B., University of Nebraska Medical Center, Omaha, Nebraska, United States
  • Maltzman, Jonathan S., Stanford Medicine, Palo Alto, California, United States
  • Agarwal, Gaurav, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Jacobson, Pamala A., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Matas, Arthur J., University of Minnesota Twin Cities, Minneapolis, Minnesota, United States
  • Israni, Ajay K., The University of Texas Medical Branch at Galveston, Galveston, Texas, United States
Background

We hypothesized that macrophages, and differential transcriptional profiles, are associated with T-cell mediated acute rejection (TCMR) and antibody mediated acute rejection (ABMR) in kidney allograft biopsies and have differential abundance in the glomerular (Glom) or non-glomerular (nonGlom) cortex regions of interest (ROIs).

Methods

Kidney biopsies for acute kidney injury were grouped by local clinician’s biopsy finding as: without abnormalities (WA), TCMR or ABMR. Biopsies were profiled by Bruker GeoMx Whole Transcriptome Atlas (~18,000 transcripts); Glom or nonGlom cortex ROIs were pathologist-selected (Figure 1). Differentially expressed genes (DEGs) were identified by generalized estimating equations (GEEs), accounting for multiple ROIs per biopsy (Table 1). Cell proportions were estimated by SpatialDecon in R with Human Cell Atlas Kidney reference. P-values were false discovery rate (FDR) adjusted (Table 2).

Results

Compared with the WA group, spatialomics revealed that ABMR had more DEGs in Glom while TCMR had more DEGs in nonGlom (Table 1). Compared with WA, TCMR had more different cell types in nonGlom, while ABMR had more in the glom (Table 2). Tissue macrophages had strong association with both TCMR and ABMR compared to the WA in nonGlom (p.adj<0.0001) and in glom (p.adj<0.01).

Conclusion

Spatialomics may distinguish TCMR from ABMR via compartment-specific molecular and cellular signals.

Acknowledgment

R21AI171826 (Dorr), UMN CTSI K to R01 grant from 1UM1TR004405 (Dorr), 5U01AI058013 (Matas), U19AI070119 (Matas), K01AI130409 (Dorr)

Funding

  • Other NIH Support