Analysis of Immune Cell Proportions in Kidney Transplant Biopsies of Acute Cellular Rejection and Antibody Mediated Rejection Compared with Non-Rejecters

C. R. Dorr¹, A. Muthusamy¹, D. P. Schladt¹, W. Guan², B. Wu², J. S. Maltzman³, W. S. Oetting², P. A. Jacobson², A. K. Israni¹

¹Hennepin Healthcare Research Institute, Minneapolis, MN, ²University of Minnesota, Minneapolis, MN, ³Stanford University, Palo Alto, CA

Meeting: 2019 American Transplant Congress

Abstract number: A6

Keywords: Biopsy, Immunogenicity, Kidney transplantation, Rejection

Session Information

Session Name: Poster Session A: Acute Rejection

Session Type: Poster Session

Date: Saturday, June 1, 2019

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: Understanding the immune cell types that are associated with acute rejection (AR) in kidney transplant biopsies may lead to new therapeutic targets for AR. We investigated published microarray data to decipher the immune cell types in non-rejecters (NR) vs the AR subtypes acute cellular rejection (ACR) and antibody mediated rejection (AMR).

*Methods: We used Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) to enumerate immune cell-type abundance in biopsy samples from RNA transcript expression data. Normalized microarray data for the biopsy samples were from GEO database from studies GSE36059 (AMR, N=52; ACR, N=34; NR, N=165) and GSE48581 (AMR, N=35; ACR, N=29; NR, N=132). The relative proportion of 22 immune sub-types was predicted using CIBERSORT for biopsies that were categorized as NR, ACR or AMR. Additionally, we performed 4 separate logistic regression models and tested the global null hypothesis to determine differences between NR, ACR or AMR in each of the data sets.

*Results: The average immune subset fractions of 22 cell types in NR, ACR or AMR from two studies are shown in Figure 1. The differences of immune cell type distribution between NR, ACR or AMR are significant. For GSE36059: ACR vs. NR (p-value<0.0001) and AMR vs. NR (p-value<0.0001). For GSE48581: ACR vs. NR (p-value<0.0001) and AMR vs. NR (p-value=0.0027). For example, compared with NR, the ratio of M1/M2 macrophages in ACR and AMR is higher in both studies. For GSE36059: M1/M2 ratio in NR = 0.83, ACR = 1.04, AMR = 1.09. For GSE48581: M1/M2 ratio in NR = 0.57, ACR = 0.72, AMR = 0.72.

*Conclusions: Cell type proportions estimated from RNA expression data in kidney transplant biopsies are deferentially distributed between NR and ACR or AMR.

To cite this abstract in AMA style:

Dorr CR, Muthusamy A, Schladt DP, Guan W, Wu B, Maltzman JS, Oetting WS, Jacobson PA, Israni AK. Analysis of Immune Cell Proportions in Kidney Transplant Biopsies of Acute Cellular Rejection and Antibody Mediated Rejection Compared with Non-Rejecters [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/analysis-of-immune-cell-proportions-in-kidney-transplant-biopsies-of-acute-cellular-rejection-and-antibody-mediated-rejection-compared-with-non-rejecters/. Accessed November 22, 2024.

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