Immune Cell Infiltration is Discriminative for ABMR and TCMR

Author:

Zheng Bingxuan1,Dou Meng1,Deng Ge1,Wei Tian1,Niu Zejiaxin1,Ding Chenguang1,Xue Wujun1,Tian Puxun1

Affiliation:

1. Department of Kidney Transplantation, The First Affiliated Hospital of Xi’an Jiaotong University

Abstract

Abstract Antibody-mediated rejection (ABMR) and T cell-mediated rejection (TCMR) are the important causes of kidney transplant failure. Here, we aimed to evaluate the different levels and composition of infiltrating immune cells in kidney allografts of patients with ABMR or TCMR. Gene expression profiles GSE36059 and GSE48581 were obtained from the GEO database. Then, an established algorithm method called CIBERSORT was used to estimate the abundance of 22 immune cells based on microarray profiles in the GSE36059 dataset. The GSE48581 dataset was used as a validation cohort to confirm the different infiltrating immune cells between the ABMR and the TCMR groups. Receiver operating characteristic (ROC) curve analysis was used to assess the value of the infiltrating immune cells in discriminating ABMR from TCMR. Immune infiltration analysis by CIBERSORT method showed that TCMR samples had a higher level of T cell subsets compared with the ABMR samples. In the TCMR group, a significant increase in CD4 + activated memory T cells, follicular helper T cells, gamma delta (GD) T cells was observed. In the ABMR group, we found that plasma cells, resting NK cells, activated NK cells, and resting dendritic cells were increased. Similar results were also obtained in the validation cohort. The combined analysis of these infiltrating immune cells in discriminating ABMR from TCMR had an AUC of 0.839 (95% CI: 0.753–0.924) in the GSE36059 dataset and an AUC of 0.899 (95% CI: 0.823–0.975) in the validation cohort. Our data suggest that there was an obvious difference in immune infiltration between ABMR and TCMR. Plasma cells, resting NK cells, activated NK cells, resting dendritic cells, CD4 + activated memory T cells, follicular helper T cells combined with gamma delta T cells could better discriminate ABMR from TCMR.

Publisher

Research Square Platform LLC

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