The Innate Immune-System May Play an Enhanced Role in Acute Cellular Rejection in Patients on Belatacept-Based Immunosuppression.
1Department of Pathology, University of California, San Francisco, San Francisco, CA
2Department of Surgery, Division of Transplant Surgery, University of California, San Francisco, San Francisco, CA
3Department of Medicine, Division of Nephrology, University of California, San Francisco, San Francisco, CA
Meeting: 2017 American Transplant Congress
Abstract number: 136
Session Information
Session Name: Concurrent Session: Kidney: Acute Cellular Rejection
Session Type: Concurrent Session
Date: Sunday, April 30, 2017
Session Time: 4:30pm-6:00pm
Presentation Time: 5:30pm-5:42pm
Location: E451b
Purpose. The incidence of acute cellular rejection (ACR) in kidney transplant patients on Belatacept (Bela-ACR) is higher than in those with CNI-based regimens (CNI-ACR). However, the pathogenetic mechanisms of Bela-ACR are poorly understood. To explore the potential underlying mechanisms of Bela-ACR, gene expression profiles of Bela-ACR were compared with CNI-ACR in transplant kidney biopsies.
Methods. Patients with a biopsy diagnosis of ACR on Belatacept (n=12) or CNI-based regimen (n=12) were enrolled into the study. Six month protocol biopsies with no pathologic changes served as controls (n=12). Gene expression analysis was performed on formalin-fixed paraffin-embedded tissues with the NanoString nCounter platform using a customized panel of 800 genes. Multivariate regression analysis was carried out to compare log2-transformed gene-expression levels of ACR, Bela-ACR, and control groups.
Results. The great majority of the known cellular rejection-associated molecular pathways were upregulated in both Bela-ACR and CNI-ACR. However, genes related to pathogen-associated molecular pattern recognition pathways, NK cell function, IDO-1 and other members of the innate immune-system regulatory network were significantly overexpressed in the Bela-ACR group compared to CNI-ACR cases (selected examples are shown in Table 1).
| mRNA | Log2 fold change | Lower confidence limit | Upper confidence limit | corrected p-value |
| TLR4 | 0.605 | 0.299 | 0.91 | 0.0385 |
| FcɣIIIR | 1.32 | 0.622 | 2.02 | 0.0402 |
| IDO-1 | 1.66 | 0.829 | 2.5 | 0.0385 |
Conclusions. Although there is significant overlap in the gene expression profiles between Bela-ACR and CNI-ACR, the innate immune system gene expression-footprint of Bela-ACR is distinctly different from that of CNI-ACR. While the overexpression of activating genes may indicate enhanced engagement of NK and other innate immune cells in Bela-ACR, upregulation of the regulatory genes may suggest the inefficacy of innate regulatory mechanisms in controlling cellular alloimmunity.
CITATION INFORMATION: Dobi D, Tang Q, Chandran S, Vincenti F, Laszik Z. The Innate Immune-System May Play an Enhanced Role in Acute Cellular Rejection in Patients on Belatacept-Based Immunosuppression. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Dobi D, Tang Q, Chandran S, Vincenti F, Laszik Z. The Innate Immune-System May Play an Enhanced Role in Acute Cellular Rejection in Patients on Belatacept-Based Immunosuppression. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/the-innate-immune-system-may-play-an-enhanced-role-in-acute-cellular-rejection-in-patients-on-belatacept-based-immunosuppression/. Accessed November 25, 2024.« Back to 2017 American Transplant Congress