The IL6/Th17 Pathway May Play Different Roles in Cell-Mediated and Antibody-Mediated Alloimmune Injury in Renal Allografts.
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: D125
Session Information
Session Name: Poster Session D: Kidney: Acute Cellular Rejection
Session Type: Poster Session
Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Purpose. IL6 has been shown to contribute to shifting the balance between tolerogenic regulatory T cells and proinflammatory Th17 cells towards the latter. Our study explores the differences between the expression patterns of IL6 (a master initiator of Th17 differentiation) and other Th17 signature genes across the Banff diagnostic categories of Normal, Borderline changes (BL), Acute cellular rejection (ACR), and Acute Antibody-mediated rejection (aAMR).
Material and Methods. 12 patients were enrolled from each diagnostic group. 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 BL, ACR, and aAMR groups to the baseline of Normal. Cell abundance scores were created by using the average of log2 transformed expression levels of genes specific to a given cell-type.
Results. While ACR and aAMR cases showed increased expression of IL6 compared to Normal cases (Table 1), BL group did not. Gene expression level of IL17-F was increased significantly only in aAMR compared to Normal (Table 1).
| mRNA | Log2 fold change | Lower confidence limit | Upper confidence limit | corrected p-value |
| IL6 (aAMR vs. Normal) | 2.48 | 1.51 | 3.44 | <0.0005 |
| IL6 (ACR vs. Normal) | 2.00 | 1.06 | 2.94 | <0.0005 |
| IL17-F (aAMR vs. Normal) | 1.09 | 0.477 | 1.71 | 0.0021 |
Th17 abundance score (Th17AS) was significantly different amongst different diagnostic groups (p<0.0005). Th17AS increased from the Normal group (4.37±0.38) to the BL (4.83±0.57), aAMR (5.98±0.54), and ACR (6.08±0.71) groups.
Conclusions. While signature genes reveal activation of the IL6/Th17 axis in both ACR and aAMR, only aAMR cases showed increased expression of IL17-F, one of the hallmark cytokines of the Th17 lineage. This may indicate a different role of IL6/Th17 pathway in aAMR relative to ACR. Biologic heterogeneity within the BL group might account for the lack of statistical separation of this group from the Normal cases.
CITATION INFORMATION: Dobi D, Tang Q, Chandran S, Vincenti F, Laszik Z. The IL6/Th17 Pathway May Play Different Roles in Cell-Mediated and Antibody-Mediated Alloimmune Injury in Renal Allografts. 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 IL6/Th17 Pathway May Play Different Roles in Cell-Mediated and Antibody-Mediated Alloimmune Injury in Renal Allografts. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/the-il6th17-pathway-may-play-different-roles-in-cell-mediated-and-antibody-mediated-alloimmune-injury-in-renal-allografts/. Accessed November 25, 2024.« Back to 2017 American Transplant Congress