Differentially Expressed IL-6Rα and GP130 Genes in Kidney Biopsies (Bxs) Suggests Different Roles of IL-6 Signaling in Antibody (ABMR)- and Cell (CMR)-Mediated Rejection
1Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles, CA
2Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Meeting: 2015 American Transplant Congress
Abstract number: C259
Keywords: Alloantibodies, Biopsy, Gene expression, Rejection
Session Information
Session Name: Poster Session C: Translational Biomarkers and Immune Monitoring
Session Type: Poster Session
Date: Monday, May 4, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background: IL-6 exerts immunoregulatory properties through IL-6 receptors, IL-6Rα and gp130. Our previous studies suggested the involvement of antibody-dependent cellular cytotoxicity (ADCC) and its related cytokines, IFNγ, IL-6 and TNFα in ABMR. We also found ADCC-related genes overexpressed in kidney Bxs with ABMR. Recently we reported higher expression of IL-6 and IL-6Rα in ABMR compared to CMR or control Bxs using immunohistochemistry. Further analysis of these Bxs was performed to examine IL-6, IL-6Rα, gp130 and other ADCC-related gene expression to investigate the involvement of IL-6 signaling in ABMR.
Methods:Total RNA was extracted from 34 Bxs (10 ABMR, 13 CMR, 11 Control without rejection) for reverse transcription-qPCR. The results were presented as fold change against a reference sample after normalized by a housekeeping gene, GAPDH. Comparisons were made among ABMR, CMR and control Bxs.
Results: Gene expression levels are summarized in the Table. IL-6 mRNA was not detected in most Bxs, suggesting extremely low expression levels. IL-6Rα gene expression was significantly higher in ABMR and CMR than control Bxs while no significant difference was seen between ABMR and CMR. In contrast, gp130 gene expression was significantly lower in CMR than ABMR and controls. Meanwhile, IFNγ, TNFα and other ADCC-related gene expression were elevated in ABMR compared to CMR and controls.
| Fold Change against a Reference Sample | ||||||||
| Genes | AMR | p: vs. Control | CMR | p: vs. Control | Controls | p: AMR vs. CMR | ||
| IL-6 | 0.03±0.05 | 0.23 | 0.25±0.48 | 0.28 | 0.00±0.00 | 0.20 | ||
| IL-6α | 1.6±0.9 | <0.01 | 1.6±1.5 | <0.05 | 0.1±0.1 | 0.96 | ||
| gp130 | 23±12 | 0.74 | 13±4 | <0.03 | 21±9 | <0.03 | ||
| IFNγ | 0.30±0.28 | <0.05 | 0.12±0.16 | 0.11 | 0.01±0.00 | 0.08 | ||
| TNFα | 0.40±0.29 | <0.01 | 0.20±0.25 | 0.06 | 0.01±0.02 | 0.09 | ||
| CCL3 | 0.07±0.10 | 0.08 | 0.02±0.02 | <0.05 | 0.00±0.00 | 0.12 | ||
| CD160 | 14±19 | 0.05 | 8±16 | 0.17 | 0.0±0.0 | 0.42 | ||
| CRTAM | 1.3±1.4 | <0.03 | 0.9±1.3 | 0.05 | 0.0±0.0 | 0.58 | ||
Conclusions: Higher expression of IL-6Rα, gp130 and other ADCC-related genes was seen in ABMR compared to CMR and control Bxs, suggesting involvement of IL-6 signaling, possibly induced by ADCC, in mediating ABMR. Since IL-6 signaling is also critical for B cell/plasma cell development as well as Th17 induction, interruption of IL-6/IL-6Rα/gp130 signaling may have utility for prevention and treatment of ABMR and CMR.
To cite this abstract in AMA style:
Zhang H, Thomas D, Kowalewska J, Suviolahti E, Shafi H, Nast C, Gertych A, Vo A, Haas M, Jordan S, Toyoda M. Differentially Expressed IL-6Rα and GP130 Genes in Kidney Biopsies (Bxs) Suggests Different Roles of IL-6 Signaling in Antibody (ABMR)- and Cell (CMR)-Mediated Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/differentially-expressed-il-6r-and-gp130-genes-in-kidney-biopsies-bxs-suggests-different-roles-of-il-6-signaling-in-antibody-abmr-and-cell-cmr-mediated-rejection/. Accessed November 21, 2024.« Back to 2015 American Transplant Congress