IDO + Endothelial Cells in Glomeruli of Kidney Transplantation Patients With Glomerulitis.
Autor: | Hendriks SH; Department of Immunology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., Heidt S; Department of Immunology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands.; Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands., Krop J; Department of Immunology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., IJsselsteijn ME; Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., Eggermont J; Department of LKEB Radiology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., Kers J; Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Pathology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Reinders MEJ; Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Pathology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., Koning F; Department of Immunology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands., van Kooten C; Department of Internal Medicine (Nephrology) and Transplant Center, Leiden University Medical Center, Leiden University, Leiden, the Netherlands. |
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Jazyk: | angličtina |
Zdroj: | Transplantation direct [Transplant Direct] 2024 Jul 05; Vol. 10 (8), pp. e1674. Date of Electronic Publication: 2024 Jul 05 (Print Publication: 2024). |
DOI: | 10.1097/TXD.0000000000001674 |
Abstrakt: | Background: Kidney transplantation is the preferred treatment option for patients with end-stage renal disease. However, long-term graft survival remains a challenge. The enzyme indoleamine 2,3 dioxygenase (IDO) has been reported to have immunomodulatory effects with IDO transcripts being elevated in both antibody-mediated rejection and T cell-mediated rejection. Methods: A metal-conjugated antibody panel for the staining of kidney biopsies was developed, allowing the visualization of 41 structural and immune markers on a single tissue slide to gain in-depth insight into the composition and localization of the immune cell compartment. Staining was applied to week 4 and 24 protocol biopsies of 49 patients as well as on 15 indication biopsies of the TRITON study and 4 additional transplantation biopsies with glomerulitis. Results: A highly distinctive and specific glomerular IDO expression was observed in biopsies from 3 of 49 patients in imaging mass cytometry. Immunohistochemistry confirmed IDO expression in glomeruli of 10 of 10 cases with glomerulitis. IDO was found to be expressed by CD31 + glomerular endothelial cells, accompanied by the presence of granzyme-B + Tbet + CD7 + CD45RA + natural killer cells and CD68 + macrophages. Furthermore, a proportion of both the immune cells and endothelial cells expressed Ki-67, indicative of cell proliferation, which was not observed in control glomeruli. Conclusions: Our results show glomerular IDO expression in transplanted kidneys with glomerulitis, which is accompanied by increased numbers of natural killer cells and macrophages and likely reflects local immune activation. (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.) |
Databáze: | MEDLINE |
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