IDO + Endothelial Cells in Glomeruli of Kidney Transplantation Patients With Glomerulitis

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 antib...

Full description

Saved in:
Bibliographic Details
Published in:Transplantation direct 2024-08, Vol.10 (8), p.e1674
Main Authors: Hendriks, Sanne H, Heidt, Sebastiaan, Krop, Juliette, IJsselsteijn, Marieke E, Eggermont, Jeroen, Kers, Jesper, Reinders, Marlies E J, Koning, Frits, van Kooten, Cees
Format: Article
Language:English
Subjects:
Kidney Transplantation
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:2373-8731
2373-8731
DOI:10.1097/TXD.0000000000001674