Back to Search
Start Over
Natural killer cell infiltration is discriminative for antibody-mediated rejection and predicts outcome after kidney transplantation.
- Source :
-
Kidney international [Kidney Int] 2019 Jan; Vol. 95 (1), pp. 188-198. Date of Electronic Publication: 2018 Nov 03. - Publication Year :
- 2019
-
Abstract
- Despite partial elucidation of the pathophysiology of antibody-mediated rejection (ABMR) after kidney transplantation, it remains largely unclear which of the involved immune cell types determine disease activity and outcome. We used microarray transcriptomic data from a case-control study (n=95) to identify genes that are differentially expressed in ABMR. Given the co-occurrence of ABMR and T-cell-mediated rejection (TCMR), we built a bioinformatics pipeline to distinguish ABMR-specific mRNA markers. Differential expression of 503 unique genes was identified in ABMR, with significant enrichment of natural killer (NK) cell pathways. CIBERSORT (Cell type Identification By Estimating Relative Subsets Of known RNA Transcripts) deconvolution analysis was performed to elucidate the corresponding cell subtypes and showed increased NK cell infiltration in ABMR in comparison to TCMR and normal biopsies. Other leukocyte types (including monocytes/macrophages, CD4 and CD8 T cells, and dendritic cells) were increased in rejection, but could not discriminate ABMR from TCMR. Deconvolution-based estimation of NK cell infiltration was validated using computerized morphometry, and specifically associated with glomerulitis and peritubular capillaritis. In an external data set of kidney transplant biopsies, activated NK cell infiltration best predicted graft failure amongst all immune cell subtypes and even outperformed a histologic diagnosis of acute rejection. These data suggest that NK cells play a central role in the pathophysiology of ABMR and graft failure after kidney transplantation.<br /> (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Allografts cytology
Allografts immunology
Allografts pathology
Biomarkers analysis
Biopsy
Case-Control Studies
Computational Biology
Datasets as Topic
Female
Gene Expression Profiling
Graft Rejection genetics
Graft Rejection immunology
Graft Rejection pathology
Humans
Kidney cytology
Kidney immunology
Kidney pathology
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Prognosis
Treatment Outcome
Young Adult
Antibodies immunology
Graft Rejection diagnosis
Kidney Failure, Chronic surgery
Kidney Transplantation adverse effects
Killer Cells, Natural immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 95
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 30396694
- Full Text :
- https://doi.org/10.1016/j.kint.2018.08.027