dc.contributor |
Universitat de Barcelona |
dc.contributor.author |
Sigdel, Tara K. |
dc.contributor.author |
Bestard Matamoros, Oriol |
dc.contributor.author |
Salomonis, Nathan |
dc.contributor.author |
Hsieh, Szu-Chuan |
dc.contributor.author |
Torras Ambròs, Joan |
dc.contributor.author |
Naesens, Maarten |
dc.contributor.author |
Tran, Tim Q. |
dc.contributor.author |
Roedder, Silke |
dc.contributor.author |
Sarwal, Minnie M. |
dc.date |
2019-03-12T11:16:56Z |
dc.date |
2019-03-12T11:16:56Z |
dc.date |
2016-10 |
dc.date |
2019-03-12T11:16:56Z |
dc.identifier.citation |
0041-1337 |
dc.identifier.citation |
665166 |
dc.identifier.uri |
http://hdl.handle.net/2445/130097 |
dc.format |
9 p. |
dc.format |
application/pdf |
dc.language.iso |
eng |
dc.publisher |
Lippincott, Williams & Wilkins |
dc.relation |
Versió postprint del document publicat a: https://doi.org/10.1097/TP.0000000000001214 |
dc.relation |
Transplantation, 2016, vol. 100, num. 10, p. 2062-2070 |
dc.relation |
https://doi.org/10.1097/TP.0000000000001214 |
dc.rights |
(c) Lippincott, Williams & Wilkins, 2016 |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Antígens |
dc.subject |
Genètica |
dc.subject |
Malalties del ronyó |
dc.subject |
Trasplantament renal |
dc.subject |
Efectes secundaris |
dc.subject |
Infeccions |
dc.subject |
Antigens |
dc.subject |
Genetics |
dc.subject |
Kidney diseases |
dc.subject |
Kidney transplantation |
dc.subject |
Side effects |
dc.subject |
Infections |
dc.title |
Intragraft antiviral-specific gene expression as a distinctive transcriptional signature for studies in polyomavirus-associated nephropathy |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/acceptedVersion |
dc.description.abstract |
Background: polyomavirus nephropathy (PVAN) is a common cause of kidney allograft dysfunction and loss. To identify PVAN-specific gene expression and underlying molecular mechanisms, we analyzed kidney biopsies with and without PVAN. Methods: the study included 168 posttransplant renal allograft biopsies (T cell-mediated rejection [TCMR] = 26, PVAN = 10, normal functioning graft = 73, and interstitial fibrosis/tubular atrophy = 59) from 168 unique kidney allograft recipients. We performed gene expression assays and bioinformatics analysis to identify a set of PVAN-specific genes. Validity and relevance of a subset of these genes are validated by quantitative polymerase chain reaction and immunohistochemistry. Results: unsupervised hierarchical clustering analysis of all the biopsies revealed high similarity between PVAN and TCMR gene expression. Increased statistical stringency identified 158 and 252 unique PVAN and TCMR injury-specific gene transcripts respectively. Although TCMR-specific genes were overwhelmingly involved in immune response costimulation and TCR signaling, PVAN-specific genes were mainly related to DNA replication process, RNA polymerase assembly, and pathogen recognition receptors. A principal component analysis (PCA) using these genes further confirmed the most optimal separation between the 3 different clinical phenotypes. Validation of 4 PVAN-specific genes (RPS15, complement factor D, lactotransferrin, and nitric oxide synthase interacting protein) by quantitative polymerase chain reaction and confirmation by immunohistochemistry of 2 PVAN-specific proteins with antiviral function (lactotransferrin and IFN-inducible transmembrane 1) was done. Conclusions: in conclusion, even though PVAN and TCMR kidney allografts share great similarities on gene perturbation, PVAN-specific genes were identified with well-known antiviral properties that provide tools for discerning PVAN and AR as well as attractive targets for rational drug design. |