Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F15%3A00059562" target="_blank" >RIV/00023001:_____/15:00059562 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/15:10306868 RIV/00216208:11140/15:10306868 RIV/00064190:_____/15:#0001125 RIV/00023736:_____/15:00011382

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S215717161532267X" target="_blank" >http://www.sciencedirect.com/science/article/pii/S215717161532267X</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/ki.2015.211" target="_blank" >10.1038/ki.2015.211</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes

Popis výsledku v původním jazyce

The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity-and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Název v anglickém jazyce

Molecular diagnostics identifies risks for graft dysfunction despite borderline histologic changes

Popis výsledku anglicky

The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity-and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30213 - Transplantation

Projekt

<a href="/cs/project/7E13020" target="_blank" >7E13020: Personalized minimization of immunosuppression after solid organ transplantation by biomarker-driven stratification of patients to improve long-term outcome and health-economic data of transplantation</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Kidney international

ISSN

0085-2538

e-ISSN

—

Svazek periodika

88

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

785-795

Kód UT WoS článku

000362219600019

EID výsledku v databázi Scopus

2-s2.0-84942889787