Biomarkers of tolerance in kidney transplantation: Are we predicting tolerance or response to immunosuppressive treatment?

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F16%3A00060108" target="_blank" >RIV/00023001:_____/16:00060108 - isvavai.cz</a>

Výsledek na webu

<a href="http://onlinelibrary.wiley.com/doi/10.1111/ajt.13932/epdf" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/ajt.13932/epdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/ajt.13932" target="_blank" >10.1111/ajt.13932</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Biomarkers of tolerance in kidney transplantation: Are we predicting tolerance or response to immunosuppressive treatment?

Popis výsledku v původním jazyce

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Název v anglickém jazyce

Biomarkers of tolerance in kidney transplantation: Are we predicting tolerance or response to immunosuppressive treatment?

Popis výsledku anglicky

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FE - Ostatní obory vnitřního lékařství

OECD FORD obor

—

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

American journal of transplantation

ISSN

1600-6135

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

3443-3457

Kód UT WoS článku

000388208600016

EID výsledku v databázi Scopus

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