Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F23%3A10464980" target="_blank" >RIV/00064203:_____/23:10464980 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/23:10464980

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=yYMHEnbWcE" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=yYMHEnbWcE</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ajt.2023.06.003" target="_blank" >10.1016/j.ajt.2023.06.003</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies

Popis výsledku v původním jazyce

In lung transplantation, antibody-mediated rejection (AMR) diagnosed by ISHLT criteria is uncommon compared to other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often DSA-negative and associated with NK cell transcripts. We therefore searched for a similar molecular ABMR-like state in transbronchial biopsies (TBBs) using gene expression microarray results from the INTERLUNG study (#NCT02812290). After optimizing rejection-selective transcript sets (RSTS) in a training set (n = 488), the resulting algorithms separated an NK cell-enriched rejection-like state (NKRL) from TCMR/Mixed in a test set (n = 488). Applying this approach to all 896 TBBs distinguished three groups - No rejection; TCMR/Mixed; and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with CLAD, reduced FEV1, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

Název v anglickém jazyce

Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies

Popis výsledku anglicky

In lung transplantation, antibody-mediated rejection (AMR) diagnosed by ISHLT criteria is uncommon compared to other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often DSA-negative and associated with NK cell transcripts. We therefore searched for a similar molecular ABMR-like state in transbronchial biopsies (TBBs) using gene expression microarray results from the INTERLUNG study (#NCT02812290). After optimizing rejection-selective transcript sets (RSTS) in a training set (n = 488), the resulting algorithms separated an NK cell-enriched rejection-like state (NKRL) from TCMR/Mixed in a test set (n = 488). Applying this approach to all 896 TBBs distinguished three groups - No rejection; TCMR/Mixed; and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with CLAD, reduced FEV1, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30213 - Transplantation

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

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

1600-6143

Svazek periodika

23

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

1922-1938

Kód UT WoS článku

001165316200001

EID výsledku v databázi Scopus

2-s2.0-85162889615