Relating molecular T cell-mediated rejection activity in kidney transplant biopsies to time and to histologic tubulitis and atrophy-fibrosis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F23%3A00083945" target="_blank" >RIV/00023001:_____/23:00083945 - isvavai.cz</a>

Výsledek na webu

<a href="https://journals.lww.com/transplantjournal/Fulltext/2023/05000/Relating_Molecular_T_Cell_mediated_Rejection.17.aspx" target="_blank" >https://journals.lww.com/transplantjournal/Fulltext/2023/05000/Relating_Molecular_T_Cell_mediated_Rejection.17.aspx</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1097/TP.0000000000004396" target="_blank" >10.1097/TP.0000000000004396</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Relating molecular T cell-mediated rejection activity in kidney transplant biopsies to time and to histologic tubulitis and atrophy-fibrosis

Popis výsledku v původním jazyce

Background. We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant.Methods. We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study ( #NCT01299168). TCMR activity was defined by a molecular classifier.Results. Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection (&quot;mixed&quot;) activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity.Conclusions. TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.

Název v anglickém jazyce

Relating molecular T cell-mediated rejection activity in kidney transplant biopsies to time and to histologic tubulitis and atrophy-fibrosis

Popis výsledku anglicky

Background. We studied the variation in molecular T cell-mediated rejection (TCMR) activity in kidney transplant indication biopsies and its relationship with histologic lesions (particularly tubulitis and atrophy-fibrosis) and time posttransplant.Methods. We examined 175 kidney transplant biopsies with molecular TCMR as defined by archetypal analysis in the INTERCOMEX study ( #NCT01299168). TCMR activity was defined by a molecular classifier.Results. Archetypal analysis identified 2 TCMR classes, TCMR1 and TCMR2: TCMR1 had higher TCMR activity and more antibody-mediated rejection (&quot;mixed&quot;) activity and arteritis but little hyalinosis, whereas TCMR2 had less TCMR activity but more atrophy-fibrosis. TCMR1 and TCMR2 had similar levels of molecular injury and tubulitis. Both TCMR1 and TCMR2 biopsies were uncommon after 2 y posttransplant and were rare after 10 y, particularly TCMR1. Within late TCMR biopsies, TCMR classifier activity and activity molecules such as IFNG fell progressively with time, but tubulitis and molecular injury were sustained. Atrophy-fibrosis was increased in TCMR biopsies, even in the first year posttransplant, and rose with time posttransplant. TCMR1 and TCMR2 both reduced graft survival, but in random forests, the strongest determinant of survival after biopsies with TCMR was molecular injury, not TCMR activity.Conclusions. TCMR varies in intensity but is always strongly related to molecular injury and atrophy-fibrosis, which ultimately explains its effect on survival. We hypothesize, based on the reciprocal relationship with hyalinosis, that the TCMR1-TCMR2 gradient reflects calcineurin inhibitor drug underexposure, whereas the time-dependent decline in TCMR activity and frequency after the first year reflects T-cell exhaustion.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30217 - Urology and nephrology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Transplantation

ISSN

0041-1337

e-ISSN

1534-6080

Svazek periodika

107

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

1102-1114

Kód UT WoS článku

000978303100022

EID výsledku v databázi Scopus

2-s2.0-85153900423