An exome-wide study of renal operational tolerance.
Homer2
IQCH
LCN2
NGAL
exome sequencing
operational tolerance
primary cilium
renal transplantation
Journal
Frontiers in medicine
ISSN: 2296-858X
Titre abrégé: Front Med (Lausanne)
Pays: Switzerland
ID NLM: 101648047
Informations de publication
Date de publication:
2022
2022
Historique:
received:
23
06
2022
accepted:
31
10
2022
medline:
2
6
2023
pubmed:
2
6
2023
entrez:
2
6
2023
Statut:
epublish
Résumé
Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients. We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples. We identified rare variants of Rare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444.
Sections du résumé
Background
UNASSIGNED
Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients.
Methods
UNASSIGNED
We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples.
Results
UNASSIGNED
We identified rare variants of
Conclusion
UNASSIGNED
Rare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444.
Identifiants
pubmed: 37265662
doi: 10.3389/fmed.2022.976248
pmc: PMC10230038
doi:
Banques de données
ClinicalTrials.gov
['NCT05124444']
Types de publication
Journal Article
Langues
eng
Pagination
976248Investigateurs
Maria Aguilar Rodríguez
(M)
Friederike Bachmann
(F)
Rajendra Bahadur Shahi
(RB)
Frederike Bemelman
(F)
Luboslav Bena
(L)
Luigi Biancone
(L)
Laura Braun
(L)
Klemens Budde
(K)
Alejandro Camargo-Salamanca
(A)
Katia Clemente
(K)
Hulya Colak
(H)
Adrian Covic
(A)
Jacques Degreve
(J)
Philippe Gatault
(P)
François Glowacki
(F)
Karine Hadaya
(K)
Marc Hazzan
(M)
Bénédicte Janbon
(B)
Christophe Legendre
(C)
Umberto Maggiore
(U)
Marius Miglinas
(M)
Anja Mühlfeld
(A)
Maarten Naesens
(M)
Christian Noël
(C)
Rainer Oberbauer
(R)
Evangeline Pillebout
(E)
Gian Benedetto Piredda
(GB)
Francesco Pisani
(F)
Ana Ramírez Puga
(AR)
Tomas Reischig
(T)
Francisco González-Roncero
(F)
Søren Schwartz Sørensen
(SS)
Daniel Seron Micas
(DS)
Nurhan Seyahi
(N)
Dimitrie Siriopol
(D)
Goce Spasovski
(G)
Jean-François Subra
(JF)
Erik Teugels
(E)
Serhan Tuǧlular
(S)
Sonia Van Dooren
(S)
Catheline Vilain
(C)
Florence Villemain
(F)
Xavier Warling
(X)
Bruno Watschinger
(B)
Laurent Weekers
(L)
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2023 Massart, Danger, Olsen, Emond, Viklicky, Jacquemin, Soblet, Duerinckx, Croes, Perazzolo, Hruba, Daneels, Caljon, Sever, Pascual, Miglinas, the Renal Tolerance Investigators, Pirson, Ghisdal, Smits, Giral, Abramowicz, Abramowicz and Brouard.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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