Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 12 2021
02 12 2021
Historique:
received:
13
01
2021
accepted:
19
10
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
28
1
2022
Statut:
epublish
Résumé
Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population.
Identifiants
pubmed: 34857786
doi: 10.1038/s41598-021-01324-0
pii: 10.1038/s41598-021-01324-0
pmc: PMC8640069
doi:
Substances chimiques
Autoantibodies
0
HLA Antigens
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23292Investigateurs
Lorenzo Beretta
(L)
Barbara Vigone
(B)
Jacques-Olivier Pers
(JO)
Alain Saraux
(A)
Valérie Devauchelle-Pensec
(V)
Divi Cornec
(D)
Sandrine Jousse-Joulin
(S)
Bernard Lauwerys
(B)
Julie Ducreux
(J)
Anne-Lise Maudoux
(AL)
Carlos Vasconcelos
(C)
Ana Tavares
(A)
Esmeralda Neves
(E)
Raquel Faria
(R)
Mariana Brandão
(M)
Ana Campar
(A)
António Marinho
(A)
Fátima Farinha
(F)
Isabel Almeida
(I)
Miguel Angel Gonzalez-Gay Mantecón
(MAG)
Ricardo Blanco Alonso
(RB)
Alfonso Corrales Martínez
(AC)
Ricard Cervera
(R)
Ignasi Rodríguez-Pintó
(I)
Gerard Espinosa
(G)
Rik Lories
(R)
Ellen De Langhe
(E)
Nicolas Hunzelmann
(N)
Doreen Belz
(D)
Torsten Witte
(T)
Niklas Baerlecken
(N)
Georg Stummvoll
(G)
Michael Zauner
(M)
Michaela Lehner
(M)
Eduardo Collantes
(E)
Rafaela Ortega-Castro
(R)
Mª Angeles Aguirre-Zamorano
(MA)
Alejandro Escudero-Contreras
(A)
Mª Carmen Castro-Villegas
(MC)
Norberto Ortego
(N)
María Concepción Fernández Roldán
(MCF)
Enrique Raya
(E)
Inmaculada Jiménez Moleón
(IJ)
Enrique de Ramon
(E)
Isabel Díaz Quintero
(ID)
Pier Luigi Meroni
(PL)
Maria Gerosa
(M)
Tommaso Schioppo
(T)
Carolina Artusi
(C)
Carlo Chizzolini
(C)
Aleksandra Zuber
(A)
Donatienne Wynar
(D)
Laszló Kovács
(L)
Attila Balog
(A)
Magdolna Deák
(M)
Márta Bocskai
(M)
Sonja Dulic
(S)
Gabriella Kádár
(G)
Falk Hiepe
(F)
Velia Gerl
(V)
Silvia Thiel
(S)
Manuel Rodriguez Maresca
(MR)
Antonio López-Berrio
(A)
Rocío Aguilar-Quesada
(R)
Héctor Navarro-Linares
(H)
Montserrat Alvarez
(M)
Damiana Alvarez-Errico
(D)
Nancy Azevedo
(N)
Nuria Barbarroja
(N)
Anne Buttgereit
(A)
Qingyu Cheng
(Q)
Carlo Chizzolini
(C)
Jonathan Cremer
(J)
Aurélie De Groof
(A)
Ellen De Langhe
(E)
Julie Ducreux
(J)
Aleksandra Dufour
(A)
Velia Gerl
(V)
Maria Hernandez-Fuentes
(M)
Laleh Khodadadi
(L)
Katja Kniesch
(K)
Tianlu Li
(T)
Chary Lopez-Pedrera
(C)
Zuzanna Makowska
(Z)
Concepción Marañón
(C)
Brian Muchmore
(B)
Esmeralda Neves
(E)
Bénédicte Rouvière
(B)
Quentin Simon
(Q)
Elena Trombetta
(E)
Nieves Varela
(N)
Torsten Witte
(T)
Informations de copyright
© 2021. The Author(s).
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