Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

0 avis

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Archive ouverte

Edité par CCSD ; Nature Publishing Group -

International audience. Abstract 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.

Langue: en

Consulter en ligne

Consulter le document

Suggestions

Du même auteur

Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases

Archive ouverte | Barturen, Guillermo | CCSD

International audience. Clinical heterogeneity, a hallmark of systemic autoimmune diseases, impedes early diagnosis and effective treatment, issues that may be addressed if patients could be classified into groups d...

A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome. A new molecular classification to drive precision treatment strategies in primary Sjögren’s syndrome: Identification of altered cell signaling pathways using proteomic profiling in stable and progressive chronic lymphocytic leukemia.

Archive ouverte | Soret, Perrine | CCSD

International audience. Abstract There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- b...

An integrative multi-omics approach in Sjögren’s Syndrome identifies novel genetic drivers with regulatory function and disease-specificity

Archive ouverte | Teruel, María | CCSD

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 ...

Chargement des enrichissements...