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Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis

Authors :
Marie Hudson
Sasha Bernatsky
Ines Colmegna
Maximilien Lora
Tomi Pastinen
Kathleen Klein Oros
Celia M. T. Greenwood
Source :
Epigenetics, Vol 12, Iss 6, Pp 433-440 (2017)
Publication Year :
2017
Publisher :
Taylor & Francis Group, 2017.

Abstract

We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4+ T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases. We recruited 13 seropositive rheumatoid arthritis, 19 systemic sclerosis, 12 systemic lupus erythematosus subjects, and 8 healthy controls. We identified 33 genes that were both differentially methylated and expressed (26 over- and 7 under-expressed) in SARD cases versus controls. The most highly overexpressed gene was CD1C (log fold change in expression = 1.85, adjusted P value = 0.009). In functional analysis (Ingenuity Pathway Analysis), the top network identified was lipid metabolism, molecular transport, small molecule biochemistry. The top canonical pathways included the mitochondrial L-carnitine shuttle pathway (P = 5E-03) and PTEN signaling (P = 8E-03). The top upstream regulator was HNF4A (P = 3E-05). This novel SARD signature contributes to ongoing work to further our understanding of the molecular mechanisms underlying SARD and provides novel targets of interest.

Details

Language :
English
ISSN :
15592294 and 15592308
Volume :
12
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Epigenetics
Publication Type :
Academic Journal
Accession number :
edsdoj.3ca734fee29b46289d8f65ba5a219be9
Document Type :
article
Full Text :
https://doi.org/10.1080/15592294.2017.1303581