RT Journal Article
SR Electronic
T1 Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren’s syndrome
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1458
OP 1466
DO 10.1136/annrheumdis-2016-210788
VO 76
IS 8
A1 Shinya Tasaki
A1 Katsuya Suzuki
A1 Ayumi Nishikawa
A1 Yoshiaki Kassai
A1 Maiko Takiguchi
A1 Rina Kurisu
A1 Yuumi Okuzono
A1 Takahiro Miyazaki
A1 Masaru Takeshita
A1 Keiko Yoshimoto
A1 Hidekata Yasuoka
A1 Kunihiro Yamaoka
A1 Kazuhiro Ikeura
A1 Kazuyuki Tsunoda
A1 Rimpei Morita
A1 Akihiko Yoshimura
A1 Hiroyoshi Toyoshiba
A1 Tsutomu Takeuchi
YR 2017
UL http://ard.bmj.com/content/76/8/1458.abstract
AB Objectives Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren’s syndrome (SS) pathology.Methods We generated multiple data set from well-defined patients with SS, which includes whole-blood transcriptomes, serum proteomes and peripheral immunophenotyping. Based on our newly generated data, we performed an extensive bioinformatic investigation.Results Our integrative analysis identified SS gene signatures (SGS) dysregulated in widespread omics layers, including epigenomes, mRNAs and proteins. SGS predominantly involved the interferon signature and ADAMs substrates. Besides, SGS was significantly overlapped with SS-causing genes indicated by a genome-wide association study and expression trait loci analyses. Combining the molecular signatures with immunophenotypic profiles revealed that cytotoxic CD8 ­T cells­ were associated with SGS. Further, we observed the activation of SGS in cytotoxic CD8 T cells isolated from patients with SS.Conclusions Our multiomics investigation identified gene signatures deeply associated with SS pathology and showed the involvement of cytotoxic CD8 T cells. These integrative relations across multiple layers will facilitate our understanding of SS at the system level.