PT  - JOURNAL ARTICLE
AU  - Shinya Tasaki
AU  - Katsuya Suzuki
AU  - Ayumi Nishikawa
AU  - Yoshiaki Kassai
AU  - Maiko Takiguchi
AU  - Rina Kurisu
AU  - Yuumi Okuzono
AU  - Takahiro Miyazaki
AU  - Masaru Takeshita
AU  - Keiko Yoshimoto
AU  - Hidekata Yasuoka
AU  - Kunihiro Yamaoka
AU  - Kazuhiro Ikeura
AU  - Kazuyuki Tsunoda
AU  - Rimpei Morita
AU  - Akihiko Yoshimura
AU  - Hiroyoshi Toyoshiba
AU  - Tsutomu Takeuchi
TI  - Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren’s syndrome
AID  - 10.1136/annrheumdis-2016-210788
DP  - 2017 Aug 01
TA  - Annals of the Rheumatic Diseases
PG  - 1458--1466
VI  - 76
IP  - 8
4099  - http://ard.bmj.com/content/76/8/1458.short
4100  - http://ard.bmj.com/content/76/8/1458.full
SO  - Ann Rheum Dis2017 Aug 01; 76
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.