TY - JOUR 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 SP - 1458 LP - 1466 DO - 10.1136/annrheumdis-2016-210788 VL - 76 IS - 8 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 Y1 - 2017/08/01 UR - http://ard.bmj.com/content/76/8/1458.abstract N2 - 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. ER -