Dataset Information

Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjogren's syndrome.

ABSTRACT: 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.

SUBMITTER: Tasaki S

PROVIDER: S-EPMC5738597 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.

Tasaki Shinya S Suzuki Katsuya K Nishikawa Ayumi A Kassai Yoshiaki Y Takiguchi Maiko M Kurisu Rina R Okuzono Yuumi Y Miyazaki Takahiro T Takeshita Masaru M Yoshimoto Keiko K Yasuoka Hidekata H Yamaoka Kunihiro K Ikeura Kazuhiro K Tsunoda Kazuyuki K Morita Rimpei R Yoshimura Akihiko A Toyoshiba Hiroyoshi H Takeuchi Tsutomu T

Annals of the rheumatic diseases 20170518 8

<h4>Objectives</h4>Multiomics study was conducted to elucidate the crucial molecular mechanisms of primary Sjögren's syndrome (SS) pathology.<h4>Methods</h4>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.<h4>Results</h4>Our integrative analysis identified SS gene signatures (SGS) dysregulated in w ...[more]

PMID: 28522454

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Project description:Sjögren's disease (SjD) is the second most prevalent autoimmune disorder that involves chronic inflammation of exocrine glands. Correct diagnosis of primary SjD (pSjD) can span over many years since disease symptoms manifest only in advanced stages of salivary and lachrymal glandular destruction, and consensus diagnostic methods have critical sensitivity and selectivity limitations. Using nuclear magnetic resonance (NMR) spectroscopy, we determined the composition of metabolites in unstimulated saliva samples from 30 pSjD subjects and 30 participants who do not have Sjögren's disease (non-Sjögren's control group, NS-C). Thirty-four metabolites were quantified in each sample, and analysis was conducted on both non-normalized (concentration) and normalized metabolomics data from all study participants (ages 23-78) and on an age-restricted subset of the data (ages 30-70) while applying false discovery rate correction in determining data significance. The normalized data of saliva samples from all study participants, and of the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate, as well as significant decreases in the levels of 5-aminopentanoate, acetate, butyrate and propionate, in subjects with pSjD compared to subjects in the NS-C group. Additionally, a significant increase in choline was found only in the age-restricted subset, and a significant decrease in fucose was found only in the whole study population in normalized data of saliva samples from the pSjD group compared to the NS-C group. Metabolite concentration data of saliva samples from all study participants, but not from the age-restricted subset, indicated significant increases in the levels of glucose, glycerol, taurine, and lactate in subjects with pSjD compared to controls. The study showed that NMR metabolomics can be implemented in defining salivary metabolic signatures that are associated with disease status, and can contribute to differential analysis between subjects with pSjD and those who are not affected with this disease, in the clinic.

Dataset Information

Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjogren's syndrome.

Publications

Multiomic disease signatures converge to cytotoxic CD8 T cells in primary Sjögren's syndrome.

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