PT  - JOURNAL ARTICLE
AU  - Bhairav Paleja
AU  - Andrea Low Hsiu Ling
AU  - Pavanish Kumar
AU  - Suzan Saidin
AU  - Ahmad Lajam
AU  - Sharifah Nur Hazirah
AU  - Camillus Chua
AU  - Lai Li Yun
AU  - Salvatore Albani
TI  - Systemic sclerosis is a disease of a prematurely senescent, inflammatory and activated immunome
AID  - 10.1101/637736
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 637736
4099  - http://biorxiv.org/content/early/2019/05/16/637736.short
4100  - http://biorxiv.org/content/early/2019/05/16/637736.full
AB  - Systemic sclerosis (SSc) is an autoimmune disease characterised by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets have been reported in SSc, however there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients and healthy controls (HC) were analysed by mass cytometry using a 36 marker (cell-surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and MAIT cells in patients, accompanied with increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation mediated “premature senescence” of immune cells.ONE SENTENCE SUMMARY The immune architecture in Systemic sclerosis is altered and reminiscent of chronic stimulatory environment led premature senescence of immune cells.