Autoimmune rheumatologic diseases
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 ought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients and its impact on disease severity and progression. Mononuclear cells from blood of SSc patients (n=20) and healthy controls (n=10) 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 systemic immunome in SSc, highlighting role of inflammation and chronic stimulation mediated “premature senescence” of immune cells, with implications to delineate mechanism of pathogenesis and identify diagnostic/therapeutic targets.