Autoimmune rheumatologic diseases
We have created a high dimensionality atlas of the healthy human immunome (EPIC: Extended Poly-dimensional Immunome Characterization) by interrogating PBMC of 200+ healthy subjects with 63 unique mechanistic and phenotypic markers byCytof. EPIC provides a detailed depiction of the architecture of the human healthy Immunome. We tested here the hypothesis that eRA as a whole pathological process can be studied as a perturbation of the healthy immunome, thus allowing the identification of pathways and cell subsets, and their overall organization, in a way that is mechanistically and clinically poignant.
We tested eRA patients at diagnosis, with active disease and before establishing therapy, using the EPIC panels and analysis tools and compared the resulting Immunome architecture against the healthy EPIC atlas. Dimensionality reduction and clustering were used to group the cells into subsets. Correlation-based Immune cell networks were created to depict and dissect the immunome of both groups<./p>
System level analysis of immune cell network showed a decrease in regulatory cellular networks in eRA. Also, the eRA immune cell network showed higher modularity and centralization when compared to healthy network, suggesting the emergence of specific functions dominated by few subsets, mainly of inflammatory, experienced adaptive nature, all related to each other. This approach enables the identification of relevant individual immune subsets and underscores the functional relations of all subsets organised within an architecture which profoundly differs from normal. This knowledge can be exploited to understand pathogenesis and also understand and predict effects of disease activity or therapy.