Th108 - The Integrated Cellular and Molecular Landscape of Autoimmunity

Pier Federico Gherardini – University of Rome "Tor Vergata"; Francesco Vallania – Immunologic; Manuela Helmer-Citterich – University of Rome "Tor Vergata"; Gerardo Pepe – University of Rome "Tor Vergata"

Abstract Text: Autoimmune disorders are a heterogeneous class of diseases affecting 5 to 10% of the global population and characterized by an aberrant immune response against healthy tissues and organs. Presently, treatment options aim to control disease by inducing systemic immuno-suppression, resulting in severe side-effects. Despite progress towards understanding risk factors and pathophysiology, current therapies are limited by an incomplete picture of the mechanism of disease due to their heterogeneity, both at a disease and patient level. A comparative analysis across different patient cohorts and diseases to reveal shared and distinct associated immune pathways is currently missing.
Here, we present a molecular and cellular landscape describing 11 autoimmune diseases generated by analyzing and integrating 13,054 publicly available transcriptomes of whole blood and tissue biopsies across 182 datasets. For each gene expression sample, we computationally inferred cellular composition of circulating immune cells and infiltrates (n = 20), cytokine levels (n = 275), pathway (n = 582), transcription factor (n = 727) and microRNA activity scores (n = 740). We then employed meta-analysis to integrate these biologically relevant features across all datasets separately between tissue and blood-derived samples, identifying regulatory modules that are unique and shared across diseases while minimizing the effect of cohort-specific confounders. Our ongoing work provides a foundational analysis and contributes towards the understanding of the molecular mechanisms across autoimmunity.