AutoCore: network-based definition of the core module of human autoimmunity and autoinflammation

Although research on rare autoimmune and autoinflammatory diseases has
enabled definition of non-redundant regulators of homeostasis in human
immunity, due to the single gene-single disease nature of many of these
diseases, contributing factors were mostly unveiled in sequential and
non-coordinated individual studies. Here, we used a network-based approach
for integrating a set of 186 inborn errors of immunity with predominant
autoimmunity/autoinflammation into a comprehensive map of human immune
dysregulation which we termed “AutoCore”. The AutoCore is located
centrally within the interactome of all protein-protein interactions,
connecting and pinpointing multi-disease markers for a range of common,
polygenic autoimmune/autoinflammatory diseases. The AutoCore can be
subdivided into 19 endotypes that correspond to molecularly and
phenotypically cohesive disease subgroups, providing a molecular
mechanism-based disease classification and rationale towards systematic
targeting for therapeutic purposes. Our study provides a proof-of-concept
for using network-based methods to systematically investigate the
molecular relationships between individual rare diseases and address a
range of conceptual, diagnostic, and therapeutic challenges.