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

Sci Adv 2023 Sep;9(35):eadg6375
PMID: DOI: 10.1126/sciadv.adg6375
Sci Adv 2023 Sep;9(35):eadg6375
PMID: DOI: 10.1126/sciadv.adg6375

Although research on rare autoimmune and autoinflammatory diseases has enabled definition of nonredundant regulators of homeostasis in human immunity, because of the single gene-single disease nature of many of these diseases, contributing factors were mostly unveiled in sequential and noncoordinated individual studies. 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 multidisease 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 toward 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.

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