SPAID: a comprehensive database for disease-specific autoantigens in autoimmune disorders

Autoimmune diseases (ADs) are chronic inflammatory disorders characterized by complex etiologies and significant diagnostic challenges. Although autoantigens are critical for precision diagnosis and therapy, much of the immunogenic landscape remains unexplored due to the historical focus on canonical proteins. Here, we developed SPAID ( https://spaid.renlab.cn ), a comprehensive resource for candidate autoantigen discovery across 14 ADs that integrates canonical and non-canonical proteins within a two-level evidence framework. The validated level contains proteins associated with experimentally confirmed epitopes from T-cell assays and major histocompatibility complex (MHC) ligand assays. The proteomics-based level contains proteins identified by mass spectrometry (MS) from human samples, further annotated with differential expression patterns, immunogenicity scores, and functional features to support candidate autoantigen discovery and further validation. By combining validated evidence with proteomics-based evidence, SPAID enables the comprehensive characterization of candidate autoantigen repertoires and facilitates mechanistic investigation into antigen origins and pathogenic recognition. Overall, SPAID provides a foundational resource for advancing antigen-centered research and developing novel diagnostic and therapeutic strategies in autoimmunity.