Human Autoantigen Atlas: Searching for the Hallmarks of Autoantigens

Area of Science:

• Immunology
• Bioinformatics
• Genomics

Background:

• Autoimmunity to endogenous proteins is critical for diagnosing and treating autoimmune diseases.
• Identifying autoantigens (AAgs) and their roles in disease is essential for therapeutic development.

Purpose of the Study:

• To develop a comprehensive resource, AAgAtlas, for exploring human autoantigens and their associated diseases.
• To systematically analyze the immunogenic properties and characteristics of human autoantigens.

Main Methods:

• Development of the AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#) to curate and search 8,045 non-redundant AAgs and 47 post-translationally modified AAgs against 1,073 human diseases.
• Utilizing genetic, biophysical, cytological, expression profile, and evolutionary data to elucidate AAg immunogenic properties.
• Performing genome, transcriptome, and proteome analyses to investigate the association of autoantibody (AAb) production with genetic variations and protein expression.

Main Results:

• Human AAgs are evolutionarily conserved and enriched in hydrophilic amino acids (K, D, E) on protein surfaces.
• AAgs are frequently found in proteins involved in nucleic acid binding, transferase activity, and the cytoskeleton.
• AAb production correlates with gene variance and abnormal protein expression in various tumor pathologies.

Conclusions:

• The AAgAtlas portal provides a valuable resource for studying human autoantigens and their link to diseases.
• Characterizing autoantigen hallmarks advances the understanding of humoral autoimmunity.
• Identified autoantigen features can aid in the discovery of novel biomarkers for human diseases.