AUTOANTIBODIES AS BIOMARKERS FOR AUTOIMMUNE POLYGLANDULAR SYNDROME TYPE 1
Researchers at UCSF and the Chan Zuckerberg Biohub have identified multiple common autoantibody targets in APS1 patients through proteome-wide programmable phage-display.
The identification of autoantigens remains a critical challenge for understanding and treating autoimmune diseases. Autoimmune polyglandular syndrome type 1 (APS1) is a rare monogenic form of autoimmunity that presents with widespread T and B cell autoimmune responses to multiple organs. Although APS1 is rare, many autoantibodies in APS1 patients are observed in individuals with more common autoimmune diseases. Therefore, autoantibody discovery in individuals with APS1 can illuminate fundamental autoimmune disease pathogenesis and provide biomarkers for identifying those at risk for disease.
Stage of Research
The inventors have identified autoantibody targets for APS1 by employing high-throughput, proteome-wide phage immunoprecipitation sequencing (PhIP-Seq) of serum from a cohort of patients with APS1. This PhIP-Seq autoantibody survey identified a collection of novel APS1 autoantigens as well as numerous known APS1 autoantigens. The inventors interrogated the PhIP-Seq data for phenotypic associations, as the cohort of APS1 individuals was extensively phenotyped for 24 clinical manifestations, and validated seven novel autoantigens. The identification of clinically-correlated autoantigens has important implications for poorly understood manifestations of APS1.
Applications
- Autoantibody discovery to diagnose autoimmune diseases and identify tissues at risk of damage
Advantages
- Proteome-wide PhIP-Seq approach overcomes challenges in identifying autoantibodies with weak affinity for target antigen, or rare or low expression of the target antigen
- Programmable phage display can comprehensively cover all annotated proteins and their isoforms
- Reduced volume requirement for human serum
- Platform can be adapted for antigen discovery and to reveal identities of autoantibodies in other common autoimmune diseases
Stage of Development
Research – in vitro
Publications
PCT Publication WO2021138273
Vazquez SE, Ferre EMN, Scheel DW, Sunshine S, Miao B, Mandel-Brehm C, Quandt Z, Chan AY, Cheng M, German M, Lionakis M, DeRisi JL, Anderson MS. Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by proteome-wide PhIP-Seq. 2020. eLife. Doi: 10.7554/eLife.55053
Related Web Links
https://derisilab.ucsf.edu/
Keywords
Autoantibody, Antibody, Diagnosis, Particle Display, Serum
Technology Reference
CZB-136F, SF2020-051