Identification of novel, clinically correlated autoantigens in the monogenic autoimmune syndrome APS1 by PhIP-Seq

Abstract

40The identification of autoantigens remains a critical challenge for understanding and treating 41 autoimmune diseases. Autoimmune polyendocrine syndrome type 1 (APS1), a rare monogenic 42 form of autoimmunity, presents as widespread autoimmunity with T and B cell responses to 43 multiple organs. Importantly, autoantibody discovery in APS1 can illuminate fundamental disease 44 pathogenesis, and many of the antigens found in APS1 extend to common autoimmune diseases. 45Here, we performed proteome-wide programmable phage-display (PhIP-Seq) on sera from an 46 APS1 cohort and discovered multiple common antibody targets. These novel autoantigens exhibit 47 102 over previous candidate-based and whole-protein fixed array approaches, including (1) expanded, 103 proteome-wide coverage (including alternative splice forms) with 49 amino acid (AA) peptide 104 length and 24AA resolution tiling, (2) reduced volume requirement for human serum, and (3) high-105

Proteome-wide antigenic profiling in Ugandan cohorts identifies associations between age, exposure intensity, and responses to repeat-containing antigens in Plasmodium falciparum

“…Here, we customized a programmable phage display system (PhIP-seq) (Larman et al, 2011), previously used for antigenic profiling in many diseases, including autoimmune disorders and viral infections (Mandel-Brehm et al, 2019;Rajan et al, 2021;Vazquez et al, 2020;Zamecnik et al, 2020), for interrogation of the humoral response to P. falciparum infection. We designed a custom library ("Falciparome") that features over 238,000 individual 62 amino acid peptides encoded in T7 Phage, tiled every 25 amino acids across all annotated P. falciparum open reading frames from 3D7/IT genomes with additional variant antigenic sequences.…”