Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1

Scientific Reports
Nils LandegrenOlle Kämpe

Abstract

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

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Citations

Sep 7, 2016·Frontiers in Pediatrics·Lucia De MartinoMariacarolina Salerno
Sep 6, 2017·Immunology·Geraldo A PassosDaniella A Mendes-da-Cruz
Feb 15, 2020·Scandinavian Journal of Immunology·Alexander LindNils Landegren
Jun 22, 2018·Nature Immunology·Mickie Cheng, Mark S Anderson
Mar 21, 2018·Scientific Reports·Hanna D BremerHelene Hansson-Hamlin
May 28, 2019·The Journal of Clinical Endocrinology and Metabolism·Lara Frommer, George J Kahaly
Sep 2, 2017·Frontiers in Immunology·Dmytro FishmanPärt Peterson
Sep 15, 2020·The Journal of Biological Chemistry·Rebecca R Florke GeePatrick Ryan Potts
Feb 16, 2021·Frontiers in Immunology·Elise M N Ferré, Michail S Lionakis
Oct 25, 2017·Current Opinion in Immunology·Irina ProektMark S Anderson
Apr 28, 2019·The Journal of Allergy and Clinical Immunology·Daniel ErikssonNils Landegren
Jun 3, 2021·International Journal of Molecular Sciences·Elena N SavvateevaEkaterina A Troshina
Aug 22, 2021·Current Opinion in Immunology·Vasileios OikonomouMichail S Lionakis

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Methods Mentioned

BETA
protein array technology
proteome array
immunoprecipitation
PCR
protein array

Software Mentioned

GenePix® Pro microarray (
GOstat
Quantasoft
AIRE

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