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Sci Rep. 2016 Feb 1;6:20104. doi: 10.1038/srep20104.

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

Author information

1
Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Sweden.
2
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.
3
Department of Genetics, Stanford University, California, USA.
4
Department of Molecular, Cellular, and Developmental Biology, Yale University, Connecticut, USA.
5
Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Sweden.
6
Bioinformatics Infrastructure for Life Sciences, Sweden.
7
Department of Immunology, Genetics and Pathology, Uppsala University, Sweden and Science for Life Laboratory, Uppsala, Sweden.
8
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
9
Department of Endocrinology and Department of Medical and Health Sciences and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
10
Integrative Reproductive Medicine Group, Intramural Research Program on Reproductive and Adult Endocrinology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
11
Department of Women's and Children's Health, Uppsala University, Sweden.
12
Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital, Bergen, Norway.
13
Diabetes Center, University of California San Francisco, USA.

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.

PMID:
26830021
PMCID:
PMC4735587
DOI:
10.1038/srep20104
[Indexed for MEDLINE]
Free PMC Article

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