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Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1
Karolinska Institute, Sweden; Uppsala University, Sweden.
Stanford University, CA 94305 USA; Yale University, CT 06520 USA.
Uppsala University, Sweden; Uppsala University, Sweden.
Karolinska Institute, Sweden; Uppsala University, Sweden.
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 20104Article in journal (Refereed) PublishedText
Abstract [en]

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 AIREs 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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2016. Vol. 6, no 20104
National Category
Health Sciences
URN: urn:nbn:se:liu:diva-125308DOI: 10.1038/srep20104ISI: 000368996700001PubMedID: 26830021OAI: diva2:906362

Funding Agencies|Swedish Research Council; Formas Research Council; Torsten Soderberg Foundation; Ragnar Soderberg Foundation; Novonordisk Foundation; Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

Available from: 2016-02-24 Created: 2016-02-19 Last updated: 2016-03-15

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Wahlberg Topp, Jeanette
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Department of Medical and Health SciencesDepartment of EndocrinologyFaculty of Medicine and Health Sciences
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