title: Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.
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.
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Sweden.|Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Landegren
authors.affiliation: Department of Genetics, Stanford University, California, USA.|Department of Molecular, Cellular, and Developmental Biology, Yale University, Connecticut, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Sharon
authors.affiliation: Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.|Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Sweden.|Bioinformatics Infrastructure for Life Sciences, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Freyhult
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Sweden.|Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Hallgren
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Sweden.|Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Eriksson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Sweden and Science for Life Laboratory, Uppsala, Sweden.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Bensing
authors.affiliation: Department of Endocrinology and Department of Medical and Health Sciences and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wahlberg
authors.affiliation: 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.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Nelson
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.affiliation: Department of Clinical Science, University of Bergen, and Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Husebye
authors.affiliation: Diabetes Center, University of California San Francisco, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Anderson
authors.affiliation: Department of Genetics, Stanford University, California, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.affiliation: Department of Medicine (Solna), Karolinska University Hospital, Karolinska Institutet, Sweden.|Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000097:blood / Q000276:immunology*; D040081:Protein Array Analysis; D019704:Protein Disulfide-Isomerases / Q000097:blood / Q000276:immunology*; D020543:Proteome / Q000276:immunology* / Q000378:metabolism; D012537:Scandinavian and Nordic Countries
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D001324:Autoantigens; C072012:MAGEB2 protein, human; D009363:Neoplasm Proteins; D020543:Proteome; C496702:PDILT protein, human; D019704:Protein Disulfide-Isomerases
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