Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins
High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for m...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2017-08-01
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Series: | Frontiers in Immunology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00976/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dmytro Fishman Dmytro Fishman Kai Kisand Christina Hertel Mike Rothe Anu Remm Maire Pihlap Priit Adler Priit Adler Jaak Vilo Jaak Vilo Aleksandr Peet Antonella Meloni Antonella Meloni Katarina Trebusak Podkrajsek Tadej Battelino Øyvind Bruserud Anette S. B. Wolff Eystein S. Husebye Nicolas Kluger Kai Krohn Annamari Ranki Hedi Peterson Hedi Peterson Adrian Hayday Pärt Peterson |
spellingShingle |
Dmytro Fishman Dmytro Fishman Kai Kisand Christina Hertel Mike Rothe Anu Remm Maire Pihlap Priit Adler Priit Adler Jaak Vilo Jaak Vilo Aleksandr Peet Antonella Meloni Antonella Meloni Katarina Trebusak Podkrajsek Tadej Battelino Øyvind Bruserud Anette S. B. Wolff Eystein S. Husebye Nicolas Kluger Kai Krohn Annamari Ranki Hedi Peterson Hedi Peterson Adrian Hayday Pärt Peterson Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins Frontiers in Immunology autoimmune regulator autoantibodies immune tolerance thymus autoantigen |
author_facet |
Dmytro Fishman Dmytro Fishman Kai Kisand Christina Hertel Mike Rothe Anu Remm Maire Pihlap Priit Adler Priit Adler Jaak Vilo Jaak Vilo Aleksandr Peet Antonella Meloni Antonella Meloni Katarina Trebusak Podkrajsek Tadej Battelino Øyvind Bruserud Anette S. B. Wolff Eystein S. Husebye Nicolas Kluger Kai Krohn Annamari Ranki Hedi Peterson Hedi Peterson Adrian Hayday Pärt Peterson |
author_sort |
Dmytro Fishman |
title |
Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins |
title_short |
Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins |
title_full |
Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins |
title_fullStr |
Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins |
title_full_unstemmed |
Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins |
title_sort |
autoantibody repertoire in apeced patients targets two distinct subgroups of proteins |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-08-01 |
description |
High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity. |
topic |
autoimmune regulator autoantibodies immune tolerance thymus autoantigen |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.00976/full |
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doaj-a2c87384b96b4e2e8bda6453106b0ee02020-11-24T22:32:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-08-01810.3389/fimmu.2017.00976288970Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of ProteinsDmytro Fishman0Dmytro Fishman1Kai Kisand2Christina Hertel3Mike Rothe4Anu Remm5Maire Pihlap6Priit Adler7Priit Adler8Jaak Vilo9Jaak Vilo10Aleksandr Peet11Antonella Meloni12Antonella Meloni13Katarina Trebusak Podkrajsek14Tadej Battelino15Øyvind Bruserud16Anette S. B. Wolff17Eystein S. Husebye18Nicolas Kluger19Kai Krohn20Annamari Ranki21Hedi Peterson22Hedi Peterson23Adrian Hayday24Pärt Peterson25Institute of Computer Science, University of Tartu, Tartu, EstoniaQuretec Ltd., Tartu, EstoniaInstitute of Biomedical and Translational Medicine, University of Tartu, Tartu, EstoniaImmunoQure AG, Düsseldorf, GermanyImmunoQure AG, Düsseldorf, GermanyInstitute of Biomedical and Translational Medicine, University of Tartu, Tartu, EstoniaInstitute of Biomedical and Translational Medicine, University of Tartu, Tartu, EstoniaInstitute of Computer Science, University of Tartu, Tartu, EstoniaQuretec Ltd., Tartu, EstoniaInstitute of Computer Science, University of Tartu, Tartu, EstoniaQuretec Ltd., Tartu, EstoniaChildren’s Clinic of Tartu University Hospital, Tartu, EstoniaPediatric Clinic II, Ospedale Microcitemico, Cagliari, ItalyDepartment of Biomedical and Biotechnological Science, University of Cagliari, Cagliari, ItalyDepartment of Pediatric Endocrinology, Diabetes and Metabolism, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, SloveniaDepartment of Pediatric Endocrinology, Diabetes and Metabolism, University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, SloveniaDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, NorwayDepartment of Clinical Science, University of Bergen, Bergen, Norway0Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland0Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland0Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, FinlandInstitute of Computer Science, University of Tartu, Tartu, EstoniaQuretec Ltd., Tartu, Estonia1Peter Gorer Department of Immunobiology, King’s College, Guy’s Hospital, London, United KingdomInstitute of Biomedical and Translational Medicine, University of Tartu, Tartu, EstoniaHigh titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00976/fullautoimmune regulatorautoantibodiesimmune tolerancethymusautoantigen |