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Fishman D, Kisand K, Hertel C, et al. Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins. Front Immunol. 2017;8:976doi: 10.3389/fimmu.2017.00976.
Fishman, D., Kisand, K., Hertel, C., Rothe, M., Remm, A., Pihlap, M., Adler, P., Vilo, J., Peet, A., Meloni, A., Podkrajsek, K. T., Battelino, T., Bruserud, �. �., Wolff, A. S. B., Husebye, E. S., Kluger, N., Krohn, K., Ranki, A., Peterson, H., Hayday, A., & Peterson, P. (2017). Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins. Frontiers in immunology, 8976. https://doi.org/10.3389/fimmu.2017.00976
Fishman, Dmytro, et al. "Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins." Frontiers in immunology vol. 8 (2017): 976. doi: https://doi.org/10.3389/fimmu.2017.00976
Fishman D, Kisand K, Hertel C, Rothe M, Remm A, Pihlap M, Adler P, Vilo J, Peet A, Meloni A, Podkrajsek KT, Battelino T, Bruserud Ø, Wolff ASB, Husebye ES, Kluger N, Krohn K, Ranki A, Peterson H, Hayday A, Peterson P. Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins. Front Immunol. 2017 Aug 16;8:976. doi: 10.3389/fimmu.2017.00976. eCollection 2017. PMID: 28861084; PMCID: PMC5561390.
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Front Immunol. 2017 Aug 16;8:976. doi: 10.3389/fimmu.2017.00976. eCollection 2017.

Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins.

Frontiers in immunology

Dmytro Fishman, Kai Kisand, Christina Hertel, Mike Rothe, Anu Remm, Maire Pihlap, Priit Adler, Jaak Vilo, Aleksandr Peet, Antonella Meloni, Katarina Trebusak Podkrajsek, Tadej Battelino, Øyvind Bruserud, Anette S B Wolff, Eystein S Husebye, Nicolas Kluger, Kai Krohn, Annamari Ranki, Hedi Peterson, Adrian Hayday, Pärt Peterson

Affiliations

  1. Institute of Computer Science, University of Tartu, Tartu, Estonia.
  2. Quretec Ltd., Tartu, Estonia.
  3. Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia.
  4. ImmunoQure AG, Düsseldorf, Germany.
  5. Children's Clinic of Tartu University Hospital, Tartu, Estonia.
  6. Pediatric Clinic II, Ospedale Microcitemico, Cagliari, Italy.
  7. Department of Biomedical and Biotechnological Science, University of Cagliari, Cagliari, Italy.
  8. Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
  9. Department of Clinical Science, University of Bergen, Bergen, Norway.
  10. Department of Dermatology, Allergology and Venereology, Institute of Clinical Medicine, University of Helsinki, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland.
  11. Peter Gorer Department of Immunobiology, King's College, Guy's Hospital, London, United Kingdom.

PMID: 28861084 PMCID: PMC5561390 DOI: 10.3389/fimmu.2017.00976

Abstract

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.

Keywords: autoantibodies; autoantigen; autoimmune regulator; immune tolerance; thymus

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