AUTHOR=Fishman Dmytro , Kisand Kai , Hertel Christina , Rothe Mike , Remm Anu , Pihlap Maire , Adler Priit , Vilo Jaak , Peet Aleksandr , Meloni Antonella , Podkrajsek Katarina Trebusak , Battelino Tadej , Bruserud Øyvind , Wolff Anette S. B. , Husebye Eystein S. , Kluger Nicolas , Krohn Kai , Ranki Annamari , Peterson Hedi , Hayday Adrian , Peterson Pärt TITLE=Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00976 DOI=10.3389/fimmu.2017.00976 ISSN=1664-3224 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.