Autoantibody repertoire in APECED patients targets two distinct subgroups of proteins
journal contributionposted on 2020-08-12, 13:40 authored by 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 SB Wolff, Eystein S Husebye, Nicolas Kluger, Kai Krohn, Annamari Ranki, Hedi Peterson, Adrian Hayday, Pärt Peterson
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.