TY - JOUR AU - Fishman, Dmytro AU - Kisand, Kai AU - Hertel, Christina AU - Rothe, Mike AU - Remm, Anu AU - Pihlap, Maire AU - Adler, Priit AU - Vilo, Jaak AU - Peet, Aleksandr AU - Meloni, Antonella AU - Podkrajsek, Katarina Trebusak AU - Battelino, Tadej AU - Bruserud, Øyvind AU - Wolff, Anette S. B. AU - Husebye, Eystein S. AU - Kluger, Nicolas AU - Krohn, Kai AU - Ranki, Annamari AU - Peterson, Hedi AU - Hayday, Adrian AU - Peterson, Pärt PY - 2017 M3 - Original Research TI - Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Proteins JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2017.00976 VL - 8 SN - 1664-3224 N2 - 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. ER -