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

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.

SUBMITTER: Fishman D

PROVIDER: S-EPMC5561390 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Fishman Dmytro D Kisand Kai K Hertel Christina C Rothe Mike M Remm Anu A Pihlap Maire M Adler Priit P Vilo Jaak J Peet Aleksandr A Meloni Antonella A Podkrajsek Katarina Trebusak KT Battelino Tadej T Bruserud Øyvind Ø Wolff Anette S B ASB Husebye Eystein S ES Kluger Nicolas N Krohn Kai K Ranki Annamari A Peterson Hedi H Hayday Adrian A Peterson Pärt P

Frontiers in immunology 20170816

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-produc ...[more]

PMID: 28861084

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

Publications

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

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