AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies

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http://hdl.handle.net/10138/166271

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Meyer , S , Woodward , M , Hertel , C , Vlaicu , P , Haque , Y , Karner , J , Macagno , A , Onuoha , S C , Fishman , D , Peterson , H , Metskula , K , Uibo , R , Jäntti , K , Hokynar , K , Wolff , A S B , Krohn , K , Ranki , A , Peterson , P , Kisand , K , Hayday , A & APECED Patient Collaborative 2016 , ' AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies ' , Cell , vol. 166 , no. 3 , pp. 582-595 . https://doi.org/10.1016/j.cell.2016.06.024

Title: AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies
Author: Meyer, Steffen; Woodward, Martin; Hertel, Christina; Vlaicu, Philip; Haque, Yasmin; Karner, Jaanika; Macagno, Annalisa; Onuoha, Shimobi C.; Fishman, Dmytro; Peterson, Hedi; Metskula, Kaja; Uibo, Raivo; Jäntti, Kirsi; Hokynar, Kati; Wolff, Anette S. B.; Krohn, Kai; Ranki, Annamari; Peterson, Part; Kisand, Kai; Hayday, Adrian; APECED Patient Collaborative
Contributor: University of Helsinki, HYKS-instituutti Oy
University of Helsinki, HYKS-instituutti Oy
University of Helsinki, Clinicum
Date: 2016-07-28
Language: eng
Number of pages: 14
Belongs to series: Cell
ISSN: 0092-8674
URI: http://hdl.handle.net/10138/166271
Abstract: APS1/APECED patients are defined by defects in the autoimmune regulator (AIRE) that mediates central T cell tolerance to many self-antigens. AIRE deficiency also affects B cell tolerance, but this is incompletely understood. Here we show that most APS1/APECED patients displayed B cell autoreactivity toward unique sets of approximately 100 self-proteins. Thereby, autoantibodies from 81 patients collectively detected many thousands of human proteins. The loss of B cell tolerance seemingly occurred during antibody affinity maturation, an obligatorily T cell-dependent step. Consistent with this, many APS1/APECED patients harbored extremely high-affinity, neutralizing autoantibodies, particularly against specific cytokines. Such antibodies were biologically active in vitro and in vivo, and those neutralizing type I interferons (IFNs) showed a striking inverse correlation with type I diabetes, not shown by other anti-cytokine antibodies. Thus, naturally occurring human autoantibodies may actively limit disease and be of therapeutic utility.
Subject: SYNDROME TYPE-I
POLYENDOCRINE SYNDROME TYPE-1
CHRONIC MUCOCUTANEOUS CANDIDIASIS
NONOBESE DIABETIC MICE
B-CELLS
ADDISONS-DISEASE
CYTOCHROME-P450 ENZYMES
TOLERANCE INDUCTION
INTERFERON-ALPHA
GENE
3121 General medicine, internal medicine and other clinical medicine
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