AIRE-Deficient Patients Harbor Unique High-Affinity Disease-Ameliorating Autoantibodies.
Cell
; 166(3): 582-595, 2016 Jul 28.
Article
em En
| MEDLINE
| ID: mdl-27426947
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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Fatores de Transcrição
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Poliendocrinopatias Autoimunes
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Resistência à Doença
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Afinidade de Anticorpos
Limite:
Adolescent
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Adult
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Aged
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Animals
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Child
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Child, preschool
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article