AIRE-deficient patients harbor unique high-affinity disease-ameliorating autoantibodies
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[1] King's College
King's College
City of Wilkes-Barre, Estados Unidos
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[2] ImmunoQure AG
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- Localización: Cell, ISSN 0092-8674, Vol. 166, Nº. 3, 2016, págs. 582-595
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
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.
