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Interferon autoantibodies associated with AIRE-deficiency decrease the expression of IFN-stimulated genes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Autoimmuna sjukdomar (Kämpe))
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. (Autoimmuna sjukdomar (Kämpe))
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2008 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 112, no 7, 2657-2666 p.Article in journal (Refereed) Published
Abstract [en]

Neutralizing autoantibodies to type I, but not type II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead to defects in thymic T-cell selection. Combining genome-wide expression array with real time RT-PCR assays, we here demonstrate that antibodies against IFN-alpha cause highly significant down-regulation of interferon-stimulated gene expression in cells from APECED patients' blood by blocking their highly dilute endogenous IFNs. This down-regulation was lost progressively as these APECED cells matured in cultures without neutralizing autoantibodies. Most interestingly, a rare APECED patient with autoantibodies to IFN-omega but not IFN-alpha showed a marked increase in expression of the same interferon-stimulated genes. We also report unexpected increases in serum CXCL10 levels in APECED. Our results argue that the breakdown of tolerance to IFNs in AIRE deficiency is associated with impaired responses to them in thymus, and highlight APECED as another autoimmune disease with associated dysregulation of IFN activity.

Place, publisher, year, edition, pages
2008. Vol. 112, no 7, 2657-2666 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-17670DOI: 10.1182/blood-2008-03-144634ISI: 000259402600018PubMedID: 18606876OAI: oai:DiVA.org:uu-17670DiVA: diva2:45441
Available from: 2008-08-12 Created: 2008-08-12 Last updated: 2010-05-06Bibliographically approved

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Lobell, AnnaKämpe, Olle
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