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https://hdl.handle.net/2440/52205
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Type: | Journal article |
Title: | Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes |
Author: | Kisand, K. Link, M. Wolff, A. Meager, A. Tserel, L. Org, T. Murumagi, A. Uibo, R. Willcox, N. Podkrajek, K. Battelino, T. Lobell, A. Kampe, O. Lima, K. Meloni, A. Ergun-Longmire, B. Maclaren, N. Perheentupa, J. Krohn, K. Scott, H. et al. |
Citation: | Blood, 2008; 112(7):2657-2666 |
Publisher: | Amer Soc Hematology |
Issue Date: | 2008 |
ISSN: | 0006-4971 1528-0020 |
Statement of Responsibility: | Kai Kisand, ... Hamish S. Scott, et al. |
Abstract: | 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. |
Keywords: | Dendritic Cells Blood Cells Monocytes Cell Line Humans Polyendocrinopathies, Autoimmune Interferons Interferon Type I Transcription Factors Autoantibodies Neutralization Tests Oligonucleotide Array Sequence Analysis Case-Control Studies Down-Regulation Phosphorylation Models, Immunological Adolescent Adult Middle Aged Female Male STAT1 Transcription Factor Chemokine CXCL10 |
DOI: | 10.1182/blood-2008-03-144634 |
Published version: | http://dx.doi.org/10.1182/blood-2008-03-144634 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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