Please use this identifier to cite or link to this item: http://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
RMID: 0020082739
DOI: 10.1182/blood-2008-03-144634
Appears in Collections:Medicine publications

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