NDLI: Anti-Cytokine Autoantibodies Preceding Onset of Autoimmune Polyendocrine Syndrome Type I Features in Early Childhood

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Anti-Cytokine Autoantibodies Preceding Onset of Autoimmune Polyendocrine Syndrome Type I Features in Early Childhood

Content Provider	Springer Nature Link
Author	Wolff, A. S. B. Sarkadi, A. K. Maródi, L. Kärner, J. Orlova, E. Oftedal, B. E. V. Kisand, K. Oláh, É. Meloni, A. Myhre, A. G. Husebye, E. S. Motaghedi, R. Perheentupa, J. Peterson, P. Willcox, N. Meager, A.
Copyright Year	2013
Abstract	Almost all patients with autoimmune polyendocrine syndrome (APS)-I have high titer neutralizing autoantibodies to type I interferons (IFN), especially IFN-ω and IFN-α2, whatever their clinical features and onset-ages. About 90 % also have antibodies to interleukin (IL)-17A, IL-17F and/or IL-22; they correlate with the chronic mucocutaneous candidiasis (CMC) that affects ~90 % of patients. Our aim was to explore how early the manifestations and endocrine and cytokine autoantibodies appear in young APS-I patients. That may hold clues to very early events in the autoimmunization process in these patients.Clinical investigations and autoantibody measurements in 13 APS-I patients sampled before age 7 years, and 3 pre-symptomatic siblings with AIRE-mutations in both alleles.Antibody titers were already high against IFN-α2 and IFN-ω at age 6 months in one sibling—8 months before onset of APS-I—and also against IL-22 at 7 months in another (still unaffected at age 5 years). In 12 of the 13 APS-I patients, antibody levels were high against IFN-ω and/or IL-22 when first tested, but only modestly positive against IFN-ω in one patient who had only hypo-parathyroidism. Endocrine organ-specific antibodies were present at age 6 months in one sibling, and as early as 36 and 48 months in two of the six informative subjects.This is the first study to collate the onset of clinical features, cytokine and endocrine autoantibodies in APS-I infants and siblings. The highly restricted early autoantibody responses and clinical features they show are not easily explained by mere loss of broad-specific self-tolerance inducing mechanisms, but hint at some more sharply focused early event(s) in autoimmunization.
Starting Page	1341
Ending Page	1348
Page Count	8
File Format	PDF
ISSN	02719142
Journal	Journal of Clinical Immunology
Volume Number	33
Issue Number	8
e-ISSN	15732592
Language	English
Publisher	Springer US
Publisher Date	2013-10-26
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	APECED AIRE autoimmune polyendocrine syndrome autoimmune immuno-deficiency cytokine autoantibodies Interferon omega Interleukin 22 Interleukin 17 candidiasis autoimmunization Immunology Infectious Diseases Internal Medicine Medical Microbiology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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