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Autoantibodies against IL-17A, IL-17F and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I

Lookup NU author(s): Professor Andrew Cant, Dr Mario Abinun, Dr Desa Lilic

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Abstract

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1β, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-β, tumor necrosis factor [], or transforming growth factor β). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.


Publication metadata

Author(s): Puel A, Natividad A, Chrabieh M, Döffinger R, Barcenas-Morales G, Picard C, Ouachée-Chardin M, Toulon A, Bustamante J, Al-Muhsen S, Arkwright PD, Costigan C, McConnell V, Cant AJ, Abinun M, Polak M, Bougnères PF, Kumararatne D, Blanche S, Fischer AM, Bodemer C, Abel L, Lilic D, Casanova JL

Publication type: Article

Publication status: Published

Journal: Journal of Experimental Medicine

Year: 2010

Volume: 207

Issue: 2

Pages: 291-297

Print publication date: 15/02/2010

Date deposited: 10/06/2011

ISSN (print): 0022-1007

ISSN (electronic): 1540-9538

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1084/jem.20091983

DOI: 10.1084/jem.20091983

Notes: D. Lilic and J.-L. Casanova have shared senior authorship of this article. See also Editorial from this journal issue: Maxmen, A. Antibodies attack IL-17. Journal of Experimental Medicine 2010, 207(2): 264-265.


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Funding

Funder referenceFunder name
Agence Nationale de la Recherche
University Paris Descartes
Addenbrooke's Charitable Trust
Dana Foundation
European Union
Howard Hughes Medical Institute
Hungarian Scientific Research Fund
Institut National de la Sante et de la Recherche Medicale
March of Dimes
National Institute for Health Research Cambridge Biomedical Research Center
5UL1RR024143-03Rockefeller University Center for Clinical and Translational Science

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