The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines
Open accessAbstract
Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in >150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.
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Cites
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Positional cloning of the APECED gene
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Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells
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“Because IL-22 especially protects epithelial surfaces (Liang et al., 2006; Aujla and Kolls, 2009) and IL-22+/IL17 cells show skin-homing properties (Duhen et al., 2009; Trifari et al., 2009), our findings may help to explain the mucocutaneous rather than systemic focus of the candidiasis in both…”
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BackgroundInfluential
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Metadata
- Authors
- Kisand, K., Bøe Wolff, A. S., Podkrajšek, K. T., Tserel, L., Link, M., Kisand, K. V., Ersvaer, E., Perheentupa, J., Erichsen, M. M., Bratanic, N., Meloni, A., Cetani, F., Perniola, R., Ergun-Longmire, B., Maclaren, N., Krohn, K. J. E., Pura, M., Schalke, B., Ströbel, P., Leite, M. I., Battelino, T., Husebye, E. S., Peterson, P., Willcox, N., & Meager, A.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2010-02-01
- Volume
- 207
- Issue
- 2
- Pages
- 299-308
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2164082708
- Cited by
- 677
- References
- 42
- FWCI
- 22.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kisand, K., Bøe Wolff, A. S., Podkrajšek, K. T., Tserel, L., Link, M., Kisand, K. V., Ersvaer, E., Perheentupa, J., Erichsen, M. M., Bratanic, N., Meloni, A., Cetani, F., Perniola, R., Ergun-Longmire, B., Maclaren, N., Krohn, K. J. E., Pura, M., Schalke, B., Ströbel, P., . . . Meager, A. (2010). Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20091669
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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