A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis

Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recu...

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Detalles Bibliográficos
Autores principales: Schwerd, Tobias, Twigg, Stephen R.F., Aschenbrenner, Dominik, Manrique, Santiago, Miller, Kerry A., Taylor, Indira B., Capitani, Melania, McGowan, Simon J., Sweeney, Elizabeth, Weber, Astrid, Chen, Liye, Bowness, Paul, Riordan, Andrew, Cant, Andrew, Freeman, Alexandra F., Milner, Joshua D., Holland, Steven M., Frede, Natalie, Müller, Miryam, Schmidt-Arras, Dirk, Grimbacher, Bodo, Wall, Steven A., Jones, E. Yvonne, Wilkie, Andrew O.M., Uhlig, Holm H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Research Articles
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584118/
https://www.ncbi.nlm.nih.gov/pubmed/28747427
http://dx.doi.org/10.1084/jem.20161810
Descripción
Sumario:Multiple cytokines, including interleukin 6 (IL-6), IL-11, IL-27, oncostatin M (OSM), and leukemia inhibitory factor (LIF), signal via the common GP130 cytokine receptor subunit. In this study, we describe a patient with a homozygous mutation of IL6ST (encoding GP130 p.N404Y) who presented with recurrent infections, eczema, bronchiectasis, high IgE, eosinophilia, defective B cell memory, and an impaired acute-phase response, as well as skeletal abnormalities including craniosynostosis. The p.N404Y missense substitution is associated with loss of IL-6, IL-11, IL-27, and OSM signaling but a largely intact LIF response. This study identifies a novel immunodeficiency with phenotypic similarities to STAT3 hyper-IgE syndrome caused by loss of function of GP130.

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