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

2017; Rockefeller University Press; Volume: 214; Issue: 9 Linguagem: Inglês

10.1084/jem.20161810

1540-9538

Tobias Schwerd, Stephen R.F. Twigg, Dominik Aschenbrenner, Santiago Manrique, Kerry A. Miller, Indira B. Taylor, Melania Capitani, Simon J. McGowan, Elizabeth Sweeney, Astrid Weber, Liye Chen, Paul Bowness, Andrew Riordan, Andrew J. Cant, Alexandra F. Freeman, Joshua D. Milner, Steven M. Holland, Natalie Frede, Miryam Müller, Dirk Schmidt‐Arras, Bodo Grimbacher, Steven A. Wall, E. Yvonne Jones, Andrew O.M. Wilkie, Holm H. Uhlig,

Blood disorders and treatments

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.