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

Abstract

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.

• Authors: 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 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
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 214 Issue 9 Pg. 2547-2562 (Sep 04 2017) ISSN: 1540-9538 [Electronic] United States
• PMID: 28747427 (Publication Type: Journal Article)
• Copyright: © 2017 Schwerd et al.

Chemical References

• IL11 protein, human
• IL6ST protein, human
• Interleukin-11
• Interleukin-6
• Interleukins
• MYDGF protein, human
• Cytokine Receptor gp130

Topics

• Child, Preschool
• Craniosynostoses (genetics)
• Cytokine Receptor gp130 (genetics, physiology)
• Exome (genetics)
• Female
• Humans
• Immunologic Deficiency Syndromes (genetics)
• Interleukin-11 (deficiency)
• Interleukin-6 (deficiency)
• Interleukins (deficiency)
• Mutation, Missense (genetics)