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

J Exp Med.. 2017-09;

Schwerd T, Twigg SRF, Aschenbrenner D, Manrique S, Miller KA, Taylor IB, Capitani M, McGowan SJ, Sweeney E, Weber A, Chen L, Bowness P, Riordan A, Cant A, Freeman AF0, Milner JD, Holland SM0, Frede N, Müller M, Schmidt-Arras D, Grimbacher B, Wall SA, Jones EY, Wilkie AOM, Uhlig HH.

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PCR Cloning and Subcloning	... IL-11RA were cloned into the pcDNA3.1(+) vector without C- or N-terminal tags (GenScript). Sequences were verified by Sanger sequencing after each transformation step. The. ...	Get A Quote

摘要

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 ... More