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.

多种细胞因子，包括白介素6（IL-6），IL-11，IL-27，制瘤素M（OSM）和白血病抑制因子（LIF），通过共同的GP130细胞因子受体亚基发出信号。在这项研究中，我们描述了一个具有IL6ST纯合突变（编码GP130 p.N404Y）的患者，该患者表现为反复感染，湿疹，支气管扩张，高IgE，嗜酸性粒细胞增多，B细胞记忆缺陷以及急性期反应受损，以及骨骼异常，包括颅突。p.N404Y错义替换与IL-6，IL-11，IL-27和OSM信号转导缺失有关，但与LIF反应基本保持一致。这项研究确定了一种新的免疫缺陷病，其表型相似性是由GP130功能丧失引起的STAT3高IgE综合征。