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

被引：154

作者：

Schwerd, Tobias ^{[1
,8
]}

Twigg, Stephen R. F. ^{[2
]}

Aschenbrenner, Dominik ^{[1
]}

Manrique, Santiago ^{[3
]}

Miller, Kerry A. ^{[2
]}

Taylor, Indira B. ^{[2
]}

Capitani, Melania ^{[1
]}

McGowan, Simon J. ^{[4
]}

Sweeney, Elizabeth ^{[9
]}

Weber, Astrid ^{[9
]}

Chen, Liye ^{[5
]}

Bowness, Paul ^{[5
]}

Riordan, Andrew ^{[10
]}

Cant, Andrew ^{[11
]}

Freeman, Alexandra F. ^{[12
]}

Milner, Joshua D. ^{[13
]}

Holland, Steven M. ^{[12
]}

Frede, Natalie ^{[14
]}

Mueller, Miryam ^{[15
]}

Schmidt-Arras, Dirk ^{[15
]}

Grimbacher, Bodo ^{[14
,16
]}

Wall, Steven A. ^{[6
]}

Jones, E. Yvonne ^{[3
]}

Wilkie, Andrew O. M. ^{[2
,6
]}

Uhlig, Holm H. ^{[1
,7
]}

机构：

[1] Univ Oxford, Translat Gastroenterol Unit, John Radcliffe Hosp, Oxford, England

[2] Univ Oxford, Clin Genet Grp, John Radcliffe Hosp, MRC Weatherall Inst Mol Med, Oxford, England

[3] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford, England

[4] Univ Oxford, Computat Biol Res Grp, MRC Weatherall Inst Mol Med, John Radcliffe Hosp, Oxford, England

[5] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford, England

[6] Univ Oxford, Craniofacial Unit, Dept Plast & Reconstruct Surg, Oxford Univ Hosp Natl Hlth Serv Fdn Trust,John Ra, Oxford, England

[7] Univ Oxford, Dept Paediat, Oxford, England

[8] Ludwig Maximilians Univ Munchen, Dr von Hauner Childrens Hosp, Munich, Germany

[9] Liverpool Womens Natl Hlth Serv Fdn Trust, Dept Clin Genet, Liverpool, Merseyside, England

[10] Alder Hey Childrens Natl Hlth Serv Fdn Trust, Dept Paediat Infect Dis & Immunol, Liverpool, Merseyside, England

[11] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[12] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[13] NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[14] Univ Klinikum Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany

[15] Christian Albrechts Univ Kiel, Inst Biochem, Inflammat & Canc Lab, Kiel, Germany

[16] UCL, Royal Free Hosp, Inst Immunol & Transplantat, London, England

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

HYPER-IGE-SYNDROME; TARGETED DISRUPTION; INTERLEUKIN-6; FAMILY; RECURRENT INFECTIONS; SIGNAL TRANSDUCER; T-CELLS; STAT3; DEFICIENCY; DIFFERENTIATION; IMMUNITY;

D O I：

10.1084/jem.20161810

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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 syndrome caused by loss of function of GP130.

引用

页码：2547 / 2562

页数：16

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