Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Sarah Spencer; Sevgi Köstel Bal; William Egner; Hana Lango Allen; Syed I. Raza; Chi A. Ma; Meltem Gürel; Yuan Zhang; Guangping Sun; Ruth A. Sabroe; Daniel Greene; William Rae; Tala Shahin; Katarzyna Kania; Rico Chandra Ardy; Marini Thian; Emily Staples; Annika Pecchia-Bekkum; William P.M. Worrall; Jonathan Stephens; Matthew Brown; Salih Tuna; Melanie York; Fiona Shackley; Diarmuid Kerrin; Ravishankar Sargur; Alison Condliffe; Hamid Nawaz Tipu; Hye Sun Kuehn; Sergio D. Rosenzweig; Ernest Turro; Simon Tavaré; Adrian J. Thrasher; Duncan Ian Jodrell; Kenneth G.C. Smith; Kaan Boztug; Joshua D. Milner; James E.D. Thaventhiran

doi:10.1084/jem.20190344

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Sarah Spencer, Sevgi Köstel Bal, William Egner, Hana Lango Allen, Syed I. Raza, Chi A. Ma, Meltem Gürel, Yuan Zhang, Guangping Sun, Ruth A. Sabroe, Daniel Greene, William Rae, Tala Shahin, Katarzyna Kania, Rico Chandra Ardy, Marini Thian, Emily Staples, Annika Pecchia-Bekkum, William P.M. Worrall, Jonathan StephensMatthew Brown, Salih Tuna, Melanie York, Fiona Shackley, Diarmuid Kerrin, Ravishankar Sargur, Alison Condliffe, Hamid Nawaz Tipu, Hye Sun Kuehn, Sergio D. Rosenzweig, Ernest Turro, Simon Tavaré, Adrian J. Thrasher, Duncan Ian Jodrell, Kenneth G.C. Smith, Kaan Boztug, Joshua D. Milner, James E.D. Thaventhiran

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Abstract

IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.

Original language	English
Pages (from-to)	1986-1998
Number of pages	13
Journal	Journal of Experimental Medicine
Volume	216
Issue number	9
DOIs	https://doi.org/10.1084/jem.20190344
State	Published - 1 Sep 2019
Externally published	Yes

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Spencer, S., Bal, S. K., Egner, W., Allen, H. L., Raza, S. I., Ma, C. A., Gürel, M., Zhang, Y., Sun, G., Sabroe, R. A., Greene, D., Rae, W., Shahin, T., Kania, K., Ardy, R. C., Thian, M., Staples, E., Pecchia-Bekkum, A., Worrall, W. P. M., ... Thaventhiran, J. E. D. (2019). Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. Journal of Experimental Medicine, 216(9), 1986-1998. https://doi.org/10.1084/jem.20190344

@article{76d176e942b8402dafa2194145ba2ee9,

title = "Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses",

abstract = "IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.",

author = "Sarah Spencer and Bal, \{Sevgi K{\"o}stel\} and William Egner and Allen, \{Hana Lango\} and Raza, \{Syed I.\} and Ma, \{Chi A.\} and Meltem G{\"u}rel and Yuan Zhang and Guangping Sun and Sabroe, \{Ruth A.\} and Daniel Greene and William Rae and Tala Shahin and Katarzyna Kania and Ardy, \{Rico Chandra\} and Marini Thian and Emily Staples and Annika Pecchia-Bekkum and Worrall, \{William P.M.\} and Jonathan Stephens and Matthew Brown and Salih Tuna and Melanie York and Fiona Shackley and Diarmuid Kerrin and Ravishankar Sargur and Alison Condliffe and Tipu, \{Hamid Nawaz\} and Kuehn, \{Hye Sun\} and Rosenzweig, \{Sergio D.\} and Ernest Turro and Simon Tavar{\'e} and Thrasher, \{Adrian J.\} and Jodrell, \{Duncan Ian\} and Smith, \{Kenneth G.C.\} and Kaan Boztug and Milner, \{Joshua D.\} and Thaventhiran, \{James E.D.\}",

note = "Publisher Copyright: {\textcopyright} 2019 Crown copyright.",

year = "2019",

month = sep,

day = "1",

doi = "10.1084/jem.20190344",

language = "English",

volume = "216",

pages = "1986--1998",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

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Spencer, S, Bal, SK, Egner, W, Allen, HL, Raza, SI, Ma, CA, Gürel, M, Zhang, Y, Sun, G, Sabroe, RA, Greene, D, Rae, W, Shahin, T, Kania, K, Ardy, RC, Thian, M, Staples, E, Pecchia-Bekkum, A, Worrall, WPM, Stephens, J, Brown, M, Tuna, S, York, M, Shackley, F, Kerrin, D, Sargur, R, Condliffe, A, Tipu, HN, Kuehn, HS, Rosenzweig, SD, Turro, E, Tavaré, S, Thrasher, AJ, Jodrell, DI, Smith, KGC, Boztug, K, Milner, JD & Thaventhiran, JED 2019, 'Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses', Journal of Experimental Medicine, vol. 216, no. 9, pp. 1986-1998. https://doi.org/10.1084/jem.20190344

TY - JOUR

T1 - Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

AU - Spencer, Sarah

AU - Bal, Sevgi Köstel

AU - Egner, William

AU - Allen, Hana Lango

AU - Raza, Syed I.

AU - Ma, Chi A.

AU - Gürel, Meltem

AU - Zhang, Yuan

AU - Sun, Guangping

AU - Sabroe, Ruth A.

AU - Greene, Daniel

AU - Rae, William

AU - Shahin, Tala

AU - Kania, Katarzyna

AU - Ardy, Rico Chandra

AU - Thian, Marini

AU - Staples, Emily

AU - Pecchia-Bekkum, Annika

AU - Worrall, William P.M.

AU - Stephens, Jonathan

AU - Brown, Matthew

AU - Tuna, Salih

AU - York, Melanie

AU - Shackley, Fiona

AU - Kerrin, Diarmuid

AU - Sargur, Ravishankar

AU - Condliffe, Alison

AU - Tipu, Hamid Nawaz

AU - Kuehn, Hye Sun

AU - Rosenzweig, Sergio D.

AU - Turro, Ernest

AU - Tavaré, Simon

AU - Thrasher, Adrian J.

AU - Jodrell, Duncan Ian

AU - Smith, Kenneth G.C.

AU - Boztug, Kaan

AU - Milner, Joshua D.

AU - Thaventhiran, James E.D.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.

AB - IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R. We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.

UR - https://www.scopus.com/pages/publications/85071783421

U2 - 10.1084/jem.20190344

DO - 10.1084/jem.20190344

M3 - Article

C2 - 31235509

AN - SCOPUS:85071783421

SN - 0022-1007

VL - 216

SP - 1986

EP - 1998

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 9

ER -

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses

Abstract

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