A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis.
Tobias Schwerd,Twigg Srf.,Dominik Aschenbrenner,S Manrique,Kerry A. Miller,Indira B. Taylor,Melania Capitani,Simon J. McGowan,E Sweeney,Astrid Weber,L Chen,Paul Bowness,A Riordan,Andrew J. Cant,Alexandra F. Freeman,Joshua D. Milner,Steve M. Holland,N Frede,Miryam Müller,Dirk Schmidt-Arras,Bodo Grimbacher,Bodo Grimbacher,Steven A. Wall,E Y Jones,Wilkie Aom.,Holm H. Uhlig +25 more
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TLDR
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 is identified with a novel immunodeficiency with phenotypic similarities to STAT3 hyper-IgE syndrome caused by loss of function of GP130.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.read more
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Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee
Stuart G. Tangye,Waleed Al-Herz,Aziz Bousfiha,Talal A. Chatila,Charlotte Cunningham-Rundles,Amos Etzioni,José Luis Franco,Steven M. Holland,Christoph Klein,Tomohiro Morio,Hans D. Ochs,Eric Oksenhendler,Capucine Picard,Jennifer M. Puck,Troy R. Torgerson,Jean-Laurent Casanova,Kathleen E. Sullivan +16 more
TL;DR: This report documents the key clinical and laboratory features of 430 inborn errors of immunity, including 64 gene defects that have either been discovered in the past 2 years since the previous update (published January 2018) or were characterized earlier but have since been confirmed or expanded upon in subsequent studies.
Journal ArticleDOI
Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines
TL;DR: The IL-6 family of cytokines in autoimmune diseases is reviewed from the viewpoints of their structure, signaling, and biological features and possible mechanisms of their functional pleiotropy are discussed.
Journal ArticleDOI
Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms.
Lloyd S. Miller,Vance G. Fowler,Sanjay K. Shukla,Sanjay K. Shukla,Warren E. Rose,Richard A. Proctor +5 more
TL;DR: The evidence presented form the basis for a hypothesis that staphylococcal toxins are important virulence factors, and targeting the neutralization of these toxins are more likely to provide a therapeutic benefit in contrast to prior vaccine attempts to generate antibodies to facilitate opsonophagocytosis.
Journal ArticleDOI
Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses.
Sarah Spencer,Sevgi Köstel Bal,William Egner,William Egner,Hana Lango Allen,Hana Lango Allen,Syed Irfan Raza,Chi Ma,Meltem Gürel,Yuan Zhang,Guangping Sun,Ruth A. Sabroe,Daniel Greene,Daniel Greene,William Rae,Tala Shahin,Katarzyna D. Kania,Rico Chandra Ardy,Marini Thian,Emily Staples,Annika Pecchia-Bekkum,William P.M. Worrall,Jonathan Stephens,Jonathan Stephens,Matthew A. Brown,Matthew A. Brown,Salih Tuna,Salih Tuna,Melanie York,Melanie York,Fiona Shackley,Fiona Shackley,Diarmuid Kerrin,Ravishankar Sargur,Ravishankar Sargur,Alison M. Condliffe,Alison M. Condliffe,Hamid Nawaz Tipu,Hye Sun Kuehn,Sergio D. Rosenzweig,Ernest Turro,Simon Tavaré,Simon Tavaré,Adrian J. Thrasher,Duncan I. Jodrell,Kenneth G. C. Smith,Kaan Boztug,Joshua D. Milner,James Thaventhiran +48 more
TL;DR: It is reported that this is the first description of human IL-6R deficiency in two patients presenting with recurrent infections, atopy, elevated IgE, and abnormal acute-phase responses.
Journal ArticleDOI
A recessive form of hyper-IgE syndrome by disruption of ZNF341-dependent STAT3 transcription and activity
Vivien Béziat,Vivien Béziat,Juan Li,Jian-Xin Lin,Cindy S. Ma,Cindy S. Ma,Peng Li,Aziz Bousfiha,Isabelle Pellier,Samaneh Zoghi,Samaneh Zoghi,Safa Baris,Sevgi Keles,Paul Gray,Paul Gray,Ning Du,Yi Wang,Yi Wang,Yoann Zerbib,Yoann Zerbib,Romain Lévy,Romain Lévy,Thibaut Leclercq,Thibaut Leclercq,Frédégonde About,Frédégonde About,Ai Ing Lim,Ai Ing Lim,Geetha Rao,Kathryn Payne,Simon J. Pelham,Simon J. Pelham,Danielle T. Avery,Elissa K. Deenick,Elissa K. Deenick,Bethany Pillay,Bethany Pillay,Janet Chou,Janet Chou,Romain Guery,Romain Guery,Aziz Belkadi,Aziz Belkadi,Antoine Guérin,Antoine Guérin,Mélanie Migaud,Mélanie Migaud,Vimel Rattina,Vimel Rattina,Fatima Ailal,Ibtihal Benhsaien,Matthieu Bouaziz,Matthieu Bouaziz,Tanwir Habib,Damien Chaussabel,Nico Marr,Jamel El-Benna,Bodo Grimbacher,Orli Wargon,Jacinta Bustamante,Bertrand Boisson,Bertrand Boisson,Bertrand Boisson,Ingrid Müller-Fleckenstein,Bernhard Fleckenstein,Marie-Olivia Chandesris,Matthias Titeux,Matthias Titeux,Sylvie Fraitag,Marie-Alexandra Alyanakian,Marianne Leruez-Ville,Capucine Picard,Isabelle Meyts,James P. Di Santo,James P. Di Santo,Alain Hovnanian,Alain Hovnanian,Ayper Somer,Ahmet Ozen,Nima Rezaei,Nima Rezaei,Talal A. Chatila,Talal A. Chatila,Laurent Abel,Laurent Abel,Laurent Abel,Warren J. Leonard,Stuart G. Tangye,Stuart G. Tangye,Anne Puel,Anne Puel,Anne Puel,Jean-Laurent Casanova +92 more
TL;DR: Patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 are described, revealing a Previously unappreciated layer of transcriptional regulation controlling JAK-STAT signaling.
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F. Ann Ran,Patrick D. Hsu,Jason Wright,Vineeta Agarwala,Vineeta Agarwala,David A. Scott,Feng Zhang +6 more
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Cem Gabay,Irving Kushner +1 more
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