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

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


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 languageEnglish
Pages (from-to)1986-1998
Number of pages13
JournalJournal of Experimental Medicine
Issue number9
StatePublished - 1 Sep 2019
Externally publishedYes


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