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

Spencer et al. report the first description of human IL-6R deficiency in two patients presenting with recurrent infections, atopy, elevated IgE, and abnormal acute-phase responses.
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.